Monoclonal antibodies obtained by Phage Display with FDA approval.
\r\n\t
",isbn:"978-1-83962-547-3",printIsbn:"978-1-83962-546-6",pdfIsbn:"978-1-83962-548-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"e5ba02fedd7c87f0ab66414f3b07de0c",bookSignature:" John P. Tiefenbacher",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10765.jpg",keywords:"Managing Urbanization, Managing Development, Managing Resource Use, Drought Management, Flood Management, Water Quality Monitoring, Air Quality Monitoring, Ecological Monitoring, Modeling Extreme Natural Events, Ecological Restoration, Restoring Environmental Flows, Environmental Management Perspectives",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 12th 2021",dateEndSecondStepPublish:"February 9th 2021",dateEndThirdStepPublish:"April 10th 2021",dateEndFourthStepPublish:"June 29th 2021",dateEndFifthStepPublish:"August 28th 2021",remainingDaysToSecondStep:"21 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"A geospatial scholar working at the interface of natural and human systems, collaborating internationally on innovative studies about hazards and environmental challenges. Dr. Tiefenbacher has published more than 200 papers on a diverse array of topics that examine perception and behaviors with regards to the application of pesticides, releases of toxic chemicals, environments of the U.S.-Mexico borderlands, wildlife hazards, and the geography of wine.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"73876",title:"Dr.",name:"John P.",middleName:null,surname:"Tiefenbacher",slug:"john-p.-tiefenbacher",fullName:"John P. Tiefenbacher",profilePictureURL:"https://mts.intechopen.com/storage/users/73876/images/system/73876.jfif",biography:"Dr. John P. Tiefenbacher (Ph.D., Rutgers, 1992) is a professor of Geography at Texas State University. His research has focused on various aspects of hazards and environmental management. Dr. Tiefenbacher has published on a diverse array of topics that examine perception and behaviors with regards to the application of pesticides, releases of toxic chemicals, environments of the U.S.-Mexico borderlands, wildlife hazards, and the geography of wine. More recently his work pertains to spatial adaptation to climate change, spatial responses in wine growing regions to climate change, the geographies of viticulture and wine, artificial intelligence and machine learning to predict patterns of natural processes and hazards, historical ethnic enclaves in American cities and regions, and environmental adaptations of 19th century European immigrants to North America's landscapes.",institutionString:"Texas State University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"Texas State University",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"12",title:"Environmental Sciences",slug:"environmental-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"194667",firstName:"Marijana",lastName:"Francetic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/194667/images/4752_n.jpg",email:"marijana@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"25894",title:"Production Scheduling on Practical Problems",doi:"10.5772/26319",slug:"production-scheduling-on-practical-problems",body:null,keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/25894.pdf",chapterXML:null,downloadPdfUrl:"/chapter/pdf-download/25894",previewPdfUrl:"/chapter/pdf-preview/25894",totalDownloads:10671,totalViews:176,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,dateSubmitted:"February 7th 2011",dateReviewed:"July 15th 2011",datePrePublished:null,datePublished:"January 11th 2012",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/25894",risUrl:"/chapter/ris/25894",book:{slug:"production-scheduling"},signatures:"Marcius Fabius Henriques de Carvalho and Rosana Beatriz Baptista Haddad",authors:[{id:"66222",title:"Dr.",name:"Rosana",middleName:"Beatriz",surname:"Haddad",fullName:"Rosana Haddad",slug:"rosana-haddad",email:"rosana.haddad@cti.gov.br",position:null,institution:{name:"Centro de Tecnologia da Informação Renato Archer",institutionURL:null,country:{name:"Brazil"}}},{id:"121008",title:"Dr.",name:"Marcius",middleName:null,surname:"Carvalho",fullName:"Marcius Carvalho",slug:"marcius-carvalho",email:"marcius.carvalho@pq.cnpq.br",position:null,institution:{name:"Pontifícia Universidade Católica de Campinas",institutionURL:null,country:{name:"Brazil"}}}],sections:null,chapterReferences:null,footnotes:null,contributors:null,corrections:null},book:{id:"883",title:"Production Scheduling",subtitle:null,fullTitle:"Production Scheduling",slug:"production-scheduling",publishedDate:"January 11th 2012",bookSignature:"Rodrigo da Rosa Righi",coverURL:"https://cdn.intechopen.com/books/images_new/883.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"69889",title:"Prof.",name:"Rodrigo",middleName:"Da Rosa",surname:"Righi",slug:"rodrigo-righi",fullName:"Rodrigo Righi"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"25887",title:"Process Rescheduling in High Performance Computing Environments",slug:"process-rescheduling-in-high-performance-computing-environments",totalDownloads:1721,totalCrossrefCites:0,signatures:"Rodrigo da Rosa Righi and Lucas Graebin",authors:[{id:"69889",title:"Prof.",name:"Rodrigo",middleName:"Da Rosa",surname:"Righi",fullName:"Rodrigo Righi",slug:"rodrigo-righi"},{id:"122097",title:"Dr.",name:"Arthur",middleName:null,surname:"Gomez",fullName:"Arthur Gomez",slug:"arthur-gomez"}]},{id:"25888",title:"Online Production Scheduling and Re-Scheduling in Autonomous, Intelligent Distributed Environments",slug:"online-production-scheduling-and-re-scheduling-in-autonomous-intelligent-distributed-environments",totalDownloads:1570,totalCrossrefCites:0,signatures:"Edgar Chacón, Juan Cardillo, Rafael Chacón and Germán Darío Zapata",authors:[{id:"11581",title:"Dr.",name:"Edgar",middleName:null,surname:"Chacón",fullName:"Edgar Chacón",slug:"edgar-chacon"},{id:"12410",title:"Prof.",name:"German",middleName:null,surname:"Zapata",fullName:"German Zapata",slug:"german-zapata"},{id:"75346",title:"Dr.",name:"Juan",middleName:null,surname:"Cardillo",fullName:"Juan Cardillo",slug:"juan-cardillo"},{id:"75353",title:"MSc.",name:"Rafael",middleName:null,surname:"Chacon",fullName:"Rafael Chacon",slug:"rafael-chacon"}]},{id:"25889",title:"Minimizing Makespan in Flow Shop Scheduling Using a Network Approach",slug:"minimizing-makespan-in-flow-shop-scheduling-using-a-network-approach",totalDownloads:4361,totalCrossrefCites:0,signatures:"Amin Sahraeian",authors:[{id:"118784",title:"MSc.",name:"Amin",middleName:null,surname:"Sahraeian",fullName:"Amin Sahraeian",slug:"amin-sahraeian"}]},{id:"25890",title:"Lot Processing in Hybrid Flow Shop Scheduling Problem",slug:"lot-processing-in-hybrid-flow-shop-scheduling-problem",totalDownloads:2818,totalCrossrefCites:1,signatures:"Larysa Burtseva, Rainier Romero, Salvador Ramirez, Victor Yaurima, Félix F. González-Navarro and Pedro Flores Perez",authors:[{id:"11073",title:"Dr",name:"Larysa",middleName:null,surname:"Burtseva",fullName:"Larysa Burtseva",slug:"larysa-burtseva"},{id:"11489",title:"Dr.",name:"Victor",middleName:"Hugo",surname:"Yaurima-Basaldua",fullName:"Victor Yaurima-Basaldua",slug:"victor-yaurima-basaldua"},{id:"40949",title:"MSc.",name:"Rainier",middleName:null,surname:"Romero",fullName:"Rainier Romero",slug:"rainier-romero"},{id:"40950",title:"BSc.",name:"Salvador",middleName:null,surname:"Ramirez",fullName:"Salvador Ramirez",slug:"salvador-ramirez"},{id:"108502",title:"Dr.",name:"Pedro",middleName:null,surname:"Flores",fullName:"Pedro Flores",slug:"pedro-flores"},{id:"115722",title:"Dr.",name:"Félix F.",middleName:null,surname:"González-Navarro",fullName:"Félix F. González-Navarro",slug:"felix-f.-gonzalez-navarro"}]},{id:"25891",title:"Analyzing Different Production Times Applied to the Job Shop Scheduling Problem",slug:"analyzing-different-production-times-applied-to-the-job-shop-scheduling-problem",totalDownloads:1950,totalCrossrefCites:0,signatures:"Arthur Tórgo Gómez, Antonio Gabriel Rodrigues and Rodrigo da Rosa Righi",authors:[{id:"69889",title:"Prof.",name:"Rodrigo",middleName:"Da Rosa",surname:"Righi",fullName:"Rodrigo Righi",slug:"rodrigo-righi"},{id:"122097",title:"Dr.",name:"Arthur",middleName:null,surname:"Gomez",fullName:"Arthur Gomez",slug:"arthur-gomez"},{id:"127211",title:"MSc.",name:"Antonio",middleName:null,surname:"Rodrigues",fullName:"Antonio Rodrigues",slug:"antonio-rodrigues"}]},{id:"25892",title:"Adaptive Production Scheduling and Control in One-Of-A-Kind Production",slug:"adaptive-production-scheduling-and-control-in-one-of-a-kind-production",totalDownloads:1518,totalCrossrefCites:1,signatures:"Wei Li and Yiliu Tu",authors:[{id:"67772",title:"Dr.",name:null,middleName:null,surname:"Tu",fullName:"Tu",slug:"tu"},{id:"73805",title:"Dr.",name:"Wei",middleName:null,surname:"Li",fullName:"Wei Li",slug:"wei-li"}]},{id:"25893",title:"Simulation-Based Modular Scheduling System of Semiconductor Manufacturing",slug:"simulation-based-modular-scheduling-system-of-semiconductor-manufacturing",totalDownloads:3104,totalCrossrefCites:3,signatures:"Li Li, Qiao Fei Ma Yumin and Ye Kai",authors:[{id:"11038",title:"Dr.",name:"Li",middleName:null,surname:"Li",fullName:"Li Li",slug:"li-li"}]},{id:"25894",title:"Production Scheduling on Practical Problems",slug:"production-scheduling-on-practical-problems",totalDownloads:10671,totalCrossrefCites:1,signatures:"Marcius Fabius Henriques de Carvalho and Rosana Beatriz Baptista Haddad",authors:[{id:"66222",title:"Dr.",name:"Rosana",middleName:"Beatriz",surname:"Haddad",fullName:"Rosana Haddad",slug:"rosana-haddad"},{id:"121008",title:"Dr.",name:"Marcius",middleName:null,surname:"Carvalho",fullName:"Marcius Carvalho",slug:"marcius-carvalho"}]},{id:"25895",title:"Achieving Cost Competitiveness with an Agent-Based Integrated Process Planning and Production Scheduling System",slug:"achieving-cost-competitiveness-with-an-agent-based-integrated-process-planning-and-production-schedu",totalDownloads:1298,totalCrossrefCites:0,signatures:"Ming Lim and David Zhang",authors:[{id:"64872",title:"Dr.",name:"Ming",middleName:"K",surname:"Lim",fullName:"Ming Lim",slug:"ming-lim"},{id:"114743",title:"Prof.",name:"David",middleName:null,surname:"Zhang",fullName:"David Zhang",slug:"david-zhang"}]},{id:"25896",title:"Using Timed Coloured Petri Nets for Modelling, Simulation and Scheduling of Production Systems",slug:"using-timed-coloured-petri-nets-for-modelling-simulation-and-scheduling-of-production-systems",totalDownloads:3239,totalCrossrefCites:3,signatures:"Andrzej Bozek",authors:[{id:"65177",title:"MSc.",name:"Andrzej",middleName:null,surname:"Bozek",fullName:"Andrzej Bozek",slug:"andrzej-bozek"}]}]},relatedBooks:[{type:"book",id:"8754",title:"Scheduling Problems",subtitle:"New Applications and Trends",isOpenForSubmission:!1,hash:"c700a7e3dbf7482d7d82a1e6639b7f32",slug:"scheduling-problems-new-applications-and-trends",bookSignature:"Rodrigo da Rosa Righi",coverURL:"https://cdn.intechopen.com/books/images_new/8754.jpg",editedByType:"Edited by",editors:[{id:"69889",title:"Prof.",name:"Rodrigo",surname:"Righi",slug:"rodrigo-righi",fullName:"Rodrigo Righi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"67033",title:"Global Optimization Using Local Search Approach for Course Scheduling Problem",slug:"global-optimization-using-local-search-approach-for-course-scheduling-problem",signatures:"Ade Jamal",authors:[{id:"292309",title:"Dr.",name:"Ade",middleName:null,surname:"Jamal",fullName:"Ade Jamal",slug:"ade-jamal"}]},{id:"67906",title:"Real-Time Scheduling Method for Middleware of Industrial Automation Devices",slug:"real-time-scheduling-method-for-middleware-of-industrial-automation-devices",signatures:"Hong Seong Park",authors:[{id:"110782",title:"Prof.",name:"Hong Seong",middleName:null,surname:"Park",fullName:"Hong Seong Park",slug:"hong-seong-park"}]},{id:"68147",title:"Intelligent Workload Scheduling in Distributed Computing Environment for Balance between Energy Efficiency and Performance",slug:"intelligent-workload-scheduling-in-distributed-computing-environment-for-balance-between-energy-effi",signatures:"Larysa Globa, Oleksandr Stryzhak, Nataliia Gvozdetska and Volodymyr Prokopets",authors:[{id:"105085",title:"Prof.",name:"Larysa",middleName:null,surname:"Globa",fullName:"Larysa Globa",slug:"larysa-globa"},{id:"219896",title:"Prof.",name:"Alexander",middleName:null,surname:"Koval",fullName:"Alexander Koval",slug:"alexander-koval"},{id:"296047",title:"Ms.",name:"Nataliia",middleName:null,surname:"Gvozdetska",fullName:"Nataliia Gvozdetska",slug:"nataliia-gvozdetska"},{id:"296048",title:"Mr.",name:"Volodymyr",middleName:null,surname:"Prokopets",fullName:"Volodymyr Prokopets",slug:"volodymyr-prokopets"}]},{id:"70290",title:"Approximation for Scheduling on Parallel Machines with Fixed Jobs or Unavailability Periods",slug:"approximation-for-scheduling-on-parallel-machines-with-fixed-jobs-or-unavailability-periods",signatures:"Liliana Grigoriu",authors:[{id:"293390",title:"Dr.",name:"Liliana",middleName:null,surname:"Grigoriu",fullName:"Liliana Grigoriu",slug:"liliana-grigoriu"}]},{id:"71826",title:"An Empirical Survey on Load Balancing: A Nature-Inspired Approach",slug:"an-empirical-survey-on-load-balancing-a-nature-inspired-approach",signatures:"Surya Teja Marella and Thummuru Gunasekhar",authors:[{id:"297632",title:"Mr.",name:"Surya Teja",middleName:null,surname:"Marella",fullName:"Surya Teja Marella",slug:"surya-teja-marella"},{id:"298899",title:"Dr.",name:"Thummuru",middleName:null,surname:"Gunasekhar",fullName:"Thummuru Gunasekhar",slug:"thummuru-gunasekhar"}]},{id:"72346",title:"Looking at Data Science through the Lens of Scheduling and Load Balancing",slug:"looking-at-data-science-through-the-lens-of-scheduling-and-load-balancing",signatures:"Diórgenes Eugênio da Silveira, Eduardo Souza dos Reis, Rodrigo Simon Bavaresco, Marcio Miguel Gomes, Cristiano André da Costa, Jorge Luis Victoria Barbosa, Rodolfo Stoffel Antunes, Alvaro Machado Júnior, Rodrigo Saad and Rodrigo da Rosa Righi",authors:[{id:"69889",title:"Prof.",name:"Rodrigo",middleName:"Da Rosa",surname:"Righi",fullName:"Rodrigo Righi",slug:"rodrigo-righi"},{id:"18257",title:"Dr.",name:"Cristiano",middleName:null,surname:"Costa",fullName:"Cristiano Costa",slug:"cristiano-costa"},{id:"321638",title:"Dr.",name:"Diorgenes Eugenio",middleName:null,surname:"da Silveira",fullName:"Diorgenes Eugenio da Silveira",slug:"diorgenes-eugenio-da-silveira"},{id:"321639",title:"Dr.",name:"Jorge Luis",middleName:null,surname:"Barbosa",fullName:"Jorge Luis Barbosa",slug:"jorge-luis-barbosa"},{id:"321640",title:"Dr.",name:"Rodolfo Stoffel",middleName:null,surname:"Antunes",fullName:"Rodolfo Stoffel Antunes",slug:"rodolfo-stoffel-antunes"},{id:"321641",title:"Dr.",name:"Eduardo",middleName:null,surname:"Souza dos Reis",fullName:"Eduardo Souza dos Reis",slug:"eduardo-souza-dos-reis"},{id:"321642",title:"M.Sc.",name:"Marcio",middleName:"Miguel",surname:"Gomes",fullName:"Marcio Gomes",slug:"marcio-gomes"},{id:"321643",title:"Dr.",name:"Rodrigo Simon",middleName:null,surname:"Bavaresco",fullName:"Rodrigo Simon Bavaresco",slug:"rodrigo-simon-bavaresco"},{id:"322136",title:"Dr.",name:"Rodrigo",middleName:null,surname:"Saad",fullName:"Rodrigo Saad",slug:"rodrigo-saad"},{id:"322137",title:"Dr.",name:"Alvaro",middleName:null,surname:"Machado Júnior",fullName:"Alvaro Machado Júnior",slug:"alvaro-machado-junior"}]},{id:"71902",title:"Types of Task Scheduling Algorithms in Cloud Computing Environment",slug:"types-of-task-scheduling-algorithms-in-cloud-computing-environment",signatures:"Tahani Aladwani",authors:[{id:"291371",title:"M.Sc.",name:"Tahani",middleName:null,surname:"Aladwani",fullName:"Tahani Aladwani",slug:"tahani-aladwani"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"72681",title:"Phage Display as a Strategy to Obtain Anti-flavivirus Monoclonal Antibodies",doi:"10.5772/intechopen.93076",slug:"phage-display-as-a-strategy-to-obtain-anti-flavivirus-monoclonal-antibodies",body:'\nWhen thinking about the development of virus detection and neutralization technologies whose bases of action are immunoglobulins, it is necessary to understand the structure of the viral particle of interest. In addition to the sequence of amino acid residues that make up the target epitopes, their position in the particle and their function in the process of infection and viral replication influence the design experiments aiming the obtantion of antibodies with a diagnostic and therapeutic potential.
\nThe structures of flavivirus have been determined and studied, mainly, by combining cryo-electron microscopy with data from X-ray diffraction experiments using crystallography of viral proteins in the presence or not of antibody molecules. Results of this combination showed that the flavivirus is composed of a dense icosahedral electron nucleus and a lipid bilayer surrounding it. The genome comprises a sequence of ~10,700 nucleotides of a positive-sense RNA that encodes a polyprotein that is cleaved in 3 structural proteins, capsid protein (C), membrane protein (M), and envelope protein (E), and in 7 nonstructural proteins, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 [1]. The NS1 protein plays a role in viral replication and is often shown to be a soluble antigen secreted into the bloodstream, interacting with components of the immune system. NS5 is the largest and most conserved nonstructural protein and acts in the transcription process of viral RNA [2, 3].
\nThe icosahedral capsid is small and poorly organized, but it provides enough space for the genome and is surrounded by the envelope, so there are few connections between these structures, unlike what is found in other viruses. The viral envelope consists of two internal and concentric layers of phospholipids and an outer protein shell formed by regions of protein M and ectodomains of glycoprotein E organized in dimers which present protein determinants for the binding of the virus to the host cell (hemagglutination). Protein E contains three domains: domain I (DI), which is related to cell tropism and envelope organization; domain II (DII), which comprises the dimerization region and the fusion peptide; and domain III (DIII) with the function of binding to cell receptors, in the initial stage of viral infection [4, 5].
\nThe fusion loop is a highly conserved region between dengue virus (DENV) serotypes and all flaviviruses, responsible for the late stage of infection, in which the virus interacts with the endosomal membrane, resulting in the release of the nucleocapsid in the cytoplasm. When the particle is in the lysosomal vesicle during the infection process, a structural reorganization of the viral envelope occurs; the fusion loop is exposed and inserted in the lysosomal membrane. After the formation of the fusion loop contact, protein E starts to organize itself into trimmers, resulting in the expansion of the viral particle and the approximation of the viral and lysosomal membranes, forming the fusion lipid pore that allows the release of the viral genome to the cytoplasm [3, 6, 7].
\nDENV serotypes show great heterogeneity in the structure of viral proteins. However, there is also antigenic similarity between DENV serotypes and, for some peptide sequences, between flaviviruses. Phylogeny studies of virus sequences, by estimating the antigenic distance between them, concluded that serotypes 1 and 3 are the most similar, serotype 2 was the second to diverge evolutionarily, and serotype 4 is the one that presents greater genetic difference. There is a 32% difference in the structure of protein E of the four DENV serotypes. Specific mutations in the genome result in the antigenic variability found in each serotype [7, 8, 9].
\nMuch of the genetic difference between flaviviruses is due to protein E, which can show up to 60% difference in its amino acid sequence. In the phylogenetic analysis of the viruses, the DENV serotypes are closer to the Zika virus (ZIKV), with approximately 45% difference, and have 50 and 60% dissimilarity with West Nile virus (WNV) and yellow fever virus (YFV), respectively. DENV and other flaviviruses vary dramatically in terms of the amino acid sequence of the glycosylation region and the content of glycans added to the surface of E and precursor membrane protein (prM). Many epitopes of protein E are unique to a DENV serotype [4, 9, 10, 11]. It can also be observed in ZIKV, which has the glycosylation site, in the DI of protein E, different in conformation and length of the loop that contains this glycosylation site. The carbohydrate associated with this residue can act as a virus binding site in host cells. Thus, differences in this region of glycosylation can influence cell tropism, infection, and pathogenesis of these viruses [12]. Another important characteristic of ZIKV is the insertion of an alanine residue in the carboxyl termination of DIII, which is associated with an increased stability of this virus [13].
\nThe hydrophobic sequence of the fusion loop appears to be the only epitope that is conserved among all flaviviruses; however, the degree of exposure in this region varies substantially among viruses [6]. Nonstructural proteins, NS1 and NS5, also present some epitopes conserved among the DENV serotypes and other members of the flavivirus genus, but their position also varies between viral strains. The relationships of antigenic similarity between flaviviruses generate immune responses that are configured as cross-reactions with protective or pathological characteristics [5, 14, 15].
\nImmunoglobulins, or antibodies, are glycoproteins, expressed on the surface of B cells or secreted, that act in the neutralization and elimination of pathogens [16]. Antibodies are relatively flexible “Y”-shaped molecules made up of two heavy chains and two light chains, joined by an extensive network of non-covalent interactions, stabilized by disulfide bonds. Both types of chains are composed of constant and variable domains. The constant regions determine the functional properties of the antibody, and the variable regions determine the antigen-binding site. The light chain consists of a variable portion (VL) and a constant portion (CL) that can have two types of domains, kappa (ƙ) or lambda (λ). The heavy chain consists of a variable portion (VH) and three or four constant portions, depending on the class of the antibody, which are CH1, CH2, CH3, and CH4. The type of heavy chain determines the class, or isotype, of antibody, such as IgA, IgG, IgD, IgE, and IgM [17].
\nThe antibody molecule can be subdivided into portions of the crystallizable fragment (Fc) and antigen-binding fragment (Fab) region. The Fc portion has the constant domains (CH2, CH3, CH4), and the Fab portion consists of the VH-CH1 and VL-CL domains. The Fab portion retains the ability to bind to the antigen, and the Fc portion acts to mediate the effector functions of antibodies [17].
\nThree segments containing variability can be identified in both the VH and VL domains. These segments are the hypervariable regions that determine antigen specificity and are more commonly called complementarity-determining regions (CDRs)—CDR1, CDR2, and CDR3. The combination of CDRs from a VH with CDRs from a VL forms the region of interaction with the epitope, called the paratope [17]. The variability of the antigen-binding regions is responsible for the ability of different antibodies to bind to many structurally diverse antigens [18]. Figure 1 represents the structure of an IgG immunoglobulin and its domains.
\nClassical structure of an antibody. Structure of a class G immunoglobulin, representing the two portions of the molecule: two Fabs that correspond to the antigen-binding fragment and an Fc that corresponds to the crystallizable fragment. A type G antibody consists of two heavy polypeptide chains, each containing a VH and three constant domains (CH1, CH2, and CH3), and two light chains, each containing a VL and a CL. CDRs are three regions of hypervariability present in each of the variable domains. In addition to the natural format of the antibody, it is possible to generate recombinant antibodies such as the single-chain variable fragment (scFvs).
In cognate antigen recognition, some naïve B cells can initiate somatic hypermutation, generating new variable domains, that can be selected based on their ability of antigen binding, usually with high affinity compared to germinal domains. After antigen recognition, naïve B cells differentiate into antibody-secreting plasma cells. These plasma cells secrete antibodies with high affinity and, can differentiate into memory B cells. Memory B cells are highly specialized cells for quickly recognizing the antigen in subsequent exposure, can persist for years, and provide long-term humoral protection for decades. These functional features of memory B cells are the basis of effective vaccines [19].
\nThe knowledge about the mechanisms of antibody production and clonal selection of B cells led to the development of innovative hybridoma technology in 1975 [20]. The technique is based on the fusion of B lymphocytes with myeloma cells giving rise to hybrid cells that produce monoclonal antibodies (MAbs) continuously in vitro [21]. Therefore, MAbs are monovalent antibodies, which bind to the same epitope and are produced from a single B lymphocyte clone.
\nMAbs interact with a single epitope allowing a specific reactivity and affinity for target antigens. This feature is a great advantage over polyclonal antibodies, which have different epitope specificities and affinities [22, 23]. For this reason, MAbs have a broad clinical applicability in therapy for various illness, including cancer, transplant rejection, and autoimmune, infectious, hematologic, and cardiovascular diseases. Moreover, MAbs can play a significant role in the diagnosis and as antibody-drug conjugate for drug delivery. Thus, MAbs are considered a powerful tool for a wide range of medical applications.
\nAntibodies that bind to different flaviviruses are able to promote both the neutralization of the infection and the increase of the virus capture, such as by the interaction of immune complexes with Fc receptors expressed in certain cell types. The creation of alternative routes of entry of the viral particle into cells by low-neutralizing antibodies, during secondary infections of flavivirus, results in increased levels of viral replication and pathogenicity. This mechanism constitutes a phenomenon called antibody-dependent enhancement (ADE) [24, 25].
\nDifferent studies have been conducted to understand the effects of cross-reactive memory antibodies on subsequent flavivirus exposures. Many of them reported that the opsonization of the virus with weakly neutralizing antibodies led to the increase of the viral production and of pro-inflammatory mediators. This could lead to the suppression of the antiviral immune response, worsening the clinical condition of the disease [5, 7]. ADE has already been reported in in vitro experiments of infection of cells that express Fc receptors and in vivo experiments of vaccination with flavivirus [11, 26]. From the results of these experiments, ADE is pointed out as one of the main causes of severe forms of DENV infection and of the low protection induced by vaccines targeting DENV serotypes [27].
\nAn opposite effect of cross-reacting antibodies has also been demonstrated, an increase in protection against secondary infections by flavivirus, which has resulted in potent neutralization and rapid induction of affinity maturing immune responses against heterologous flaviviruses. Studies in endemic areas of flavivirus showed protection against Zika virus infection in patients with a previous experience with DENV. A humoral response capable of potentially neutralizing both species of flavivirus was assembled from the expansion of cross-reaction memory B cell clones, even in the absence of DENV circulation. Thus, previous flavivirus infections can lead to both cross-neutralization and increased pathogenicity of the virus through the formation of interspecific antibody memory [28, 29].
\nThe potential of cross-reaction immunity to trigger protection or pathology depends on the profile, quality, and magnitude of the immune responses induced by antibodies. The ADE reaction is a factor that should be considered in the development of therapeutic antibodies and vaccines for infections by flavivirus. Different approaches have been tested to shift the ADE profile to a cross-protection profile in heterogeneous infections of these viruses.
\nThe principle of the Phage Display is the presentation of libraries of molecules on the surface of a bacteriophage (phage), allowing the identification of a wide range of biomolecules, including peptides, antibodies, and other proteins. The Phage Display methodology was first described in 1985, by George Smith and colleagues. Through the expression (display) of polypeptides on the phage surface (phage) M13, it was possible to perform the mapping of antibody epitopes by screening them using random peptide libraries [30]. In 1990, McCafferty and colleagues [31] demonstrated that it was also possible to fuse genes that encode an entire antibody domain, in the form of a scFv to the sequence of one of the bacteriophage’s coat proteins. This approach allowed that this methodology could also be used for the selection of bacteriophages that recognize antigens.
\nLater, in 1994, Winter refined the Phage Display technology through a guided selection strategy of human antibody fragments from Phage Display repertoires for a single-antigen epitope, using rodent MAbs as a model [32]. The first all-human antibody produced, using Winter’s Phage Display technique, to be marketed for use in humans was adalimumab (Humira), approved by the United States Food and Drug Administration (FDA) in 2002 for the treatment of rheumatoid arthritis [33]. It is noteworthy that George P. Smith and Gregory P. Winter received the Nobel Prize in chemistry in 2018 for the Phage Display of peptides and antibodies (Nobel Prize, 2018), a true tool for molecular evolution in vitro emphasizing the importance of this technique in obtaining biomolecules for various applications.
\nPhages are single-stranded viruses that infect Gram-negative bacteria and are used mainly for the purpose of gene cloning and expression of recombinant proteins, in addition to basic molecular biology studies. The particle coating is composed of five different proteins, pIII, pVI, pVII, pVIII, and pIX; proteins responsible for DNA replication include pII, pV, and pX; and the assembly proteins are pI, pIV, and pXI. All of the five proteins contribute to the stability of the phage particle; however, pIII is also necessary for the recognition and infection of the host cell [33]. Through genetic manipulation, sequences of billions of peptides, protein variants, and antibody fragments can be cloned into a vector associated with the phage coat protein gene, the pIII protein being the most commonly used [34]. Thus, the Phage Display methodology explores the possibility of direct binding of a certain protein (phenotype) with its cognate gene (genotype) by means of a phage [35].
\nBeyond the Phage Display and hybridoma technique, other strategies used for MAb production include immortalization of human B lymphocyte isolated from naturally infected or immunized individuals. One of the approaches for B lymphocyte immortalization is using Epstein-Barr virus (EBV). EBV is a human tumor virus that was shown to infect efficiently human B lymphocytes and induce continuous proliferation in vitro, opening a new perspective for the production of human MAbs [36]. Another relevant alternative for MAb production involves transgenic animals where mice are genetically manipulated to produce human immunoglobulin. In this strategy, genes of human immunoglobulins are inserted into mice genome replacing the endogenous sequences, making these animals capable to produce fully human antibodies when immunized with an antigen [37].
\nAmong the existing methodologies of antibody production, the hybridoma technique remains the most widely used. However, the production steps are laborious and dependent on the animal immune system. In addition, the heterologous character of these proteins often makes them immunogenic to humans, provoking the response of human anti-mouse antibodies (HAMA), which restrict their therapeutic use [34]. Therefore, the Phage Display has emerged as one of the main alternatives for the generation of human recombinant MAbs. The major advantages of using the Phage Display, in contrast to the hybridoma technique, are clearly the absence of the use of animals in the process and the less time to obtain antibodies. The conventional method requires immunization which, depending on the type of antigen, can take weeks to produce sufficient immune response to produce specific antibodies [38].
\nThere are important advantages and disadvantages between techniques for obtaining human MAbs. With the Phage Display technology, it is possible to isolate antibodies against all types of antigens, even those with high complexity; differently, the immortalization technique of human lymphocytes does not allow the isolation of antibodies against own antigens or non-immunogenic antigens [39]. In addition, only the Phage Display allows the optimization of MAbs, for example, by affinity maturation, and in general, the development of antibodies on the Phage Display tends to be faster than in other methods [40].
\nIn addition to being robust due to the high stability of the phage, the Phage Display also allows control over biochemical parameters throughout the selection process. The particular advantage of having control over biochemical parameters during the time of selection can also be used to shape the specificity profile of an antibody from the start [41]. Table 1 described the MAbs with FDA approval that was developed using the Phage Display technique.
\nAntibody | \nTarget | \nFormat | \nIndication | \nCompany | \nYear | \n
---|---|---|---|---|---|
Humira adalimumab | \nTNF-α | \nHuman | \nRheumatoid arthritis and Crohn’s disease | \nAbbott | \n2002 | \n
Lucentis Ranibizumab | \nVEGF-A | \nHumanized | \nMacular degeneration | \nGenentech | \n2006 | \n
Simponi Golimumab | \nTNF-α | \nHuman | \nRheumatoid arthritis | \nJohnson & Johnson | \n2009 | \n
Benlysta Belimumab | \nBLys | \nHuman | \nSystemic lupus erythematosus | \nGSK | \n2011 | \n
Pending Raxibacumab | \nPA | \nHuman | \nAnthrax infection (Bacillus anthracis) | \nGSK | \n2012 | \n
Cyramza Ramucirumab | \nVEGFR2 | \nHuman | \nGastric cancer | \nLilly | \n2014 | \n
Bavencio Avelumab | \nPD-L1 | \nHuman | \nMerkel cell carcinoma | \nSerono | \n2017 | \n
Tremfya Guselkumab | \nIL-23 | \nHuman | \nPlaque psoriasis | \nJanssen Biotech | \n2017 | \n
Gamifant Emapalumab | \nIFNγ | \nHuman | \nHemophagocytic lymphohistiocytosis | \nSwiss | \n2018 | \n
Monoclonal antibodies obtained by Phage Display with FDA approval.
TNF-α, tumor necrosis factor alpha; VEGF-A, vascular endothelial growth factor A; BLys, B lymphocyte stimulator; PA, protective antigen; VEGFR2, vascular endothelial growth factor receptor 2; PD-L1, programmed death-ligand 1; IL-23, interleukin-23; IFNγ, interferon-γ
Since 1990, different antibody formats have been employed in the construction of antibody Phage Display libraries (APDLs). Although antibody libraries are one of the most successful tools of Phage Display, the appropriate choice of antibody library is an important step for the success of antibody selection. Full-length antibodies in the immunoglobulin format are large (150 kDa), complex, and not suitable for Phage Display. Therefore, smaller antigen-binding fragments are used. For this reason, APDLs are in most cases constructed in either scFv (25 kDa), Fab (50 kDa), or single-domain antibody (sdAb) formats which are smaller and more effective, although each antibody format has its own advantages and limitations [42]. Particularly, sdAbs have received a growing interest as a promising antibody class compared with those conventional. Their more hydrophilic structure, easy molecular manipulation, convex surface, and long CDRs enable them to recognize cryptic and inaccessible epitopes for typical antibody fragments [43].
\nThere are many kinds of APDLs; they can be classified into two main types: natural APDL and synthetic APDL. This classification is based on the source of VH and VL genes. Natural APDL comprises immune libraries and naïve libraries, while synthetic APDLs comprise semisynthetic libraries and fully synthetic libraries [44]. The immune libraries use V-genes that already passed to the clonal selection and encode antibodies with high affinity and specificity against the target antigen. The immune APDLs have some advantages compared to other libraries, once they have the possibility to be explored for understanding the humoral responses in the specific disease. However, some limitations regarding this library are associated with the toxicity of some antigens and some ethical issues, which consequently impair the feasibility to active immunization of humans or other animals for obtention of antibody repertoires [41, 44].
\nThe naïve APLD involves the generation of libraries that allows the discovery of MAbs against all types of antigen. These libraries are produced through the repertoires of healthy donors, and antibody genes contained have much more diversity than immune libraries. The main advantage of using naïve libraries is the possibility to isolate MAbs against non-immunogenic and toxic antigens. However, the major drawback is that the selected MAbs often have low affinities compared with antibodies from immune libraries [33]. The semisynthetic APLD is based on the display of artificially made diversity in V-gene segments, usually by in vitro randomization of CDRs from a limited number of naïve variable regions, reconstructing the V-gene repertoires [41]. One of the characteristics of these libraries is the absence of natural biases and redundancies usually found in a naïve library. Unlike semisynthetic APDLs, the fully synthetic library is constructed through the incorporation of nucleotide randomization based on in silico design and de novo synthesis. This refined synthesis appears to increase the functional size of library and consequently the isolation of MAbs with a great range of affinity. However, they still need to be optimized regarding their binding sites, affinity, valency, and other characteristics [41, 44].
\nExcept in the case of fully synthetic libraries, generally, the construction of an antibody library is based on the amplification of the repertoire of the variable chain genes of one or more individuals using primers that cover all families of this gene. Subsequently, a random combination of the VL and VH chain is generated. In the case of the production of Fab libraries, a step is taken to join each variable chain fragment with its respective constant region. The PCR products of these amplifications, representing the antibody repertoire, are ligated into a phagemid vector and transformed into E. coli. However, phage vectors generally have only the origin of replication of the phage; they do not contain all the genes necessary for replication and assembly of these phages. Thus, screening libraries using this phagemid requires a helper phage to provide replication and assembly proteins. The addition of the phage to the bacterial cells transformed with the phagemid will result in the production of a mixture of phages that will present predominantly the phagemid vector [45].
\nOnce assembled, each phage exposes a fragment of functional antibody fused to one of the phage surface proteins [46, 47]. A determining factor for the quality of a library and consequently the success of a biopanning by Phage Display is its initial diversity, given by the number of different antibodies in the library. The greater the initial diversity of clones within the library, the greater the likelihood of containing sequences that will bind to a given target with greater affinity [45]. The capacity to produce very large libraries (1012 different clones) has turned the Phage Display into a fast and reliable high-throughput screening methodology [43].
\nMost biopanning methods are based on four main steps, preparing a library; incubation of that library with a given antigen; removal of nonspecific or low-affinity phages; and recovery of binding targets, which will be amplified after infection in E. coli and used in the next biopanning cycle (Figure 2). The Phage Display biopanning process is characterized by an increase in the number of clones with affinity for the target molecule through successive selection cycles, with a consequent reduction in the diversity of clones and in the presence of clones with low affinity [48]. Thus, the biopanning results in the sequential enrichment of phages that have a specific binding to the antigen.
\nBiopanning steps. Representation of a biopanning process characterized by a step of Phage Display library incubation with the target antigen, removal of unbound phages, elution of bound phages, and phage amplification in E. coli, followed by another cycle. After 3–5 cycles post-selection step is carried out.
These biopanning steps are usually repeated three to five times, until a high specificity/affinity ligand is identified [34, 45, 46]. During biopanning, phage binding to the antigen is retained on the plate, and, after a series of washes, these phages are eluted and amplified. Subsequently, the phages are again incubated with the antigen in the next cycle. Phages with low affinity for antigens may stick to the plate, not interacting with the particle, or remain suspended in the solution. After the wash step, many of these nonspecific phages are removed. Generally, this step involves the application of a greater wash stringency in each subsequent round, which can be performed by increasing the number of washes or increasing the concentration of the nonionic detergent buffer used.
\nDuring the biopanning stage, it is possible to monitor the enrichment of antibodies by measuring the phage titers that enter the selection and the phage titers that are eluted, assessing the enrichment ratio at each selection cycle. The enrichment follow-up provides the assurance that the selection was carried out efficiently and is followed by the analysis of the selection progress and the identification of the antibodies that have greater affinity to the target antigen [49]. Over the decades, different ways of analyzing selection have been reported, depending on the selection system employed, the antibody library used, and the antigen of interest. However, two methods stand out for the quality of the results they offer, a monoclonal analysis of a sample of the selected antibodies and a polyclonal analysis of the sequences of the entire antibody population.
\nFrom the population of selected phages or using cultures of the selected soluble antibodies, the specific binding of individual clones to the immobilized antigen is assessed in an ELISA assay. In this monoclonal ELISA, the binding of 30–100, or more, randomly chosen clones is compared with each other and with the negative control. Phages with the highest absorbance values are considered the ones that have displayed functionally antibodies of greater affinity. Positive clones for the binding analysis are subjected to a Sanger sequencing reaction to determine the sequences of the antibodies [50, 51, 52]. In this type of Phage Display analysis, the phenotypes (activity) of the antibodies are investigated first and then their genotype is determined. The disadvantage of this type of analysis is that it does not allow exploring the antibody population in depth and may not include all antibodies of greater affinity. In addition, it does not allow the study of the magnitude of selection and enrichment [53].
\nA high-throughput sequencing provides a tool for rapid analysis of the selection and direct identification of the most enriched antibodies, with greater affinity, without requiring a step of their expression. In addition to the speed of analysis, it is possible to investigate the original diversity of the library; identify all antibodies that enriched, the most enriched, and the rare in the population; and determine the frequency of increase throughout the selection. This is possible because sequencing technologies, called next-generation sequencing (NGS), are used, and they allow sequencing a large number of sequences, in the order of millions, in the same sequencing reaction [54]. The interpretation of NGS results from antibody libraries requires the use of a bioinformatics tool specialized in calculating the enrichment of variable domains in a selection of Phage Display. Different tools for this purpose are described in the literature, such as the recent ATTILA pipeline [55].
\nDespite providing a profound assessment of all antibodies in all cycles, two major problems arise in the analysis of biopanning by sequencing. The first corresponds to the noise in the identified final sequences that results from the sequencing process or the gene amplification reaction. However, more accurate pipelines for isolating DNA libraries for sequencing and more powerful bioinformatics analysis programs have been produced to overcome the artifacts introduced by PCR and sequencing errors. The second is the limitation of the high-performance sequencing methodology that, although it allows the sequencing of millions of sequences, can only properly read up to 400 base pairs. Therefore, this analysis requires that the variable domains of the heavy and light chain of antibodies, whose size ranges from 300 to 400 base pairs, be amplified and sequenced separately, resulting in the loss of the VH and VL pairs of the most enriched antibodies. Recently, studies have been carried out to provide a method of sequencing without losing the VH and VL pairs of antibodies. In the analysis of the selection process by a high-throughput sequencing, the antibody’s genotype is first determined and then their phenotype is characterized [53, 56, 57].
\nThe use of MAbs against an infection pathogen is an area of great interest for research. In Table 2 it is demonstrated MAbs developed for infection disease who have been approved by the FDA. As can be seen, few MAbs are approved for use in infectious diseases, although there is still a strong demand for development in this field. Some challenges involving MAb production against pathogens are their economic viability due to their high cost and if target an episodic disease, there is no supporting for continued production. Moreover, there is a concern about the selection of neutralization-escape mutants [58]. However, they may be notably effective for certain emerging infectious diseases, in which the process of vaccine development could be lengthened and difficult. Thus, MAbs should have more effectiveness for the first response against these diseases [57].
\nAntibody | \nTarget | \nFormat | \nIndication | \nCompany | \nYear | \nMethod | \n|
---|---|---|---|---|---|---|---|
Pending Raxibacumab | \nPA | \nHuman | \nAnthrax infection (Bacillus anthracis) | \nGSK | \n2012 | \nPhage Display | \n|
Zinplava Bezlotoxumab | \nToxin B | \nHuman | \n\nClostridium difficile infection | \nMerck/Dohme | \n2016 | \nTransgenic mice | \n|
Trogarzo Ibalizumab | \nCD4 | \nHumanized | \nHIV infection | \nTaiMed | \n2018 | \nHybridoma | \n|
Synagis Palivizumab | \nRSV F | \nHumanized | \nRespiratory syncytial virus (RSV) prophylaxis | \nMedImmune | \n1998 | \nHybridoma | \n
Monoclonal antibodies for infectious diseases approved by the FDA.
PA, protective antigen; CD4, cluster of differentiation 4; RSV F, respiratory syncytial virus fusion
Small molecules are most antibiotic antivirals. However, Phage Display-derived MAbs have an overall success rate of 35% of passage from clinical phase I to launch, compared to an average of 12% for a small-molecule drug candidate [59]. In this regard, Phage Display-derived MAb is considered an important alternative approach to infectious disease treatment compared to classical small-molecule discovery. Raxibacumab is an example of a fast-track designation from the FDA, providing the expedition of the drug to use against B. anthracis infection. This bacterium secretes proteins, the lethal factor and the edema factor, that inhibit normal immune system functioning that ultimately cause cell death. The entry of these factors is mediated by the protective antigen (PA), also secreted by the bacteria. Raxibacumab is directed to B. anthracis PA and thus prevents the cellular uptake of the lethal factor and edema factor. The MAb was developed by the Phage Display, using a library licensed by Human Genome Sciences (HGS), which now is GlaxoSmithKline (GSK), from Cambridge Antibody Technology. Recombinant PA was used in the biopanning process to select candidates, which were then screened in assays for PA neutralization [60, 61].
\nThe Phage Display technology provides a rapid methodology for building a high-affinity antibody library from immune repertoires. These antibodies can be used to generate diagnostic bases or be tested for therapeutic capability. For example, from the repertoire of B cells of patients who recovered from influenza virus infections or who received vaccination, it was possible to isolate, by Phage Display, several antibodies with the neutralization property of different influenza virus subtypes. Another example of antibody-based immunotherapy developed by Phage Display involves the identification of antibodies specific to different types of coronavirus. These studies are an example of how Phage Display enables the selection of antibodies by an in vitro process, especially for new or mutated pathogens in an outbreak of emergent infectious diseases, as it uses only pathogen-specific antigens [39, 62, 63].
\nParticularly, MAbs play an important role in antiviral immunity preventing viral replication and disease progress. Antibodies can interfere with virus infection by various mechanisms. The primary mechanism is by targeting the virus surface proteins; antibodies can inhibit virus attachment to cell surface receptors. Another main mechanism is targeting non-receptor-binding regions, such as in endosomal membrane fusion step where neutralization can occur by interfering virus conformational changes. In general, flavivirus particles tend to display on their surface continuum epitopes that induce potently neutralizing antibodies, blocking viral entry into cells [58].
\nFrom the understanding of the structure of each flavivirus, it was possible to determine the antibody targets most conducive to the diagnosis and protection of the disease [64]. It is important to note that flaviviruses are not static particles and viral proteins are in a constant dynamic movement, a process known as breathing, in order to transiently reveal new epitopes, and this characteristic influences the detection and neutralization capabilities of antibodies [10].
\nSo far, no MAbs against flavivirus have reached the clinical stages, except for WNV. However, several studies have demonstrated potentially neutralizing MAbs that could be therapeutically used against these infections [65, 66]. Different antibodies have been generated exploring the characteristics of viral epitopes. The E glycoprotein is the main target of neutralizing antibodies, especially the E DIII has been described to be the most efficient to block adsorption of DENV in vitro [58]. In the field of DENV diagnosis, MAbs have been especially applied to distinguish DENV serotypes [67, 68]. For this purpose E and soluble NS1 proteins are the main targets of these MAbs using different assay formats, such as ELISA and rapid test based on immunochromatography [69].
\nThe pre-existing cross-reactive antibodies can be boosted in a secondary infection with antigenically related molecules; consequently antibody to fusion loop tends to have dominance upon sequential infections with DENV or other flaviviruses. Antibodies to E-dimer epitope (EDE) are divided into two subclasses, EDE1 and EDE2, based on the recognition of the conserved glycan Asn-153 of DENV [58]. EDE1 has already been shown to potently neutralize ZIKV infection; this class of antibody does not require glycosylation for binding [70]. However, EDE2 have a reduced neutralization potential against ZIKV, once these antibodies have a strongly binding dependence on the glycan, which have different positioning between ZIKV and DENV [66].
\nThe generation of monoclonal antibodies by Phage Display can help improve the speed at which new antibodies are produced. The freedom associated with recombinant antibodies also allows them to be customized for various applications, allowing the development of MAbs with binding, functional, and pharmacological characteristics suitable for a therapeutic and diagnostic use [37]. Thus, the use of Phage Display to identify antibodies against DENV, as well as for other flavivirus, can contribute to the knowledge of the specific antigenic properties of the virus, allowing to generate new perspectives for the development of efficient therapies, vaccines, and diagnostic platforms of this virus.
\nTo obtain specific antibodies to the DENV, it is possible to employ different libraries of Phage Display and distinct selection approaches depending on the purpose. Using a llama immune library, a diagnostic methodology was developed based on antibodies capable of binding to the NS1 of the four DENV serotypes, without cross-reacting with NS1 of other flaviviruses. The panning was performed with immobilized antigen, so that in each round, the phage population was incubated with NS1 from one of the serotypes, resulting in phage specific to all forms of NS1. To characterize the diagnostic potential of the antibodies, MAbs were addressed [71]. Lebani et al. [72] isolate four serotype-specific human antibodies through a negative selection strategy. Each MAb was specific for NS1 from a DENV serotype, without cross-linking.
\nIn another approach, Cabezas et al. [73] worked with human naïve library to obtain a panel of antibody fragments with different specificity toward DENV serotypes. The biopanning was made against inactivated DENV-containing supernatants harvested from infected Vero cells for 4 days with each serotype. These supernatants were directly used for Phage Display biopanning. A panel of nine scFvs, where seven were specific for DENV2, DENV3, and DENV4 while the other two were cross-reactive, was obtained. Silva [74] employed a subtractive biopanning, in which a human Fab Phage Display library was first incubated against ZIKV particles, to eliminate the majority of antibodies that binds to this viral particle, and nonbinding phages were then incubated against DENV2 particles, followed by elution of ligand phages. Analysis by NGS of the pool of phages retrieved after four rounds of this biopanning showed that the VH and VL sequences obtained may not have cross-reactivity between DENV2 and ZIKV.
\nAntibody-based DENV infection therapies developed by Phage Display have also been reported. Saokaew et al. [75] show that a human scFv specific for DIII was able to neutralize DENV2 infection at in vitro assays. The human MAb 5A, originated from a selection of Phage Display, has been shown to be specific to the fusion loop, both in its pre-fusion conformation to the endocytic membrane, before infection, and in its acid-dependent post-fusion conformation, during the final viral infection process, and proved to be a potent neutralizing antibody of different strains of yellow fever virus in vitro and in vivo. Thus, MAb 5A prevents both virus attachment and fusion. As the fusion loop is a highly conserved antigen, there is a high possibility that 5A neutralizes other flaviviruses [76]. In the same way, Wu et al. [77] identified a panel of human MAbs that target DIII of the ZIKV envelope protein from a large Phage Display naïve antibody library. These germline-like antibodies bound ZIKV DIII specifically with high affinities. These MAbs neutralized the currently circulating ZIKV strains and showed a synergistic effect in neutralizing ZIKV in vitro and in a mouse model of ZIKV infection.
\nAs an example of Phage Display using immune libraries to select high-affinity MAbs, Mwale et al. [78] analyzed the immune response in chicken through the determination of the polyclonal immunoglobulin yolk (IgY) against a truncated Zika virus envelope protein. They induced an immune response in white leghorn laying hens against the ZIKV envelope protein. A high-level titer of anti-ZIKV envelope protein antibodies was detected and after constructed two antibody libraries; they found some scFvs that showed specific binding activities toward the ZIKV envelope protein.
\nMoreover, Phage Display has been used to find therapeutic antibody fragments against nonstructural proteins. A MAb fragment Fab NS3-specific obtained from a naïve human Fab Phage Display library was shown to inhibit the ATPase and helicase activities of NS3 protein and reduces DENV replication in vitro. The ability to inhibit in vitro DENV replication may be exploited in a therapeutic approach [79]. Using a human scFv Phage Display library, Poungpair et al. [80] obtained two scFv clones that bound specifically to the NS1 of DENV 2, used as antigen in phage biopanning. They observed that cells infected with DENV2 and treated with selected scFvs had significant reduction of the infectious viral particles in supernatant. Besides that, the analysis of mimotope/epitope mapping indicated that the NS1 sites bound by antibody fragments can lead to interference of the virus replication by affecting the virus release.
\nOver the years many discoveries have been made aiming for the control and treatment of emerging infectious diseases, some of those include the development of efficient drugs that could act specifically in the pathogen to eliminate efficiently. In this way, MAbs emerged as the main biological drugs for this purpose. Moreover, MAbs play an important role in the development of serological diagnostic test that could be used for tracking the spread of disease and determining public health prevention measures and clinical care. There are still great questions around the infection mechanisms by flavivirus, especially related to the cross-reactivity between them and the risk of complications. In this way, the use of effective, fast, and robust approaches to facilitate the development of flavivirus MAbs is a determinant factor.
\nThe Phage Display technology presents a great potential to provide optimized strategies, allowing the obtention of high-affinity human antibodies for a specific target. Some of the main advantages that make this technology so promising are the possibility to obtain human MAbs without in vivo immunization; the enormous diversity of variant antibodies displayed within a single library; the ability to tailor MAbs with the desired properties by using different strategies such as depletion, guided selection, and biochemical control; and the possibility to be applied against practically any kind of target antigen [33]. However, some concerns about Phage Display are the dependence of the initial library quality, the difficulties in the post-selection step involving analysis and recombinant antibody production, and the possibility of obtention of low-affinity antibodies, especially in naïve libraries [35]. Considering the impact of infectious diseases on the health system and economy, mainly DENV and ZIKV, that co-circulate in tropical countries, MAbs obtained by Phage Display may overcome issues related to versatility and high throughputness compared to other approaches, playing a larger role in the actual and future public health response.
\nThe authors would like to thank the Immunology Department of Adolfo Lutz Institute, the Coordination of Improvement of Postgraduate Level Personnel (CAPES), and the National Council for Scientific and Technological Development (CNPq). The authors also thank the Cellular Biology Department from the University of Brazilia, Post-Graduate Program in Molecular Biology (UNB), and Foundation for Scientific and Technological Enterprises (FINATEC) for the financial and technical support. This study was financed under grant CNPq/CAPES/MS-DECIT No. 440812/2016-0 and FINEP under sgrant No. 01.16.0075, under the coordination of Dr. Carlos R. Prudencio.
\nThe authors declare no conflict of interest.
Our books are published online and are accessible for free. However, if you are interested in ordering your hardcover copy, you can do so by contacting our Print Sales Department at orders@intechopen.com. All IntechOpen books are printed on demand in full-colour and delivered in signature packaging through free DHL Express delivery. A selection of our books in soft cover is also available through Amazon.
',metaTitle:"Order Print Copies",metaDescription:"Our books are published online and are accessible for free. However, if you are interested in ordering your printed copy, you can do so by contacting our Print Sales Department at orders@intechopen.com.\n\nOur hardcover books are carefully designed and printed on wood-free premium quality paper.\n\nThe paper size is 155 mm x 225 mm (6.1 X 8.8 inches).",metaKeywords:null,canonicalURL:"/page/order-print-copies",contentRaw:'[{"type":"htmlEditorComponent","content":"InTechOpen contributors can order print books at a special price ranging from:
\\n\\nFor a quote please contact us directly at orders@intechopen.com The quote will be sent to you within 1-2 business days.
\\n\\nAll of the books and chapters can be browsed online. To obtain InTechOpen's full book catalogue in PDF, please contact us.
\\n\\n\\n\\nIntechOpen works with award winning print-houses and we hold to the fact that all of our printed products are of the highest quality.
\\n\\nPrint copies of our publications are most often purchased as individual purchases by universities, libraries, institutions and academia personnel, hence increasing the visibility and outreach of our authors' published work among science communities and institutions. Our books are available at our direct Print Sales Department and through selected representatives throughout the world.
\\n\\nIndia - CBS Publishers & Distributors Pvt. Ltd.
\\n\\nASEAN - Books International
\\n\\nChina Publishers Services Ltd - CPS
\\n\\nMallory International Ltd
\\n\\nFor partnership opportunities, please contact orders@intechopen.com.
\\n\\n*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add a Book Value-Added Tax of 5%. Institutions and companies registered as VAT taxable entities in their own EU member state, will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'InTechOpen contributors can order print books at a special price ranging from:
\n\nFor a quote please contact us directly at orders@intechopen.com The quote will be sent to you within 1-2 business days.
\n\nAll of the books and chapters can be browsed online. To obtain InTechOpen's full book catalogue in PDF, please contact us.
\n\n\n\nIntechOpen works with award winning print-houses and we hold to the fact that all of our printed products are of the highest quality.
\n\nPrint copies of our publications are most often purchased as individual purchases by universities, libraries, institutions and academia personnel, hence increasing the visibility and outreach of our authors' published work among science communities and institutions. Our books are available at our direct Print Sales Department and through selected representatives throughout the world.
\n\nIndia - CBS Publishers & Distributors Pvt. Ltd.
\n\nASEAN - Books International
\n\nChina Publishers Services Ltd - CPS
\n\nMallory International Ltd
\n\nFor partnership opportunities, please contact orders@intechopen.com.
\n\n*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add a Book Value-Added Tax of 5%. Institutions and companies registered as VAT taxable entities in their own EU member state, will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:117096},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateEndThirdStepPublish",topicId:"10"},books:[{type:"book",id:"10761",title:"Glaciology",subtitle:null,isOpenForSubmission:!0,hash:"bd112c839a9b8037f1302ca6c0d55a2a",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10761.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10762",title:"Cosmology",subtitle:null,isOpenForSubmission:!0,hash:"f28a2213571fb878839bcbacb9827a1d",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10762.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10756",title:"Urban Agglomeration",subtitle:null,isOpenForSubmission:!0,hash:"732ee82bf579a4bc4c5c929ceba2db26",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10756.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8485",title:"Weather Forecasting",subtitle:null,isOpenForSubmission:!0,hash:"eadbd6f9c26be844062ce5cd3b3eb573",slug:null,bookSignature:"Associate Prof. Muhammad Saifullah",coverURL:"https://cdn.intechopen.com/books/images_new/8485.jpg",editedByType:null,editors:[{id:"320968",title:"Associate Prof.",name:"Muhammad",surname:"Saifullah",slug:"muhammad-saifullah",fullName:"Muhammad Saifullah"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10404",title:"Evapotranspiration - Recent Advances and Applications",subtitle:null,isOpenForSubmission:!0,hash:"babca2dea1c80719111734cc57a21a4c",slug:null,bookSignature:"Dr. Amin Talei",coverURL:"https://cdn.intechopen.com/books/images_new/10404.jpg",editedByType:null,editors:[{id:"335732",title:"Dr.",name:"Amin",surname:"Talei",slug:"amin-talei",fullName:"Amin Talei"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7724",title:"Climate Issues in Asia and Africa - Examining Climate, Its Flux, the Consequences, and Society's Responses",subtitle:null,isOpenForSubmission:!0,hash:"c1bd1a5a4dba07b95a5ae5ef0ecf9f74",slug:null,bookSignature:" John P. Tiefenbacher",coverURL:"https://cdn.intechopen.com/books/images_new/7724.jpg",editedByType:null,editors:[{id:"73876",title:"Dr.",name:"John P.",surname:"Tiefenbacher",slug:"john-p.-tiefenbacher",fullName:"John P. Tiefenbacher"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10556",title:"Petrology",subtitle:null,isOpenForSubmission:!0,hash:"be71a270b1196a96cdc1162f64f9a966",slug:null,bookSignature:"Prof. Ali Ismail Al-Juboury",coverURL:"https://cdn.intechopen.com/books/images_new/10556.jpg",editedByType:null,editors:[{id:"58570",title:"Prof.",name:"Ali",surname:"Al-Juboury",slug:"ali-al-juboury",fullName:"Ali Al-Juboury"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10210",title:"Solar Planets and Exoplanets",subtitle:null,isOpenForSubmission:!0,hash:"b7f57c0e93406f0925482b204ad392ec",slug:null,bookSignature:"Dr. Joseph John Bevelacqua",coverURL:"https://cdn.intechopen.com/books/images_new/10210.jpg",editedByType:null,editors:[{id:"115462",title:"Dr.",name:"Joseph",surname:"Bevelacqua",slug:"joseph-bevelacqua",fullName:"Joseph Bevelacqua"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10850",title:"Extreme Weather",subtitle:null,isOpenForSubmission:!0,hash:"a5cc0122cbb90c28905e22dc439e6e14",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10850.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10851",title:"Volcanology",subtitle:null,isOpenForSubmission:!0,hash:"e25288216b83d0a2459f77c612ead09f",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10851.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10849",title:"Earthquake Forecasting",subtitle:null,isOpenForSubmission:!0,hash:"2a5ddc8f109bb194466cff2367c26400",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10849.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10952",title:"Soil Science",subtitle:null,isOpenForSubmission:!0,hash:"0aa879d595f22de7f134b32189042eb0",slug:null,bookSignature:"",coverURL:"//cdnintech.com/web/frontend/www/assets/cover.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:18},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:14},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:63},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:12},popularBooks:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Health",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-health",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"966",title:"Dynamical Systems Theory",slug:"dynamical-systems-theory",parent:{title:"Applied Mathematics",slug:"applied-mathematics"},numberOfBooks:9,numberOfAuthorsAndEditors:177,numberOfWosCitations:50,numberOfCrossrefCitations:59,numberOfDimensionsCitations:109,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"dynamical-systems-theory",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7662",title:"Nonlinear Systems",subtitle:"Theoretical Aspects and Recent Applications",isOpenForSubmission:!1,hash:"fdcb3bf6de1d84506ffc6aa9e5b691b3",slug:"nonlinear-systems-theoretical-aspects-and-recent-applications",bookSignature:"Walter Legnani and Terry E. Moschandreou",coverURL:"https://cdn.intechopen.com/books/images_new/7662.jpg",editedByType:"Edited by",editors:[{id:"199059",title:"Dr.",name:"Walter",middleName:"Edgardo",surname:"Legnani",slug:"walter-legnani",fullName:"Walter Legnani"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9324",title:"Dynamical Systems Theory",subtitle:null,isOpenForSubmission:!1,hash:"413cbcf9c048bb251eca1b5e32bbc640",slug:"dynamical-systems-theory",bookSignature:"Jan Awrejcewicz and Dariusz Grzelczyk",coverURL:"https://cdn.intechopen.com/books/images_new/9324.jpg",editedByType:"Edited by",editors:[{id:"68338",title:"Prof.",name:"Jan",middleName:null,surname:"Awrejcewicz",slug:"jan-awrejcewicz",fullName:"Jan Awrejcewicz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7776",title:"Research Advances in Chaos Theory",subtitle:null,isOpenForSubmission:!1,hash:"e9646ec4b2bff873ce958ed4d5ad7248",slug:"research-advances-in-chaos-theory",bookSignature:"Paul Bracken",coverURL:"https://cdn.intechopen.com/books/images_new/7776.jpg",editedByType:"Edited by",editors:[{id:"92883",title:"Prof.",name:"Paul",middleName:null,surname:"Bracken",slug:"paul-bracken",fullName:"Paul Bracken"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7293",title:"Fractal Analysis",subtitle:null,isOpenForSubmission:!1,hash:"136b50bd77fedb29057889faaca37947",slug:"fractal-analysis",bookSignature:"Sid-Ali Ouadfeul",coverURL:"https://cdn.intechopen.com/books/images_new/7293.jpg",editedByType:"Edited by",editors:[{id:"103826",title:"Dr.",name:"Sid-Ali",middleName:null,surname:"Ouadfeul",slug:"sid-ali-ouadfeul",fullName:"Sid-Ali Ouadfeul"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6651",title:"Nonlinear Systems",subtitle:"Modeling, Estimation, and Stability",isOpenForSubmission:!1,hash:"085cfe19a4bd48a9e8034b2e5cc17172",slug:"nonlinear-systems-modeling-estimation-and-stability",bookSignature:"Mahmut Reyhanoglu",coverURL:"https://cdn.intechopen.com/books/images_new/6651.jpg",editedByType:"Edited by",editors:[{id:"15068",title:"Dr.",name:"Mahmut",middleName:null,surname:"Reyhanoglu",slug:"mahmut-reyhanoglu",fullName:"Mahmut Reyhanoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6216",title:"Complexity in Biological and Physical Systems",subtitle:"Bifurcations, Solitons and Fractals",isOpenForSubmission:!1,hash:"c511a26efc1b9c0638c8f9244240cb93",slug:"complexity-in-biological-and-physical-systems-bifurcations-solitons-and-fractals",bookSignature:"Ricardo López-Ruiz",coverURL:"https://cdn.intechopen.com/books/images_new/6216.jpg",editedByType:"Edited by",editors:[{id:"9849",title:"Prof.",name:"Ricardo",middleName:null,surname:"Lopez-Ruiz",slug:"ricardo-lopez-ruiz",fullName:"Ricardo Lopez-Ruiz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5804",title:"Fractal Analysis",subtitle:"Applications in Physics, Engineering and Technology",isOpenForSubmission:!1,hash:"a3d42b4b44ba9d7d72f0e91442da7b4b",slug:"fractal-analysis-applications-in-physics-engineering-and-technology",bookSignature:"Fernando Brambila",coverURL:"https://cdn.intechopen.com/books/images_new/5804.jpg",editedByType:"Edited by",editors:[{id:"60921",title:"Dr.",name:"Fernando",middleName:null,surname:"Brambila",slug:"fernando-brambila",fullName:"Fernando Brambila"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5513",title:"Dynamical Systems",subtitle:"Analytical and Computational Techniques",isOpenForSubmission:!1,hash:"9ba4129f30ef1b92fd4b7ae193781183",slug:"dynamical-systems-analytical-and-computational-techniques",bookSignature:"Mahmut Reyhanoglu",coverURL:"https://cdn.intechopen.com/books/images_new/5513.jpg",editedByType:"Edited by",editors:[{id:"15068",title:"Dr.",name:"Mahmut",middleName:null,surname:"Reyhanoglu",slug:"mahmut-reyhanoglu",fullName:"Mahmut Reyhanoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2508",title:"Nonlinearity, Bifurcation and Chaos",subtitle:"Theory and Applications",isOpenForSubmission:!1,hash:"cce4e2af0e23321e7072373518985b63",slug:"nonlinearity-bifurcation-and-chaos-theory-and-applications",bookSignature:"Jan Awrejcewicz and Peter Hagedorn",coverURL:"https://cdn.intechopen.com/books/images_new/2508.jpg",editedByType:"Edited by",editors:[{id:"68338",title:"Prof.",name:"Jan",middleName:null,surname:"Awrejcewicz",slug:"jan-awrejcewicz",fullName:"Jan Awrejcewicz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:9,mostCitedChapters:[{id:"40430",doi:"10.5772/50403",title:"Mathematical Modelling and Numerical Investigations on the Coanda Effect",slug:"mathematical-modelling-and-numerical-investigations-on-the-coanda-effect",totalDownloads:4575,totalCrossrefCites:12,totalDimensionsCites:18,book:{slug:"nonlinearity-bifurcation-and-chaos-theory-and-applications",title:"Nonlinearity, Bifurcation and Chaos",fullTitle:"Nonlinearity, Bifurcation and Chaos - Theory and Applications"},signatures:"A. Dumitrache, F. Frunzulica and T.C. Ionescu",authors:[{id:"151443",title:"Dr.",name:"Dumitrache",middleName:null,surname:"Alexandru",slug:"dumitrache-alexandru",fullName:"Dumitrache Alexandru"},{id:"151449",title:"Dr.",name:"Frunzulica",middleName:null,surname:"Florin",slug:"frunzulica-florin",fullName:"Frunzulica Florin"},{id:"151451",title:"Dr.",name:"Ionescu",middleName:null,surname:"Tudor",slug:"ionescu-tudor",fullName:"Ionescu Tudor"}]},{id:"53920",doi:"10.5772/67216",title:"Integral-Equation Formulations of Plasmonic Problems in the Visible Spectrum and Beyond",slug:"integral-equation-formulations-of-plasmonic-problems-in-the-visible-spectrum-and-beyond",totalDownloads:1252,totalCrossrefCites:9,totalDimensionsCites:11,book:{slug:"dynamical-systems-analytical-and-computational-techniques",title:"Dynamical Systems",fullTitle:"Dynamical Systems - Analytical and Computational Techniques"},signatures:"Abdulkerim Çekinmez, Barişcan Karaosmanoğlu and Özgür Ergül",authors:[{id:"195936",title:"Associate Prof.",name:"Ozgur",middleName:null,surname:"Ergul",slug:"ozgur-ergul",fullName:"Ozgur Ergul"},{id:"203161",title:"Mr.",name:"Abdulkerim",middleName:null,surname:"Cekinmez",slug:"abdulkerim-cekinmez",fullName:"Abdulkerim Cekinmez"},{id:"203162",title:"MSc.",name:"Bariscan",middleName:null,surname:"Karaosmanoglu",slug:"bariscan-karaosmanoglu",fullName:"Bariscan Karaosmanoglu"}]},{id:"40437",doi:"10.5772/48811",title:"FSM Scenarios of Laminar-Turbulent Transition in Incompressible Fluids",slug:"fsm-scenarios-of-laminar-turbulent-transition-in-incompressible-fluids",totalDownloads:1378,totalCrossrefCites:4,totalDimensionsCites:7,book:{slug:"nonlinearity-bifurcation-and-chaos-theory-and-applications",title:"Nonlinearity, Bifurcation and Chaos",fullTitle:"Nonlinearity, Bifurcation and Chaos - Theory and Applications"},signatures:"N.M. Evstigneev and N.A. Magnitskii",authors:[{id:"96107",title:"Prof.",name:"Nikolai A.",middleName:"Alexandrovich",surname:"Magnitskii",slug:"nikolai-a.-magnitskii",fullName:"Nikolai A. Magnitskii"},{id:"151627",title:"Dr.",name:"N. M.",middleName:null,surname:"Evstigneev",slug:"n.-m.-evstigneev",fullName:"N. M. Evstigneev"}]}],mostDownloadedChaptersLast30Days:[{id:"54366",title:"Solution of Differential Equations with Applications to Engineering Problems",slug:"solution-of-differential-equations-with-applications-to-engineering-problems",totalDownloads:5239,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"dynamical-systems-analytical-and-computational-techniques",title:"Dynamical Systems",fullTitle:"Dynamical Systems - Analytical and Computational Techniques"},signatures:"Cheng Yung Ming",authors:[{id:"191017",title:"Dr.",name:"Cheng",middleName:null,surname:"Y.M.",slug:"cheng-y.m.",fullName:"Cheng Y.M."}]},{id:"64463",title:"Fractal Analysis of Time-Series Data Sets: Methods and Challenges",slug:"fractal-analysis-of-time-series-data-sets-methods-and-challenges",totalDownloads:1684,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"fractal-analysis",title:"Fractal Analysis",fullTitle:"Fractal Analysis"},signatures:"Ian Pilgrim and Richard P. Taylor",authors:[{id:"262574",title:"Ph.D.",name:"Ian",middleName:null,surname:"Pilgrim",slug:"ian-pilgrim",fullName:"Ian Pilgrim"},{id:"262816",title:"Prof.",name:"Richard",middleName:null,surname:"Taylor",slug:"richard-taylor",fullName:"Richard Taylor"}]},{id:"71158",title:"A Shamanskii-Like Accelerated Scheme for Nonlinear Systems of Equations",slug:"a-shamanskii-like-accelerated-scheme-for-nonlinear-systems-of-equations",totalDownloads:209,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"nonlinear-systems-theoretical-aspects-and-recent-applications",title:"Nonlinear Systems",fullTitle:"Nonlinear Systems -Theoretical Aspects and Recent Applications"},signatures:"Ibrahim Mohammed Sulaiman, Mustafa Mamat and Umar Audu Omesa",authors:[{id:"299084",title:"Dr.",name:"Mustafa",middleName:null,surname:"Mamat",slug:"mustafa-mamat",fullName:"Mustafa Mamat"},{id:"316957",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Sulaiman",slug:"ibrahim-sulaiman",fullName:"Ibrahim Sulaiman"}]},{id:"67141",title:"A Review on Fractional Differential Equations and a Numerical Method to Solve Some Boundary Value Problems",slug:"a-review-on-fractional-differential-equations-and-a-numerical-method-to-solve-some-boundary-value-pr",totalDownloads:1011,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"nonlinear-systems-theoretical-aspects-and-recent-applications",title:"Nonlinear Systems",fullTitle:"Nonlinear Systems -Theoretical Aspects and Recent Applications"},signatures:"María I. Troparevsky, Silvia A. Seminara and Marcela A. Fabio",authors:[{id:"296689",title:"Dr.",name:"Maria Ines",middleName:null,surname:"Troparevsky",slug:"maria-ines-troparevsky",fullName:"Maria Ines Troparevsky"},{id:"296690",title:"Prof.",name:"Silvia Alejandra",middleName:null,surname:"Seminara",slug:"silvia-alejandra-seminara",fullName:"Silvia Alejandra Seminara"},{id:"296691",title:"Prof.",name:"Marcela Antonieta",middleName:null,surname:"Fabio",slug:"marcela-antonieta-fabio",fullName:"Marcela Antonieta Fabio"}]},{id:"57485",title:"Small-Angle Scattering from Mass and Surface Fractals",slug:"small-angle-scattering-from-mass-and-surface-fractals",totalDownloads:738,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"complexity-in-biological-and-physical-systems-bifurcations-solitons-and-fractals",title:"Complexity in Biological and Physical Systems",fullTitle:"Complexity in Biological and Physical Systems - Bifurcations, Solitons and Fractals"},signatures:"Eugen Mircea Anitas",authors:[{id:"213626",title:"Dr.",name:"Eugen",middleName:null,surname:"Anitas",slug:"eugen-anitas",fullName:"Eugen Anitas"}]},{id:"54086",title:"Generalized Ratio Control of Discrete-Time Systems",slug:"generalized-ratio-control-of-discrete-time-systems",totalDownloads:1077,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"dynamical-systems-analytical-and-computational-techniques",title:"Dynamical Systems",fullTitle:"Dynamical Systems - Analytical and Computational Techniques"},signatures:"Dušan Krokavec and Anna Filasová",authors:[{id:"18818",title:"Prof.",name:"Dušan",middleName:null,surname:"Krokavec",slug:"dusan-krokavec",fullName:"Dušan Krokavec"},{id:"22287",title:"Prof.",name:"Anna",middleName:null,surname:"Filasová",slug:"anna-filasova",fullName:"Anna Filasová"}]},{id:"55048",title:"Application of Fractal Dimension in Industry Practice",slug:"application-of-fractal-dimension-in-industry-practice",totalDownloads:1148,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"fractal-analysis-applications-in-physics-engineering-and-technology",title:"Fractal Analysis",fullTitle:"Fractal Analysis - Applications in Physics, Engineering and Technology"},signatures:"Vlastimil Hotař",authors:[{id:"199387",title:"Ph.D.",name:"Vlastimil",middleName:null,surname:"Hotař",slug:"vlastimil-hotar",fullName:"Vlastimil Hotař"}]},{id:"54621",title:"Specific Emitter Identification Based on Fractal Features",slug:"specific-emitter-identification-based-on-fractal-features",totalDownloads:1593,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"fractal-analysis-applications-in-physics-engineering-and-technology",title:"Fractal Analysis",fullTitle:"Fractal Analysis - Applications in Physics, Engineering and Technology"},signatures:"Janusz Dudczyk",authors:[{id:"197688",title:"Prof.",name:"Janusz",middleName:null,surname:"Dudczyk",slug:"janusz-dudczyk",fullName:"Janusz Dudczyk"}]},{id:"58685",title:"Mechanical Models of Microtubules",slug:"mechanical-models-of-microtubules",totalDownloads:522,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"complexity-in-biological-and-physical-systems-bifurcations-solitons-and-fractals",title:"Complexity in Biological and Physical Systems",fullTitle:"Complexity in Biological and Physical Systems - Bifurcations, Solitons and Fractals"},signatures:"Slobodan Zdravković",authors:[{id:"210601",title:"Dr.",name:"Slobodan",middleName:null,surname:"Zdravkovic",slug:"slobodan-zdravkovic",fullName:"Slobodan Zdravkovic"}]},{id:"54338",title:"Emergence of Classical Distributions from Quantum Distributions: The Continuous Energy Spectra Case",slug:"emergence-of-classical-distributions-from-quantum-distributions-the-continuous-energy-spectra-case",totalDownloads:1066,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"dynamical-systems-analytical-and-computational-techniques",title:"Dynamical Systems",fullTitle:"Dynamical Systems - Analytical and Computational Techniques"},signatures:"Gabino Torres-Vega",authors:[{id:"93519",title:"Dr.",name:"Gabino",middleName:null,surname:"Torres-Vega",slug:"gabino-torres-vega",fullName:"Gabino Torres-Vega"}]}],onlineFirstChaptersFilter:{topicSlug:"dynamical-systems-theory",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/135454/mitsuru-arima",hash:"",query:{},params:{id:"135454",slug:"mitsuru-arima"},fullPath:"/profiles/135454/mitsuru-arima",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()