\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-partners-with-ehs-for-digital-advertising-representation-20210416",title:"IntechOpen Partners with EHS for Digital Advertising Representation"},{slug:"intechopen-signs-new-contract-with-cepiec-china-for-distribution-of-open-access-books-20210319",title:"IntechOpen Signs New Contract with CEPIEC, China for Distribution of Open Access Books"},{slug:"150-million-downloads-and-counting-20210316",title:"150 Million Downloads and Counting"},{slug:"intechopen-secures-indefinite-content-preservation-with-clockss-20210309",title:"IntechOpen Secures Indefinite Content Preservation with CLOCKSS"},{slug:"intechopen-expands-to-all-global-amazon-channels-with-full-catalog-of-books-20210308",title:"IntechOpen Expands to All Global Amazon Channels with Full Catalog of Books"},{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"}]},book:{item:{type:"book",id:"9731",leadTitle:null,fullTitle:"Oxidoreductase",title:"Oxidoreductase",subtitle:null,reviewType:"peer-reviewed",abstract:"Oxidoreductase enzymes are a group of enzymes that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. Oxidoreductase enzymes utilize NADP+ or NAD+ as cofactors. Oxidoreductase enzymes include the following: oxidase, dehydrogenase, peroxidase, hydroxylase, oxygenase, and reductase. Most oxidoreductase enzymes are dehydrogenases. However, reductases are also common. The accepted nomenclature for dehydrogenases is “donor dehydrogenase”, where the donor is the oxidized substrate. Metabolic abnormalities disorders resulting from a deficiency (quantitative and qualitative) or from over-activity of oxidoreductase, which may contribute to the decreased normal performance of life, are becoming common. This book covers the potential applications of oxidoreductases on the growth of oxidoreductase-based diagnostic tests and better biosensors in the design of inventive systems for crucial co-enzyme generations and in the synthesis of polymers and organic substrates. The book describes the role of oxidoreductase as essential in medical drug formation. It can be employed to produce a huge amount of compounds that act as medical mediators like Cephalosporin (beta lactam antibiotic). Furthermore, the idea of how to use different enzymes as targets for medical treatment in different types of cancers is also described in this book.",isbn:"978-1-83880-901-0",printIsbn:"978-1-83880-900-3",pdfIsbn:"978-1-83880-902-7",doi:"10.5772/intechopen.87536",price:119,priceEur:129,priceUsd:155,slug:"oxidoreductase",numberOfPages:180,isOpenForSubmission:!1,isInWos:null,hash:"852e6f862c85fc3adecdbaf822e64e6e",bookSignature:"Mahmoud Ahmed Mansour",publishedDate:"February 17th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",numberOfDownloads:1017,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfDimensionsCitations:1,hasAltmetrics:0,numberOfTotalCitations:2,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 14th 2020",dateEndSecondStepPublish:"September 10th 2020",dateEndThirdStepPublish:"November 9th 2020",dateEndFourthStepPublish:"January 28th 2021",dateEndFifthStepPublish:"March 29th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour",profilePictureURL:"https://mts.intechopen.com/storage/users/224662/images/system/224662.jpg",biography:"Mahmoud Mansour Ph.D. is a professor of Biochemistry at the Pharmaceutical Sciences Department, College of Pharmacy King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. His specialization includes molecular biology, biochemical pharmacology, pharmacogenetics, and biochemistry. His research fields are biochemical pharmacological studies in cancers (especially hepatic cancer), antioxidants, oxidative stress, proteasome (and its role in the treatment of hepatic cancer), experimental gastroenterology, clinical gastroenterology, and diabetes. He has published more than 60 papers in peer-reviewed journals. He received the State Encouragement award from the Scientific Research Academy, (1998). Fourteen of his students were appointed as full university professors in Egypt and Saudi Arabia.",institutionString:"King Saud bin Abdulaziz University for Health Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"King Saud bin Abdulaziz University for Health Sciences",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"50",title:"Enzymology",slug:"biochemistry-genetics-and-molecular-biology-enzymology"}],chapters:[{id:"73110",title:"Biological Application and Disease of Oxidoreductase Enzymes",doi:"10.5772/intechopen.93328",slug:"biological-application-and-disease-of-oxidoreductase-enzymes",totalDownloads:165,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Mezgebu Legesse Habte and Etsegenet Assefa Beyene",downloadPdfUrl:"/chapter/pdf-download/73110",previewPdfUrl:"/chapter/pdf-preview/73110",authors:[{id:"321940",title:"M.Sc.",name:"Mezgebu Legesse",surname:"Habte",slug:"mezgebu-legesse-habte",fullName:"Mezgebu Legesse Habte"},{id:"322372",title:"MSc.",name:"Etsegenet Assefa",surname:"Beyene",slug:"etsegenet-assefa-beyene",fullName:"Etsegenet Assefa Beyene"}],corrections:null},{id:"73831",title:"Applications of Oxidoreductases",doi:"10.5772/intechopen.94409",slug:"applications-of-oxidoreductases",totalDownloads:143,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Sandhya Rani Gogoi",downloadPdfUrl:"/chapter/pdf-download/73831",previewPdfUrl:"/chapter/pdf-preview/73831",authors:[{id:"322572",title:"Ph.D.",name:"Sandhya Rani",surname:"Gogoi",slug:"sandhya-rani-gogoi",fullName:"Sandhya Rani Gogoi"}],corrections:null},{id:"73142",title:"Role of Subcellular ROS in Providing Resilience to Vascular Endothelium",doi:"10.5772/intechopen.93568",slug:"role-of-subcellular-ros-in-providing-resilience-to-vascular-endothelium",totalDownloads:133,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Sarah R. Aldosari, Maan A. Awad, Frank W. Sellke and Md. Ruhul Abid",downloadPdfUrl:"/chapter/pdf-download/73142",previewPdfUrl:"/chapter/pdf-preview/73142",authors:[{id:"164682",title:"Prof.",name:"Frank W.",surname:"Sellke",slug:"frank-w.-sellke",fullName:"Frank W. Sellke"},{id:"178147",title:"Dr.",name:"Md. Ruhul",surname:"Abid",slug:"md.-ruhul-abid",fullName:"Md. Ruhul Abid"},{id:"328673",title:"Mr.",name:"Maan A.",surname:"Awad",slug:"maan-a.-awad",fullName:"Maan A. Awad"},{id:"328674",title:"Ms.",name:"Sarah R.",surname:"Aldosari",slug:"sarah-r.-aldosari",fullName:"Sarah R. Aldosari"}],corrections:null},{id:"73434",title:"The Impact of Oxidoreductases-Related MicroRNAs in Glucose Metabolism of Renal Cell Carcinoma and Prostate Cancer",doi:"10.5772/intechopen.93932",slug:"the-impact-of-oxidoreductases-related-micrornas-in-glucose-metabolism-of-renal-cell-carcinoma-and-pr",totalDownloads:86,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Mariana Gomes Morais, Francisca Guilherme Carvalho Dias, João Alexandre Velho Prior, Ana Luísa Pereira Teixeira and Rui Manuel de Medeiros Melo Silva",downloadPdfUrl:"/chapter/pdf-download/73434",previewPdfUrl:"/chapter/pdf-preview/73434",authors:[{id:"50776",title:"Prof.",name:"Rui Manuel",surname:"de Medeiros Melo Silva",slug:"rui-manuel-de-medeiros-melo-silva",fullName:"Rui Manuel de Medeiros Melo Silva"},{id:"323528",title:"Dr.",name:"Ana Luísa",surname:"Pereira Teixeira",slug:"ana-luisa-pereira-teixeira",fullName:"Ana Luísa Pereira Teixeira"},{id:"323529",title:"Dr.",name:"Mariana",surname:"Gomes Morais",slug:"mariana-gomes-morais",fullName:"Mariana Gomes Morais"},{id:"328752",title:"Dr.",name:"Francisca",surname:"Guilherme Carvalho Dias",slug:"francisca-guilherme-carvalho-dias",fullName:"Francisca Guilherme Carvalho Dias"},{id:"328753",title:"Dr.",name:"João Alexandre",surname:"Velho Prior",slug:"joao-alexandre-velho-prior",fullName:"João Alexandre Velho Prior"}],corrections:null},{id:"75038",title:"Steroidal 5α-Reductase: A Therapeutic Target for Prostate Disorders",doi:"10.5772/intechopen.95809",slug:"steroidal-5-reductase-a-therapeutic-target-for-prostate-disorders",totalDownloads:74,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Neelima Dhingra",downloadPdfUrl:"/chapter/pdf-download/75038",previewPdfUrl:"/chapter/pdf-preview/75038",authors:[{id:"208896",title:"Dr.",name:"Neelima",surname:"Dhingra",slug:"neelima-dhingra",fullName:"Neelima Dhingra"}],corrections:null},{id:"74379",title:"Monoamine Oxidase A (MAO-A): A Therapeutic Target in Lung Cancer",doi:"10.5772/intechopen.95013",slug:"monoamine-oxidase-a-mao-a-a-therapeutic-target-in-lung-cancer",totalDownloads:58,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Chandreyee Datta, Sukhamoy Dhabal and Ashish Bhattacharjee",downloadPdfUrl:"/chapter/pdf-download/74379",previewPdfUrl:"/chapter/pdf-preview/74379",authors:[{id:"333538",title:"Dr.",name:"Ashish",surname:"Bhattacharjee",slug:"ashish-bhattacharjee",fullName:"Ashish Bhattacharjee"},{id:"338829",title:"Ms.",name:"Chandreyee",surname:"Datta",slug:"chandreyee-datta",fullName:"Chandreyee Datta"},{id:"338830",title:"Mr.",name:"Sukhamoy",surname:"Dhabal",slug:"sukhamoy-dhabal",fullName:"Sukhamoy Dhabal"}],corrections:null},{id:"73905",title:"Bulk and Nanocatalysts Applications in Advanced Oxidation Processes",doi:"10.5772/intechopen.94234",slug:"bulk-and-nanocatalysts-applications-in-advanced-oxidation-processes",totalDownloads:121,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Luma Majeed Ahmed",downloadPdfUrl:"/chapter/pdf-download/73905",previewPdfUrl:"/chapter/pdf-preview/73905",authors:[{id:"321806",title:"Prof.",name:"Luma",surname:"Majeed Ahmed",slug:"luma-majeed-ahmed",fullName:"Luma Majeed Ahmed"}],corrections:null},{id:"73576",title:"Oxidoreductases: Significance for Humans and Microorganism",doi:"10.5772/intechopen.93961",slug:"oxidoreductases-significance-for-humans-and-microorganism",totalDownloads:128,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Hussein Mahdi Kareem",downloadPdfUrl:"/chapter/pdf-download/73576",previewPdfUrl:"/chapter/pdf-preview/73576",authors:[{id:"321418",title:"M.Sc.",name:"Hussein Mahdi",surname:"Kareem",slug:"hussein-mahdi-kareem",fullName:"Hussein Mahdi Kareem"}],corrections:null},{id:"74857",title:"Neurodegeneration: Diagnosis, Prevention, and Therapy",doi:"10.5772/intechopen.94950",slug:"neurodegeneration-diagnosis-prevention-and-therapy",totalDownloads:109,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Mrinal K. Poddar, Apala Chakraborty and Soumyabrata Banerjee",downloadPdfUrl:"/chapter/pdf-download/74857",previewPdfUrl:"/chapter/pdf-preview/74857",authors:[{id:"318618",title:"Emeritus Prof.",name:"Mrinal K.",surname:"Poddar",slug:"mrinal-k.-poddar",fullName:"Mrinal K. Poddar"},{id:"318620",title:"Dr.",name:"Soumyabrata",surname:"Banerjee",slug:"soumyabrata-banerjee",fullName:"Soumyabrata Banerjee"},{id:"338670",title:"Ms.",name:"Apala",surname:"Chakraborty",slug:"apala-chakraborty",fullName:"Apala Chakraborty"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"6966",title:"Lipid Peroxidation Research",subtitle:null,isOpenForSubmission:!1,hash:"f1f45176e765ecb65a1c6d1496e75b5b",slug:"lipid-peroxidation-research",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/6966.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7499",title:"Kinetics of Enzymatic Synthesis",subtitle:null,isOpenForSubmission:!1,hash:"ec806ce44e877d1bd8d3dcbf1fbc2f3f",slug:"kinetics-of-enzymatic-synthesis",bookSignature:"Lakshmanan Rajendran and Carlos Fernandez",coverURL:"https://cdn.intechopen.com/books/images_new/7499.jpg",editedByType:"Edited by",editors:[{id:"35190",title:"Prof.",name:"Lakshmanan",surname:"Rajendran",slug:"lakshmanan-rajendran",fullName:"Lakshmanan Rajendran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"74443",slug:"corrigendum-to-fruit-flies-diptera-tephritoidea-biology-host-plants-natural-enemies-and-the-implicat",title:"Corrigendum to: Fruit Flies (Diptera: Tephritoidea): Biology, Host Plants, Natural Enemies, and the Implications to Their Natural Control",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/74443.pdf",downloadPdfUrl:"/chapter/pdf-download/74443",previewPdfUrl:"/chapter/pdf-preview/74443",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/74443",risUrl:"/chapter/ris/74443",chapter:{id:"29609",slug:"fruit-flies-diptera-tephritoidea-biology-host-plants-natural-enemies-and-the-implications-to-their-n",signatures:"M. A. Uchoa",dateSubmitted:"March 31st 2011",dateReviewed:"September 21st 2011",datePrePublished:null,datePublished:"February 24th 2012",book:{id:"874",title:"Integrated Pest Management and Pest Control",subtitle:"Current and Future Tactics",fullTitle:"Integrated Pest Management and Pest Control - Current and Future Tactics",slug:"integrated-pest-management-and-pest-control-current-and-future-tactics",publishedDate:"February 24th 2012",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/874.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"87919",title:"Dr.",name:"Manoel",middleName:null,surname:"Uchoa",fullName:"Manoel Uchoa",slug:"manoel-uchoa",email:"uchoa.manoel@gmail.com",position:null,institution:{name:"Universidade Federal da Grande Dourados",institutionURL:null,country:{name:"Brazil"}}}]}},chapter:{id:"29609",slug:"fruit-flies-diptera-tephritoidea-biology-host-plants-natural-enemies-and-the-implications-to-their-n",signatures:"M. A. Uchoa",dateSubmitted:"March 31st 2011",dateReviewed:"September 21st 2011",datePrePublished:null,datePublished:"February 24th 2012",book:{id:"874",title:"Integrated Pest Management and Pest Control",subtitle:"Current and Future Tactics",fullTitle:"Integrated Pest Management and Pest Control - Current and Future Tactics",slug:"integrated-pest-management-and-pest-control-current-and-future-tactics",publishedDate:"February 24th 2012",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/874.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"87919",title:"Dr.",name:"Manoel",middleName:null,surname:"Uchoa",fullName:"Manoel Uchoa",slug:"manoel-uchoa",email:"uchoa.manoel@gmail.com",position:null,institution:{name:"Universidade Federal da Grande Dourados",institutionURL:null,country:{name:"Brazil"}}}]},book:{id:"874",title:"Integrated Pest Management and Pest Control",subtitle:"Current and Future Tactics",fullTitle:"Integrated Pest Management and Pest Control - Current and Future Tactics",slug:"integrated-pest-management-and-pest-control-current-and-future-tactics",publishedDate:"February 24th 2012",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/874.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"5807",leadTitle:null,title:"Recent Improvements of Power Plants Management and Technology",subtitle:null,reviewType:"peer-reviewed",abstract:"Since first AC current high-power hydropower plant was put in operation, built by Nikola Tesla and George Westinghouse in 1895 on Niagara Falls, electrification of the world has dramatically changed. The growing power demand and energy consumption in the last decades require fundamental changes in the process, power production, and services. These requirements tend to use both conventional and nonconventional energy generation in order to have power plants economically useful and environmentally friendly to the society. The goal of this textbook is to provide an up-to-date review of this important topic with specific emphasis on the current guidelines for improving overall efficiency, lowering emissions, and using large share of renewable energy.",isbn:"978-953-51-3358-2",printIsbn:"978-953-51-3357-5",pdfIsbn:"978-953-51-4734-3",doi:"10.5772/65534",price:119,priceEur:129,priceUsd:155,slug:"recent-improvements-of-power-plants-management-and-technology",numberOfPages:200,isOpenForSubmission:!1,hash:"5f357d049b0e0c8d41243c794ef8d923",bookSignature:"Aleksandar B. Nikolic and Zarko S. Janda",publishedDate:"July 13th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5807.jpg",keywords:null,numberOfDownloads:8967,numberOfWosCitations:3,numberOfCrossrefCitations:0,numberOfDimensionsCitations:3,numberOfTotalCitations:6,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 28th 2016",dateEndSecondStepPublish:"October 19th 2016",dateEndThirdStepPublish:"January 15th 2017",dateEndFourthStepPublish:"April 15th 2017",dateEndFifthStepPublish:"June 14th 2017",remainingDaysToSecondStep:"4 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"19724",title:"Dr.",name:"Aleksandar",middleName:"B",surname:"Nikolic",slug:"aleksandar-nikolic",fullName:"Aleksandar Nikolic",profilePictureURL:"https://mts.intechopen.com/storage/users/19724/images/5117_n.jpg",biography:'Born in Belgrade, Serbia in 1966.\nBSc, MSc and PhD in electrical engineering in 1991,1999,2009 at University of Belgrade.\nSince 2005 Principal Technical Associate at Institute \\"Nikola Tesla\\". Project manager of several main projects at Institute.\nSince 2009 Head of Accredited Laboratory for Power Quality Testing at Institute Nikola Tesla.\nSince 2013 President of Scientific Council at Institute Nikola Tesla.\nSince 1998 IEEE Member, since 2006 IEEE Senior Member.\nSince 1995 Member of Serbian Power Electronics Society, since 2001 Member of the Board.\nSince 2001 Member of CIGRE Serbia technical committee B4 (HVDC and Power Electronics), since 2016 President of CIGRE Serbia technical committee B4.',institutionString:null,position:"President of Scientific Council",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],coeditorOne:{id:"151700",title:"Dr.",name:"Žarko",middleName:null,surname:"Janda",slug:"zarko-janda",fullName:"Žarko Janda",profilePictureURL:"https://mts.intechopen.com/storage/users/151700/images/5852_n.jpg",biography:"Zarko S. Janda was born in 1960. He received his Dipl. Ing., MSc, and PhD (power electronics) degrees in 1984, 1989, and 2004, respectively, from the School of Electrical Engineering, University of Belgrade, Yugoslavia, all in Electrical Engineering. He has been with the EE Institute “Nikola Tesla,” Belgrade, since 1984. He was an associate fellow at School of Electrical Engineering, University of Belgrade, Serbia, between 1993 and 2004. He was a professor at the High School of Professional Studies in Electrical Engineering and Computer Science, Belgrade, Serbia, between 2003 and 2010. Presently, he is a chairman of Serbian IEEE PES Chapter, chairperson of CIGRE-Serbia committee B4, and member of Board of the Serbian Power Electronics Society.\n\nContact: +381-64-8259-736, janda@ieent.org",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"803",title:"Power Plant Engineering",slug:"power-plant-engineering"}],chapters:[{id:"56217",title:"Introductory Chapter: Review of Current Research Trends in the Field of Power Plants",slug:"introductory-chapter-review-of-current-research-trends-in-the-field-of-power-plants",totalDownloads:777,totalCrossrefCites:0,authors:[{id:"19724",title:"Dr.",name:"Aleksandar",surname:"Nikolic",slug:"aleksandar-nikolic",fullName:"Aleksandar Nikolic"}]},{id:"54655",title:"Key Technical Performance Indicators for Power Plants",slug:"key-technical-performance-indicators-for-power-plants",totalDownloads:2498,totalCrossrefCites:0,authors:[{id:"139804",title:"Prof.",name:"Adela",surname:"Bara",slug:"adela-bara",fullName:"Adela Bara"},{id:"188586",title:"Dr.",name:"Simona Vasilica",surname:"Oprea",slug:"simona-vasilica-oprea",fullName:"Simona Vasilica Oprea"}]},{id:"55227",title:"Predictive Maintenance Based on Control Charts Applied at Thermoelectric Power Plant",slug:"predictive-maintenance-based-on-control-charts-applied-at-thermoelectric-power-plant",totalDownloads:1026,totalCrossrefCites:0,authors:[{id:"71214",title:"Prof.",name:"Željko",surname:"Đurović",slug:"zeljko-djurovic",fullName:"Željko Đurović"},{id:"198641",title:"Dr.",name:"Emilija",surname:"Kisic",slug:"emilija-kisic",fullName:"Emilija Kisic"},{id:"198751",title:"Dr.",name:"Vera",surname:"Petrovic",slug:"vera-petrovic",fullName:"Vera Petrovic"}]},{id:"54995",title:"Model Development for Analysis of Steam Power Plant Reliability",slug:"model-development-for-analysis-of-steam-power-plant-reliability",totalDownloads:886,totalCrossrefCites:0,authors:[{id:"196898",title:"Dr.",name:"Bernard Tonderayi",surname:"Mangara",slug:"bernard-tonderayi-mangara",fullName:"Bernard Tonderayi Mangara"}]},{id:"55841",title:"Risk Assessment of NPP Safety in Case of Emergency Situations on Technology",slug:"risk-assessment-of-npp-safety-in-case-of-emergency-situations-on-technology",totalDownloads:894,totalCrossrefCites:0,authors:[{id:"139600",title:"Prof.",name:"Juraj",surname:"Králik",slug:"juraj-kralik",fullName:"Juraj Králik"}]},{id:"55229",title:"Analysis of the Spatial Separation Effects of Thorium/Uranium Fuels in Block‐Type HTRs",slug:"analysis-of-the-spatial-separation-effects-of-thorium-uranium-fuels-in-block-type-htrs",totalDownloads:804,totalCrossrefCites:0,authors:[{id:"201457",title:"Dr.",name:"Ming",surname:"Ding",slug:"ming-ding",fullName:"Ming Ding"},{id:"201458",title:"Mr.",name:"Jie",surname:"Huang",slug:"jie-huang",fullName:"Jie Huang"}]},{id:"55019",title:"Spatial Aspects of Environmental Impact of Power Plants",slug:"spatial-aspects-of-environmental-impact-of-power-plants",totalDownloads:835,totalCrossrefCites:0,authors:[{id:"125578",title:"Dr.",name:"Bosko",surname:"Josimovic",slug:"bosko-josimovic",fullName:"Bosko Josimovic"},{id:"200736",title:"Dr.",name:"Sasa",surname:"Milijic",slug:"sasa-milijic",fullName:"Sasa Milijic"}]},{id:"54413",title:"Scalable, Self‐Contained Sodium Metal Production Plant for a Hydrogen Fuel Clean Energy Cycle",slug:"scalable-self-contained-sodium-metal-production-plant-for-a-hydrogen-fuel-clean-energy-cycle",totalDownloads:1252,totalCrossrefCites:0,authors:[{id:"199190",title:"Dr.",name:"Alvin",surname:"Stern",slug:"alvin-stern",fullName:"Alvin Stern"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"194665",firstName:"Mirena",lastName:"Calmic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/194665/images/4795_n.jpg",email:"mirena@intechopen.com",biography:"As a Commissioning Editor at IntechOpen, I work closely with our collaborators in the selection of book topics for the yearly publishing plan and in preparing new book catalogues for each season. This requires extensive analysis of developing trends in scientific research in order to offer our readers relevant content. Creating the book catalogue is also based on keeping track of the most read, downloaded and highly cited chapters and books and relaunching similar topics. I am also responsible for consulting with our Scientific Advisors on which book topics to add to our catalogue and sending possible book proposal topics to them for evaluation. Once the catalogue is complete, I contact leading researchers in their respective fields and ask them to become possible Academic Editors for each book project. Once an editor is appointed, I prepare all necessary information required for them to begin their work, as well as guide them through the editorship process. I also assist editors in inviting suitable authors to contribute to a specific book project and each year, I identify and invite exceptional editors to join IntechOpen as Scientific Advisors. I am responsible for developing and maintaining strong relationships with all collaborators to ensure an effective and efficient publishing process and support other departments in developing and maintaining such relationships."}},relatedBooks:[{type:"book",id:"6332",title:"Thermal Power Plants",subtitle:"New Trends and Recent Developments",isOpenForSubmission:!1,hash:"616ffd286d75ca988abf59b408880a98",slug:"thermal-power-plants-new-trends-and-recent-developments",bookSignature:"Pawe? Madejski",coverURL:"https://cdn.intechopen.com/books/images_new/6332.jpg",editedByType:"Edited by",editors:[{id:"179645",title:"Dr.",name:"Paweł",surname:"Madejski",slug:"pawel-madejski",fullName:"Paweł Madejski"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6838",title:"Power Plants in the Industry",subtitle:null,isOpenForSubmission:!1,hash:"5e647d27dab23e014dd8881ac3d5931c",slug:"power-plants-in-the-industry",bookSignature:"Tolga Taner",coverURL:"https://cdn.intechopen.com/books/images_new/6838.jpg",editedByType:"Edited by",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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:"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:"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:"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:"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:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],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"}}]},chapter:{item:{type:"chapter",id:"56811",title:"Use, Applications and Mechanisms of Intracellular Actions of Camelid VHHs",doi:"10.5772/intechopen.70495",slug:"use-applications-and-mechanisms-of-intracellular-actions-of-camelid-vhhs",body:'In 1993, Hamers-Casterman discovered the presence of heavy-chain-only antibodies in the sera of Camelidae and assessed that these antibodies are still capable of recognizing an extensive repertoire of antigens despite the absence of the light chain. Single-domain antibodies from camels are called nanobodies. They stated that this discovery could be of inestimable value to the development and engineering of soluble VH domains or new immunological molecules for diagnostic, therapeutic, and biochemical purposes [1]. This discovery gave rise to a whole new research field in which single-domain antibodies are used for a wide range of applications. Some of these will be reviewed in the current chapter.
The structural properties of conventional IgG antibodies are well known. These consist of two heavy-chain polypeptides and two light-chain polypeptides, each of which is folded into four and two domains, respectively. A variable domain is situated at the N-terminus of both chains (VH and VL) and, as the name suggests, its sequence diverges between IgG antibodies. Paired VH-VL domains make up the variable fragment (Fab) and are responsible for the recognition and binding of the target antigen. The sequence of the other domains is well conserved between IgGs, which led to the designation of these domains as constant domains. Heavy-chain-only antibodies differ from conventional IgG antibodies by the lack of a light-chain polypeptide and the first constant domain of the heavy-chain polypeptide (CH1). Consequently, the antigen-binding fragment of heavy-chain antibodies from camels consists of one single domain, termed the VHH domain. This unit forms the functional and structural equivalent of the Fab in conventional IgG antibodies [2]. The smallest antibody fragment that can be produced from conventional IgG antibodies is a short-chain variable fragment (ScFv, ±27 kDa), which consists of a VH and VL domain linked via a polypeptide. In the continuous search for smaller antibody formats, HCAbs were a thrilling novelty, because their discovery allowed researchers to produce an even smaller antibody fragment of only ±15 kDa. This antibody format derived from camels consists of an isolated VHH domain also known as a single-domain antibody or a nanobody (Nb) (Figure 1). In addition, human single-domain antibodies VH and VL have been engineered from human conventional antibodies [3, 4, 5], and sharks develop heavy-chain-only antibodies (HCAbs) too [6].
Schematic representation of a conventional IgG antibody and a camelid heavy-chain-only antibody (HCAb). For both antibody formats, the smallest producible antibody fragment is depicted: a short-chain variable fragment (ScFv, ±27 kDa) and a nanobody (Nb, ±15 kDa), respectively.
The structural features of nanobodies are quite similar to those of the variable domain of conventional IgGs. The core structure of the immunoglobulin domain is formed by four framework regions (FR), whereas antigen binding occurs through three complementarity-determining regions (CDRs). The latter are located in loops in between β-strands that form the variable immunoglobulin domain. Importantly, FR2 of the VHH domain often contains amino acid substitutions of residues that are involved in hydrophobic interactions between the VH and the VL domains of conventional IgGs (V37 → F/Y, G44 → E/Q, L45 → R, and W47 → G/F/L; Kabat numbering). These substitutions lie at the heart of the single-domain nature of nanobodies because they reduce the hydrophobicity of the former VL interface and improve the nonstickiness of the domain. There are other examples of amino acid substitutions that frequently take place, but these appear to be of less importance [7, 8]. Since nanobodies only consist of one domain, one might wonder whether nanobodies have a diverse antibody repertoire. After all, they lack the VH-VL combinatorial diversity in the antigen-binding site. Nanobodies have counterbalanced the absence of the three hypervariable loops of the VL domain by an
Several monoclonal antibodies (mAbs) have already been approved for clinical use [11], but some limitations are still present despite their success. This includes their large size, relative instability, which imposes restrictions on the administration route and their relative expense of manufacturing. The potential of nanobodies as a therapeutic agent was rapidly recognized as they overcome some of the aforementioned limitations of mAbs. The small size of nanobodies in combination with their extended CDR loops allows them to bind into clefts and cavities, whereas mAbs preferably recognize flat and concave surfaces. Many biological interactions take place in clefts, and nanobodies can target these otherwise inaccessible surfaces and thus function as neutralizing agents or antagonists of protein-protein interactions. More specifically, this property is advantageous when it comes to therapeutically targeting infectious diseases since the essential epitopes of pathogens are often hidden. When cancer has to be targeted, the small size permits a better tissue penetration and thus a significant improvement of the effective antibody concentrations that can be reached in solid tumors. Unfortunately, this advantageous property comes with a price. The small size of nanobodies results in their rapid clearance from the human body and thus in a limited in vivo half-life (a few hours). Therefore, nanobodies are often linked to a serum albumin-binding monomer to prolong serum half-life. The monomeric nature of nanobodies simplifies antibody engineering. For instance, nanobodies can be assembled into multimers, thereby increasing their potency due to avidity effects. The development of therapy resistance can also be curbed by creating bispecific nanobodies. The creation of a targeted drug delivery vehicle is also possible, since nanobodies can easily be linked with drugs [12, 13, 14, 15, 16, 17]. Additionally, the outstanding stability of nanobodies under extreme conditions opens the possibility to more patient-friendly routes of administration. In general, mAbs are administered via injections, but due to the extraordinary stability of nanobodies, they can be administered orally, topically, and even via inhalation [15, 18, 19]. The cost of nanobody production lies several times below those of mAb production. The fact that nanobodies are efficiently produced in microbial systems keeps the expenses low. Considering the fact that immunotherapy involves administration of relatively high doses of antibody during prolonged periods, this is a factor that should not be underestimated [7, 8, 20]. Currently, there are no nanobody-based products approved as therapeutic agent, but several products are in the pipeline or in advanced clinical trials. Their value in treating envenoming [21], infections [22], amyloidosis [23, 24], cancer, and other pathologies [25, 26] has already been proven. The research concerning the use of nanobodies as a therapeutic agent is mainly performed on extracellular targets. Nonetheless, nanobodies can also aid in identifying intracellular targets since they directly target a resident, endogenous protein, similar to how a conventional drug acts. RNAi-based approaches rather eradicate, or at least downregulate, expression which is quite different from the mode of action of an average drug. Hence, caution is warranted when making predictions regarding the therapeutic value of a given protein target using this approach. Moreover, nanobodies retain their functionality in the reducing intracellular environment. The major stumbling block toward a successful clinical implementation however is their inability to traverse the cell membrane. For that reason, most experiments are limited to cell cultures and transgenic animals. In the following paragraph, the use of nanobodies to target intracellular proteins with possible therapeutic implications will be described.
About 500 million people worldwide are chronically infected with hepatitis B virus or hepatitis C virus (HBV or HCV). Infection induces an acute and chronic inflammatory liver disease, which puts the patient at risk of developing liver cirrhosis and possibly hepatocellular carcinoma. Currently, there is no vaccine available against HCV, and there is also no cure for most people who are already infected with HBV [27]. Initially, therapy existed of a strict and intensive treatment with ribavirin and PEGylated interferon. This regimen was however associated with severe side effects [28], emphasizing the importance of further research into the pathogenesis of the viruses and how they evade our immune systems. Extensive research led to the discovery of direct-acting antivirals (DAAs), which are small compounds targeted against viral enzymes. The second-generation DAAs are highly potent in treatment, show less side effects, and have a less intensive treatment regimen [29]. However, during infection a large number of viral variants are continuously produced, resulting in the presence of
The potency of nanobodies for counteracting HCV infection has been evaluated. Several nonstructural HCV proteins have been targeted via nanobodies: NS5B, NS3, NS4A, and NS4B [28, 31, 32, 33]. NS5B functions as an RNA-dependent RNA polymerase. NS3 has a dual function and displays serine protease activity in its N-terminal region and helicase activity in its C-terminal region. The helicase is involved in the replication of the viral genome and is also thought to increase the translational efficiency of the polyprotein by melting highly stable secondary structures in the HCV RNA [34]. The N-terminal serine protease domain is, together with NS4A, involved in downstream processing of the HCV polyprotein with the formation of mature proteins [32]. NS4B plays a major role in HCV replication by inducing an ER membrane web on which HCV replication takes place [31]. Nanobodies against the different nonstructural proteins were obtained via screening of a VH/VHH library constructed from peripheral blood mononuclear cells of an 8-month-old naïve male dromedary. Recombinant nanobodies reduced NS5B activity by two-thirds (ELISA) [28], and NS3 helicase activity was inhibited up to 88–100% in the presence of the nanobodies, depending on the assay used [33]. Cell-based assays were performed on Huh7 cells (human hepatoma cell line) transfected with RNA (genomic replicon of heterologous HCV). The nanobodies also led to a significant reduction of HCV RNA levels in Huh7 cells transfected with the JFH1 genotype 2a strain, both inside the cells as in the culture medium, when compared to control conditions. Overall, the nanobodies were capable of eliciting responses of a magnitude similar as seen for conventional therapeutic strategies (ribavirin + PEGylated interferon or telaprevir) [28, 31, 32, 33]. Furthermore, treatment of cells with the nanobodies against NS3/NS4A and NS4B induced the expression of genes involved in the innate immune response (IRF3, IL28-B, and IFN-β). This is interesting because the innate immune response signaling is interrupted by the virus [31, 32]. In general, these studies lack a detailed insight into the molecular mechanisms behind the observed effects. The authors used computerized modeling to make an assumption about which epitopes are recognized by the nanobodies. Crystallization studies would allow a more detailed view and could help to resolve remaining questions. Even more, the crystal structures could lay the foundation for small molecule development and thus be invaluable. The nanobodies certainly have potential, but there are some remaining questions that need to be resolved before continuing with animal experiments.
As mentioned earlier, currently the biggest obstacle for using nanobodies as a therapeutic against intracellular targets is their inability to traverse cellular membranes. In the aforementioned articles, it was reported that coupling the nanobody with a cell-penetrating peptide (penetratin) seemingly promoted cellular uptake of the nanobody with efficiencies of roughly 80% [28]. However, some caution is warranted here, since the mechanisms behind the internalization of CPPs are still a matter of debate. Even more, in the highly cited article of Richard et al., it has been shown that experiments used to detect the occurrence of CPP internalization are sensitive to artifacts. It appeared that even mild fixation protocols used for fluorescence imaging can induce an artifactual redistribution of these peptides in the nucleus. Furthermore, the highly cationic nature of, for example, penetratin peptides lead to their strong binding to the overall negatively charged plasma membrane [35]. It is thus of crucial importance to remove membrane-bound peptide before analyzing cellular uptake of the construct. Initially, it was thought that CPPs allowed the delivery of biomolecules without relying on endocytosis. Adaptations of the used protocols, however, gave rise to data supporting an active process of cellular internalization involving endocytosis. Applications with CPPs and the controversial issues regarding their internalization mechanisms are elaborately reviewed and will not be discussed in detail [36, 37]. Internalization via endocytosis is however associated with a major drawback, since the delivered biomolecule needs to escape from the endosomal vesicles before it traffics back to the plasma membrane for recycling or it fuses with lysosomes. This might strongly limit the bioavailability of the compound, thus curbing its efficacy. Finally, the nonspecificity of CPP-conjugated constructs imposes a risk of drug-induced toxic effects on normal tissues [37]. In conclusion, a meticulous evaluation of intracellular uptake of the bioactive molecule and of possible toxic effects on normal tissues is warranted, before taking any further steps in its development as a therapeutic agent.
The genome of hepatitis B virus (HBV) is translated into HBV surface proteins, polymerase protein, X protein, or core and pre-core proteins [38]. Targeting the hepatitis B surface antigen (HBsAg) and the hepatitis B core antigen (HBcAg) with antiviral drugs to, respectively, reduce viral secretion and replication is a feasible strategy. HBsAg is the major component of the viral envelope. HBcAg, on the other hand, is the structural unit of the nucleocapsid that encloses the viral genome within a viral particle [38, 39].
To obtain nanobodies against the aforementioned proteins, a llama was immunized with recombinant HBcAg and HbsAg. The peripheral blood cells and cervical lymph node cells were used to construct a VHH library. Both immune and naïve libraries are good sources for retrieving antigen-specific binders. However, in general, superior binding affinities are observed for nanobodies originating from immune libraries, since they were subjected to in vivo affinity maturation. On the other hand, naïve libraries offer an elegant solution for those cases where immunization is difficult due to the lack of an antigen, low immunogenicity, or toxic antigens [39]. The nanobodies against HBsAg were cloned in frame with an ER-targeting signal and an ER retention signal. Co-transfection of these nanobodies and a HBV-expressing plasmid in HepG2 cells induced the intracellular accumulation of HBsAg and caused a reduction of HbsAg particle secretion of approximately 80–90%. The in vivo potential of the HBsAg nanobodies was examined in a SCID mouse. The mouse model for HBV infection was created using a hydrodynamics-based transfection method. Remarkably, measured HBsAg levels in the plasma decline in the presence of the nanobody, and this reduction goes hand in hand with an increase in intracellular HBsAg levels. This observation implies that less virions are secreted. The researchers assume that the observed effects are either due to the disruption of the interaction between the nucleocapsid and the S-type of viral membrane proteins or due to the prevention of the interaction between individual proteins in the ER [40].
The current anti-HIV treatment strategy, known as highly active antiretroviral therapy (HAART), has changed the field and has turned HIV into a chronic manageable disease. However, patients are lifelong bound to this regimen, its associated side effects, and drug-drug interactions. Sometimes, treatment fails due to multidrug resistance which warrants research for alternative drugs [41]. Nanobodies could serve as a useful purpose in the treatment of HIV infection and have been successfully raised against Rev and Nef. Rev is involved in the nuclear export of late viral mRNA to the cytoplasm. Rev multimers form a higher affinity complex with RRE (Rev-response element), and this affinity is a determining factor for the efficiency of RNA export [42, 43]. The idea of targeting Nef with antivirals came from the observation that a limited amount of patients, infected with Nef-deleted HIV, presented a lack of disease progression. The Nef protein exerts multiple functions: CD4 downregulation, major histocompatibility complex downregulation (MHC1), activation of p21-activated protein kinase (pak2), and enhancement of virion infectivity. These functions can be targeted each independently from one another since the activities are genetically separable. Interfering with Nefs’ capacity to downregulate CD4 appears to be the most effective strategy [44].
Vercruysse et al. produced nanobodies against the N-terminal multimerization domain of Rev, because its ability to form multimers is essential for its function. One nanobody is capable of efficiently inhibiting Rev multimerization in cell-based assays. The nanobody induces a cytoplasmic delocalization of Rev. that is similar to that observed for Rev mutants incapable of multimerization. In addition, the nanobody is able to suppress the Rev-dependent expression of late viral mRNAs and consequently also de novo virus production [42]. Further experiments were performed to elucidate whether the nanobody displays a broad-spectrum anti-HIV activity. This was examined by infecting several cell lines, expressing the nanobody in a stable manner, with different HIV-1 subtypes. Virus replication was monitored 5 days post infection by measuring cytopathogenic effects and the presence of virus-associated p24 levels in the supernatant. The nanobody strongly reduced p24 levels for infected cells compared to a control nanobody. More specifically, p24 levels were reduced by >10 folds for subtype A, > 100 folds for subtypes C and G, and >10,000 folds for subtypes B, D, and H [45]. The cells proved to be resistant to viral replication and survived infection. These results are relevant, considering the fact that subtypes A, B, and C are the most prevalent genetic forms on a global scale [46].
Bouchet et al. picked Nef, a HIV-1 nonstructural protein, as target for antiviral therapy. Using cell-based assays and in vivo assays, it was established that the Nef-specific nanobody efficiently counteracted Nef-induced CD4 downregulation and p21-activated protein kinase (pak2) activation. The functional effects of the nanobody are thought to result from its interference with the interaction between Nef and other cellular partners [47]. Nef-induced CD4 downregulation in infected cells is important to prevent interaction between the envelope protein (Env) of the budding virion and CD4 of the host cell, since this interaction might impede the formation of fully infectious particles [44]. The nanobody is capable of reducing the rate of Nef-induced CD4 internalization back to levels measured in uninfected cells. The biological relevance of this observation was tested in a mouse model (CD4+/HIV Nef Tg mouse) that presents a downregulation of cell surface CD4, an altered thymic CD4 T-cell development, and a profound peripheral CD4 T-cell depletion. The nanobody rescued the Nef-mediated thymic CD4+ T-cell maturation defect and reversed the downregulation of cell surface CD4 in vivo. T-cell receptor signaling normally leads to profound actin cytoskeleton rearrangements. The Nef-pak2 complex, however, halts these rearrangements by deregulating cofilin, an actin-severing factor. Actin polymerization in infected T cells is thus strongly disturbed. The nanobody disrupts the Nef-Pak2 complex and counteracts as such the inhibition of actin remodeling in a dose-dependent manner. Finally, it was also observed that the inhibition of specific Nef functions by the nanobody resulted in the reduction of virus infectivity of new progeny virions by 80% (molar ratio of 1:1) [47].
Current HAART targets four different steps in the HIV-1 replication circle: the conversion of viral genomic RNA into dsDNA, the maturation of budding viral particles, the entry of the virus into new target cells, and the insertion of viral DNA into a host cell chromosome. Although current strategy is effective, it remains important to explore novel treatment strategies. The development of compounds that inhibit less explored drug targets would be of benefit, and structural biology can aid in defining new drug targets [48]. Nanobodies targeted against both Rev. and Nef appear to have pronounced effects on pathogeny of HIV-1. Crystallization studies to elucidate the exact binding epitopes for both nanobodies are thus of paramount importance since they could aid in new small compound design.
There exists a multitude of antimicrobial drugs, but compounds capable of neutralizing the produced toxins are often lacking. The question whether or not antibodies hold great potential as toxin-neutralizing agents has been investigated by several researchers. Examples of studies where monoclonal antibodies are used as antitoxins are listed in the review of Chow et al. [49]. Several researchers have exploited nanobodies as a means to neutralize toxins. Intrabodies have been employed to counteract following toxins: ricin,
Ricin is a naturally occurring toxin derived from the castor bean plant and a well-known type 2 ribosome-inactivating protein. It achieves an inhibition of eukaryotic ribosomes by the depurination of a specific adenine in the 28S ribosome resulting in cell death. Exposure might be lethal, and unfortunately current treatments are mainly of a symptomatic and supportive nature [50]. Herrera et al. constructed a bispecific nanobody, named JJX12, consisting of a VHH targeted against the enzymatic subunit of ricin coupled with a VHH targeted against the galactose-binding subunit [51]. JJX12 fully protects mice against a ricin challenge (molar ratio of 4:1). The protective effects observed for the bispecific construct are superior to those observed for an equimolar mixture of the nanobodies and are the result of both extracellular and intracellular effects. JJX12 promotes aggregation of ricin in solution and makes cell-bound ricin-JJX12 complexes more resistant to dissociation as shown by ricin competition assays with lactose [51]. In the presence of these complexes, further ricin binding to the cell surface is reduced by shielding cell surface receptors for the galactose-binding subunit of ricin [52]. The presence of aggregates changes the internalization and intracellular trafficking of ricin. Internalization of the aggregates occurs via a macropinocytosis-like mechanism rather than via receptor-mediated clathrin-dependent and clathrin-independent endocytosis, which is normally observed for ricin. Furthermore, biochemical and live cell imaging techniques showed a 54% reduction of the retrograde transport of ricin to the trans-Golgi network and the accumulation of ricin in late endosomes in the presence of JJX12, which probably targets ricin for degradation [51].
Salmonella bacteria are Gram-negative enterobacteria associated with human enteric fever. The systemic virulence of the bacterium is largely dependent on the SpvB gene, encoding an actin ADP-ribosylating toxin that is secreted into the host cell cytosol. The toxin interferes with actin polymerization resulting in apoptotic cell death. Nanobodies targeted against the SpvB protein are capable of blocking its enzymatic and cytopathic effects. By means of in vitro radioactivity and fluorescence assays, it was demonstrated that the nanobody completely rescues actin polymerization from the inhibitory effects of the SpvB toxin at a molar ratio of 1:1. Cell-based assays, performed on RAW macrophages and Vero cells, confirmed these observations, since cells exposed to the toxin presented no signs of cell rounding or actin cytoskeleton disintegration in the presence of the nanobody [53].
Botulinum neurotoxins (BoNTs) produced by the Gram-positive bacterium
Kuo et al. made a fusion protein between a nanobody and a truncated F-Box protein (TrCP) that is capable of associating with Skp1 and Cullin1, with the formation of the SCF complex. This complex, called targeted F-box (TFB), functions as an E3 ubiquitin ligase, thus targeting BoNT proteases for proteasomal degradation. Two constructs were made in which a nanobody targeted against either A-Lc or B-Lc was incorporated. The TFB fusion proteins reduce A-Lc and B-Lc levels with 65 and 50%, respectively (capture ELISA experiments), and decrease the half-life of the A-Lc protease (from ̴3.7 to ̴1.5 days). Application of MG132, a proteasome inhibitor, results in the accumulation of poly-ubiquitinylated BoNT protease and eliminates the effect of the TFB fusion proteins on its steady-state levels. This indicates that the observed effects are due to the increased degradation of the BoNT protease. Furthermore, in the presence of the TFB fusion proteins, cells are less sensitive to BoNT-A intoxication and also recover 2.5 times faster [54].
Proteins exert crucial roles in a variety of cellular processes. Each of these proteins has to adopt its native tridimensional structure to acquire the functional biological state and thus to act faultlessly. However, sometimes proteins fail to either fold correctly or to maintain the native state due to the presence of mutations or increased protein levels. When these proteins escape the inherent quality control systems, serious diseases can develop. These disorders can be characterized by the deposition of misfolded peptides or proteins in the nervous system or other tissues and organs resulting in pathological and insoluble aggregates.
Preventive and curative treatments are often lacking. These therapeutic approaches are feasible when using nanobodies as a tool: increasing the stability of the correctly folded proteins, neutralization of toxic protein/peptide species, and inhibiting or reversing the aggregation of misfolded proteins into oligomers or fibrils [56]. Several research groups have already exploited the use of nanobodies for targeting protein misfolding diseases [57, 58, 59]; however, most of the time, they aim at extracellular targets. We will focus on the intracellular application of nanobodies.
Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease characterized by an extended N-terminal poly-alanine stretch of polyadenylate-binding protein nuclear 1 (PABPN1). The poly-alanine stretch is extended from 10 to 12–17 alanines. The mutant protein forms aggregates in skeletal muscles, and this phenomenon is, at least in part, responsible for the disease, although the exact pathological mechanisms are still poorly understood. PABPN1 is a multifunctional protein and is involved in pre-mRNA polyadenylation, transcription regulation, and mRNA nucleocytoplasmic transport [56].
Verheesen et al. screened a nonimmune VHH library for PABPN1-selective binders. Panning yielded six nanobodies with affinities ranging between 5 and 57 nM. Initial experiments were performed with nanobody 3F5 (Kd = 5 nM), which binds PABPN1 at its N-terminal coiled-coiled domain. Co-transfection of mutant PABPN1 and nuclear targeted 3F5 (3F5-NLS) in HeLa and COS cells showed a dose-dependent reduction in the formation of aggregates (37% → 10% in HeLa cells, P < 0.01). The expression of the nanobody neither induces cytotoxic effects (MTT assay) nor has any effects on mutant PABPN1 expression levels [60]. A more in-depth analysis on how the formation of intranuclear inclusions is prevented revealed that the nanobody reduces the formation of oligomers of mutant PABPN1 but not of insoluble aggregates [61]. The in vivo efficiency of the six nanobodies was tested in a
Gelsolin amyloidosis is an autosomal dominant disease for which currently only symptomatic treatment strategies exist. A point mutation in the GSN gene (G654 A/T) is responsible for the incorrect folding of the secondary domain of mutant gelsolin (D187 N/Y) that adopts a protease-sensitive conformational state. A pathological proteolytic cascade involving furin and MT1-MMP like proteases leads to the secretion of amyloidogenic 8 and 5 kDa peptides in the extracellular matrix and thus to the formation of extracellular deposits [63]. Van Overbeke et al. used gelsolin nanobodies to shield mutant plasma gelsolin (PG) from aberrant furin cleavage [24]. Furin is a membrane-associated pro-protein convertase that is ubiquitously expressed. It cleaves mutant PG as it passes through the trans-Golgi network (TGN) and generates a C-terminal 68 kDa fragment (C68) that is secreted into the extracellular matrix [63]. This initial step in the amyloidogenic cascade is targeted using a Nb that binds mutant PG near the furin cleavage site with low nanomolar affinity (10 nM, in the presence of Ca2+). In vitro experiments demonstrated a dose-dependent decrease of mutant PG cleavage. The C68 signal intensity is reduced by 76% (P < 0.001) when a twofold molar excess of Nb is added. In cell-based assays, the nanobody drastically reduced secretion of C68 in the cell medium. The in vivo efficiency of the nanobody was further analyzed in a gelsolin amyloidosis/nanobody double-positive mouse model expressing human mutant PG. The Nb not only positively affects transgenic mutant gelsolin proteostasis in skeletal muscle tissue but also attenuates the decrease in contraction speed of the extensor digitorum longus in an 8-min fatigue protocol [24]. Using adeno-associated virus as a vehicle, a bispecific nanobody was introduced in these mice that protects against both furin and MT1-MMP, yielding similar effects on muscle contraction speed [64, 65]. Inhibiting the enzymatic activity of furin could be an alternative strategy, and noncompetitive furin-inhibiting nanobodies have been identified although they have not been tested for treatment of gelsolin amyloidosis [66]. However, despite the involvement of furin in several pathological processes, some considerations have to be made regarding its use as a therapeutic target. Although a complete/partial cleavage redundancy of furin toward several substrates was observed in the liver of an interferon-inducible Mx-Cre/loxP, furin knockout mouse model and obvious adverse effect were absent; a complete knockout of furin in a mouse model resulted in embryonic lethality at day 11 [67, 68]. This observation probably precludes their use in chronic treatments because it is rather unlikely that the long-term inhibition of furin does not go hand in hand with severe adverse effects. Therefore, shielding mutant PG from aberrant cleavage seems to be the better strategy. Moreover, this approach is already successfully implemented in the treatment of early-stage familial amyloid polyneuropathy caused by amyloidogenic variants of transthyretin, thus highlighting its feasibility [69].
Over the years, nanobodies have earned their mark as a research tool. A variety of extracellular and intracellular applications using nanobodies exist, and the latter will be discussed here. Intrabodies are often used to unravel protein functions and to gain insight into their dynamics. The versatility of nanobodies and the ease by which they can be engineered allow researchers to use different lines of approach (Figure 2). Chromobodies, consisting of a nanobody fused with a fluorescent protein, allow researchers to recognize and trace endogenous proteins in living cells [70]. Since they are already well known, they will not be discussed in detail here.
Schematic overview of nanobody-based applications in research. Upper panel.
Nanobodies are an attractive tool for the determination of endogenous protein function. They not only complement well-known RNAi and CRISPR/Cas9 techniques but also allow a more detailed insight by pinpointing specific functions with “surgical precision” by targeting individual protein domains (rather than eliminating the entire protein altogether) and protein conformations, which cannot be achieved by expression modulation. In other words, nanobodies can be of inestimable value to deepen our knowledge of several biological pathways. Researchers have employed several strategies for assessing the functionality of proteins or protein domains, and the different options will be discussed here.
As stated earlier, nanobody cDNAs are available, and these are easily engineered. This implies that the addition of a delocalization tag is fairly straightforward. A variety of targeting sequences are available and can be used to induce the enrichment of both nanobody and its target at specific (ectopic) subcellular compartments. This strategy allows researchers to assess the interaction between the nanobody and its target in the strongly reducing intracellular environment and thus to confirm the in vivo functionality of nanobodies. Moreover, in this way, one can also disturb protein function by restricting free diffusion of the protein and limiting its availability at places where it is needed [71]. Considering that the paratope of the nanobody is located at its N-terminal end, it is safer to fuse the tag at the C-terminal end of the nanobody. Otherwise, a substantial risk at disturbing antigen binding exists [2], although there are examples where a long tag is added to the nanobody N-terminus without disturbing its functionality [72]. Beghein et al. elegantly demonstrated how effectively nanobodies can delocalize their target protein to a variety of subcellular organelles. A survivin Nb (Kd ~ 1 nM) was capable of guiding endogenous survivin in or out the nucleus (
Some nanobodies exert a direct inhibitory effect, resulting in a functional knockout of the protein. These nanobodies can help researchers to define the biochemical activities of proteins. For example, mechanistic insights in podosome formation were revealed by two inhibitory nanobodies targeted against L-plastin (LPL). LPL Nb5 is capable of blocking the actin-bundling activity of L-plastin, and LPL-Nb9 locks LPL in an inactive conformation. Experiments involving these nanobodies revealed the participation of L-plastin (LPL) in podosome formation and stability [75]. Furthermore, L-plastin is a component of cancer cell invadopodia and contributes to matrix degradation and cancer cell invasion. These effects are mediated by the actin-bundling activity of L-plastin and its bundling independent role in MMP9 secretion and activity, as revealed by the differential effects observed in the presence of LPL Nb5 and LPL Nb9 [76]. One can also interfere with signaling pathways by specific inhibition of the transcriptional activity of proteins, like beta-catenin and p53 [77, 78]. These nanobodies can be used to elucidate the impact of cofactors and post-translational modifications on the targeted protein and allow us to broaden our understanding of the respective signaling pathways. Insight into pathological mechanisms, which might result in the identification of druggable targets, can also be obtained. For example, nanobodies were used to investigate the role of two enzymatic domains of TcdB, a toxin produced by
Finally, nanobodies are known to stabilize certain protein conformations and are often used as an aid in crystallization experiments [2]. This property also comes in handy when one wants to study the mechanisms by which cellular receptors translate extracellular cues into intracellular responses. Depending on which conformation the receptor adopts after ligand binding, certain downstream signaling events can be either activated or inhibited. Staus et al. have identified nanobodies that preferentially recognize and stabilize the β2 adrenergic receptor in its active or inactive conformation resulting in a variety of functional effects [80]. These experiments indicate that nanobodies, by acting as an allosteric modulator of receptors, can help us to understand receptor biology.
An alternative way to determine the function of a protein of interest (POI) in an in vivo setting is to selectively induce their degradation and study the resulting knockout phenotype. To achieve this goal, three different groups have exploited a combination of nanobodies and the endogenous ubiquitin proteasome pathway, a system that is responsible for selective protein degradation in eukaryotes [81, 82, 83]. Caussinus et al. were the first to use the ubiquitin pathway for targeted degradation by making adaptations of an E3 ubiquitin ligase, more specifically the cullin-RING 1 (CLR1) E3 ligase complex. For this purpose, a fusion between the F-box domain of
Just like DeGradFP, the cullin-RING E3 ubiquitin ligases were used as the framework for synthetic E3 ligase design. In an attempt to enhance the E3 activity, however, the GFP Nb was fused directly to a truncated adaptor protein instead of the substrate recognition protein. The best results were obtained with Ab-SPOP, a synthetic version of the CLR3 E3 ligase complex, displaying a 10-fold stronger signal reduction of a GFP-tagged protein compared to DeGradFP (50-fold vs. 5-fold). Importantly, the construct degrades only nuclear proteins, and possibly in the future, similar constructs may become available that degrade cytoplasmic proteins. The in vivo effectiveness of Ab-SPOP was confirmed in zebra fish embryos. Ab-SPOP-induced depletion of Hmg2a-citrine, a protein responsible for the modulation of nucleosome and chromatin structure, resulted in various early developmental defects [83]. Fulcher et al. tailored the von Hippel-Lindau (VHL) protein as an affinity-directed protein missile, called AdPROM. Under normoxic conditions, this substrate recognition protein recruits the hypoxia-inducible factor (HIF1α) to the CLR2 E3 ligase. AdPROM is composed of a fusion between the VHL protein and a GFP Nb. It was of crucial importance that the GFP Nb was positioned at the C-terminus of the VHL protein in order to obtain a proper orientation of the target proteins to the CLR2 E3 ligase complex. Since the paratope of a nanobody is localized at the N-terminal end, one should definitely check for potential detrimental effects of this fusion on the binding capacity of the nanobody itself. However, the affinity-directed protein missile was competent in inducing the specific degradation of GFP-tagged VPS34 and PAWS1 proteins in human cell lines, which was further substantiated by the observation of functional effects. Interestingly, during these experiments the researchers observed the co-degradation of UVRAG which is a regulatory component of the VPS34 kinase complex. This suggests that AdPROM has the potential of destroying protein complexes although only individual proteins are targeted [82]. Targeted degradation of proteins of interest by the use of nanobodies holds great potential and might be the perfect complement to CRISPR/Cas systems or RNAi in the elucidation of protein function. The tunability of this system is a huge benefit. Future experiments should point out whether the GFP Nb can be replaced by highly selective nanobodies targeted against specific proteins. In this way, one could investigate the functions of the protein of interest in a more direct manner, without the requirement of protein tags.
Nanobodies can be utilized for the detection of protein-protein interactions in cell-based assays. There is a large supply of in vitro methods which can be used for the detection of protein-protein interactions. These methods are widely used and highly efficient for high-throughput screenings but are limited by the fact that they don’t operate in intact mammalian cells. Screening for interaction between proteins in their native environment guarantees their proper folding and the presence of necessary cofactors or regulatory proteins. Both nanobody-based methods rely on the interaction between a GFP Nb and a GFP-tagged protein. Herce et al. covalently linked a GFP Nb with a protein that accumulates at a specific subcellular location. In mammalian cells, this protein could be, for example, laminin B1 or centrin, which results in the delocalization of the GFP Nb to the nuclear lamina or the cytoplasmic centrioles, respectively. Subsequently, a GFP-tagged protein will be recruited to a specific location. If the second protein of interest, labeled with another fluorophore, interacts with the first protein of interest, the fluorophores will co-localize at a discrete spot. This interaction can be visualized by a single-fluorescence snapshot. Interestingly, this technique also allows screening for inhibitors of protein-protein interactions [84]. Another recently developed technique uses biocompatible engineered upconversion nanoparticles (UCNPs) conjugated with GFP Nbs. Visualization of the interaction between two proteins of interest is based on the lanthanide resonance energy transfer (LRET). As a proof of concept, they probed for the indirect interaction between the mitochondrial proteins TOM20 and TOM7. The latter was expressed as a fusion protein with EGFP and the former as a fusion protein with dsRed and a Halo tag. This Halo tag was subsequently labeled with tetramethylrhodamine (TMR), while the EGFP was recognized by the GFP Nb-labeled UCNPs. Co-localization of both proteins results in the detection of LRET-sensitized TMR emission. Remarkably, TOM7 and TOM20 are spatially separated by TOM40. The capacity of this technique for reporting indirect long-distance interactions might be of interest to unravel cellular protein complexes [85].
Nanobodies are highly versatile tools with interesting biochemical properties, which result in their application in various fields ranging from basic research and diagnostics to therapy. In this chapter, we aim to shed light on their multifunctionality and in this way encourage other researchers to include this technology in their future projects. Since their discovery in 1993, the numbers of publications wherein nanobodies are employed are gradually increasing which indicate that their merit has been proved. Here, we have shown that nanobodies have a high therapeutic potential and form an ideal stepping stone to drug development. Despite isolated cases, nanobodies are not capable of traversing the cellular membrane, preventing their direct use as a therapeutic. The effects observed with nanobody treatment are established through multiple mechanisms. Nanobodies can act as an inhibitor of enzymatic activity, interfere with specific protein-protein interactions, and shield a protein of interest from aberrant cleavage, or they can be used as a tool to target proteins for proteasomal degradation. We believe that effects triggered by nanobodies in vitro or in vivo are a faithful representation of what to expect with conventional pharmacological drugs, since both compounds directly target the resident endogenous protein. However, since current experiments are often limited to cell-based assays, animal experiments are warranted to confirm their effectiveness. Furthermore, nanobodies have a lot to offer as a research tool. They can help researchers to elucidate protein functions and thereby gain insight in biological pathways. Several strategies are possible, ranging from subcellular delocalization to the induction of protein knockouts. Last but not least, nanobodies may represent an adequate answer to problems encountered with (conventional) antibody reproducibility [86, 87]. Indeed, particularly polyclonal antibodies run out of stock at some point in the future, making experimental verification impossible. Because nanobody cDNAs are readily obtained and researchers all over the world can use exactly the same nanobody in their experiments, problems of reproducibility can be reduced. In the future, we hope to stimulate a closer consultation within the nanobody field and by doing so taking the research to the next level.
This work was supported by grants from the Research Foundation Flanders (Fonds Wetenschappelijk Onderzoek (FWO) Vlaanderen) and Ghent University (BOF13/GOA/010). AS and LB are supported by the Agency for Innovation by Science and Technology in Flanders (IWT-Vlaanderen). We apologize to those researchers whose work could not be cited.
Flooding has caused, and is still responsible for, most of the world’s biggest humanitarian crises. It affects a large number of people through displacement from their homes, physical drowning, psychological trauma, and, in extreme cases, death. It is responsible for some of the largest economic and environmental losses in different places around the world. Recent data from the United Nations Office for Disaster Risk Reduction show that, on average, 250 million people globally are affected by flooding each year. Disaster modeling team at Aon Benfield estimates the global economic cost of flooding at over USD 90 billion and predicts an increase that will exceed USD 500 billion by 2030. Although flooding is a global phenomenon, the experience in the developing countries (DCs) is an important research issue, which reflects particularly the need to bolster action toward mitigating the human and environmental impacts.
\nThe attribution of flooding largely reflects a variety of factors, which includes at least, rapid urban growth, the development of coastal cities, sea level rises, and poor planning ideology to accommodate fast-paced urban development. Climate change is also high on the chain of attribution of flood risk. Extant research (e.g., [1, 2, 3]) reveals that climate change is escalating the frequency of low- to high-duration high intensity rainfall events, which is the main trigger of pluvial urban flooding in recent times. Within a global context, the poorest and least-prepared communities are subject to large-scale impacts of these events, which also undermine their potential to develop economically while they aim to mitigate the loss of human lives and development efforts. In case of sea level rises, climate change has over time forced a cumulative rise in the global sea level that now compromises the usual structural defenses up to 1 in 1000-year flooding.
\nSimple techniques based on appropriate flood risk management concepts can save lives and reduce losses. This includes the use of modern technology, which utilizes geospatial infrastructure to identify and map areas prone to flooding and to inform appropriate action toward disaster preparedness, rescue, and recovery. This is more of a United Nations International strategy on Disaster reduction (UNISDR) concept of living with floods rather than fighting them. The principles underlying this concept are the importance of building communities’ resilience to recurrent flooding events. Evidence from best practices in flood risk and disaster management reveals that building communities’ resilience to flooding reflects two main factors: the establishment of timely warning systems and adequate investment in key infrastructure, with sustainable development initiatives [4, 5, 6].
\nEarly warning systems, through communication of flood risk assessment and uncertainties, are important to improve the communities’ preparedness and to help them make better decisions for their safety [7, 8]. This is a good step toward reducing human and economic impacts of flooding. However, the studies of Fakhruddin et al. [9] and Smith et al. [10], which both focused on community-based flood of early warning systems in Asia, suggest that the implementation early warning systems and communication of flood assessment in the DCs raise vital research discussions. This is now more crucial than ever with the increasing human development on the coastal areas of these DCs, along with the rate of investments in risk management and public infrastructure, which does not resonate well with a formidable sustainable development initiatives. Of course, sustainable development can build-up the emergency response and rescue currency and assist in meeting the challenges that occur much later, such as epidemics, loss of infrastructure and displacement of people from their homes. It is obvious that real development of urban centers makes significant and dominant contributions toward building communities’ resilience to flooding. However, Cohen [11] underlined a major issue that is often overlooked in this regard, which relates particularly to how to give communities in the DCs the needed capacities to thrive amidst the formidable sustainable development challenges.
\nThe experience of flooding in Nigeria provides some interesting insights into these challenges, the limitations in early warning systems, and how communities’ lack of capacities to thrive amidst formidable sustainable development affects their resilience to flooding. Sadly, more than 4 years since the Sendai framework replaced its predecessor, Hyogo, the resilience of many communities in Nigeria to flooding is still a major issue. Of course, there are success stories here and there; however, the increase in human and economic damages caused by floods and the inability of communities to recover from the effects of floods, despite years after the disaster, indicate some asymmetries in the concept of resilience. This chapter aims to address these issues which offer significant insights into the current debates in flood disaster management. It outlined a number of specific challenges to building communities’ resilience to flood disasters in Nigeria. The experiences of communities in Lokoja, Kogi state, which were affected during the 2012 flood in Nigeria, are explored to provide useful insights into the shortcomings in early warning systems and development processes in Nigeria and how they affect communities’ resilience to flooding. The chapter raised issues related to community participation, risk-based investment, and rural adaptation programs, all of which can be advocated to facilitate community resilience and coping capacity to all variants of flood hazards in Nigeria.
\nThe idea of flood-related resilience was initially the core argument of De Bruijn [12], who proposed a system approach as a new perspective whose prospect was to evolve a flood risk management that fits well with the socioeconomic context in which the management of flood disasters occurs. Within the system approach, the author contrasted resistance strategies—which aim at flood prevention—with resilience strategies, which aim at minimizing flood impacts and enhancing the recovery from those impacts. Resistance measures such as the primitive engineering structures to hold back the surges of water can be illustrated as a dredge of the old wineskin. However, the new paradigm in disaster management subject to UNISDR has introduced a fresh insight into the weakness of resistance measures and thus paves the way for resilience strategies. Although those engineering structures are still being used today, their main ideology is to build the resilience of communities to flood disaster.
\nResilience thinking provides new beachheads for a comprehensive flood disaster management for both rural and urban communities. Cutter et al. [13] were of the opinion that resilience is a set of capacities that can be mediated through initiatives and policies, which help build and enhance communities’ capacities to respond to and recover from disasters. Communities that employ resilience strategy, rather than resistance measures, are able to better cope with the uncertainties of flood disaster. Norris et al. [14] perceived community resilience as a process that relates a range of adaptive capacities to responses and changes after adverse events. Speaking of this capacity, core flood-related resilience research based their arguments on how to solve mostly disturbance and disasters induced by climate change (e.g., [13, 15]). However, there is a different view of flood-related resilience in which resilient houses and critical infrastructure are emphasized with different engineering parameters such as robustness and flexibility. Using pluvial flooding in the DCs as the exemplar, Jiang et al. [16] presented the China’s sponge city initiative in relation to contemporary understanding of sustainable urban stormwater management. This is a novel flood-related resilience framework with an emphasis on structural design in which the efficiency of the stormwater management system is related to community’s flood-related resilience. Kahan et al. [13, 17] reported more recent research on resilience from a homeland security perspective, which is aimed primarily at protecting critical infrastructure from terrorism. Resilience from the point of view of homeland’s security of critical infrastructure assumes that resilience is an outcome measure with an end goal of damage and loss mitigation, as well as recovery from a distorted state.
\nA useful approach to the discussion of what constitutes flood-related resilience is to understand its foundations. Alexander [18] made etymological statements on the concept of resilience. The study attempted to link current perspectives of resilience to its original ideas explored by the author in the field of science, humanities, law, and politics. The study revealed that the concept of resilience benefits from a good history of meaning and application, although defining resilience from a continuum of ideas can lead to complex theories and to define a particular problem area, say flood disaster management can be slightly ambiguous. However, with the understanding that flood risk in DC is associated with a complex range of attributions, the concept of resilience may be useful to poll a multidisciplinary interest, towards overcoming limitations in improving flood risk management strategies. It is for this reason that in order to mitigate the current problems with flooding crisis in Nigeria, research should try to understand how the history and background of resilience affect building a bespoke flood-related resilience in Nigeria. Further, from a more political point of view, it is instructive to elucidate the extent to which different actors are involved, drawing from a variety of training, career orientations, and management practices in Nigeria that can contribute to the prospect of building a flood-related resilience for Nigerians. This is an important discussion to the extent in which this chapter makes the case for investing in flood risk and community participation, which endow a somewhat statutory responsibility on both the public and private organizations in Nigeria and the need to integrate flood resilience into urban planning as proposed by Bertilsson et al. [19].
\nBeyond the historical underpinnings of resilience and its implications for managing flood disaster, other important areas of current discussion that are crucial for building Nigeria’s flood-related resilience are (1) the metrics and standards to measure resilience that remain challenging according to Cutter et al. [13] and (2) the issue of “resourcing,” which is the central theme in the discourse of resilience that it has been seen to restore life at the foundation of a community’s capacity to recover from disasters [20]. These aspects of resilience are not common in many studies that have considered flood resilience and vulnerability in Nigeria, for example, Ajibade et al. [21] and Nkwunonwo [22], and these are issues that need to be addressed. In the world of resilience research, the indicators of resilience construct are often difficult to determine, and this is an important issue for Nigeria. Quasin et al. [23] and Shah et al. [24] in a flood resilience study for Pakistan selected a number of indicators of flooding from the literature search and found their proxies from preliminary data collected from a questionnaire. This gives a significant motivation as much as provides an insight into how this chapter intends to bridge the knowledge gaps in resilience studies in Nigeria.
\nEarly warning systems (EWSs) and a general developmental initiative are crucial in the success of disaster risk mitigation [25]. Various studies and extensive literature have shown that EWS in particular contributes to the resilience of societies to disaster and is therefore supported by various disaster management strategies [7]. Similarly, initiative toward developmental infrastructure, which includes public health facilities, microfinance institutions and insurance companies, effective communications systems and good traffic networks for easy connectivity, safe drinking water, public housing scheme, proper waste management and sanitation facilities, public recreation facilities, green spaces, community centers, geospatial data platforms, quality internet-of-things (IoT), sustainable drainage systems (SUDS), resilient houses, etc., can facilitate preparedness, emergency response, rescue, and recovery—relating to a disaster management framework—as well as enhance the resilience of communities toward disaster reduction. Speaking of floods, evidence from a growing body of scientific research indicates that the frequency of occurrence of extreme events, which possess potential for large-scale impacts, is much higher in recent times and likely to increase over the coming decades as a consequence of global climate change [3, 26, 27]. This fact cannot be more obvious; due to the inexorable nature of these disasters which suggest that risk reduction concepts are the only possible solution therefore, modern disaster mitigation techniques must take advantage of opportunities in meteorological forecasting as well as the development and implementation of EWS that targets vulnerable regions and populations. Much improvement in technical skill and conceptual understanding of weather and climatic events including the phenomenal El Niño/Southern Oscillation, which has eased freely into advanced forecast and predictions, offers sentiments and impetus to early warning for disaster management [28]. However, a major developmental limitation still remains to be addressed in early warning for disaster prediction in developing countries such as Nigeria.
\nVarious research opinions and empirical issues in global environmental change and science of the total environment reveal that flood risk and disaster scenarios of many urban conurbations and coastal areas have been predicted in advance, at least until 2050 [29, 30]. More than ever before in the history of man and the universe, knowledge of these predictions and their prospects to warn about future expectations is a crucial component of sustainability science. Rapid urbanization and population growth with the fast-growing coastal areas pose critical challenges, which must be addressed as part of disaster management strategy. Thus, there is a huge scientific undercurrent to the idea of resilience especially as it relates to floods that are often considered to be the worst hazard component within the human-ecological systems. Interestingly, this issue is not limited to environmental and geophysical scientists. In fact, reading through the discussions from the work of Ebi and Schmier [28], since the last 15 years, public health professionals have taken the opportunities of EWS to integrate weather- and climate-related information into local and regional risk management plans to reduce the detrimental health effects of extreme weather events, particularly tropical cyclones, floods, wildfires, and droughts. It is also worth noting that financial experts have a long-standing commitment to financial crises on the knowledge of EWS using certain
Nigeria’s 2012 flooding event has been the most devastating in over 40 years. The floods affected more than a third of the states of the federation and account for mass casualty and hundreds of thousands of internally displaced people (IDP). Its economic impact amounts to millions of US dollars in economic products and farmlands, which were either destroyed or rendered without any commercial values. There were epidemics of water-borne diseases in many states leading to declaration of “state of emergency” by the presidency. Since the event, with the exception of news reports and tabloid coverage, numerous local and international research groups have focused on the attribution, impacts, and implications of the flooding event as well as related disaster risk reduction and national development [32, 33, 34]. Figure 1 is a graphical representation of the experience and impacts of 2012 flooding events in Kogi.
\nImages of the 2012 flooding in Kogi state, Nigeria. Source: Google images of Nigeria’s Kogi 2102 flooding.
Although the flood disaster affected the whole of Nigeria, Kogi state is the most affected. The geography and the natural landscape of the state, which include the spectacular Niger-Benue confluence and the abundance of inland waterways and contiguous land-water boundaries, make the area prone to flooding. A geospatial-assessment carried out by Aderoju et al. [35] revealed that the 2012 flood disaster in Kogi led to the displacement of about 300,000 people within 37 communities in seven local government areas (LGAs). Many farmlands were washed away. Urban and rural settlements were devastated leaving dozens and dozens of residents in immediate needs of rehousing or resettlement. Despite the large-scale impacts of the event, evidence from especially Richard et al. [36], who examined the characteristic pattern of the response of major stakeholders during the Kogi flood disaster, Danjibo Nathaniel et al. [37], who identified the issues with rehabilitation and post-disaster housing reconstruction, and Adaji et al. [38], who illustrated the fall out of the flooding event in Kogi, revealed that the majority of the victims are still in serious crises, and that there are significant issues of uncertainty regarding the overall recovery process from flood damage in Nigeria. There is no doubt that the very nature of this unfortunate situation raises a number of real and unambiguous questions and opinions about the state of disaster management in Nigeria. It stimulates critical dialog on flood disaster resilience, which broadens into adaptation and coping capacity and overtly implicates early warning systems and the unique policies in Nigeria pertaining to disaster preparedness and recovery.
\nSpeaking of preparedness in respect of Kogi’s experience of the 2012 flooding, Idowu and Zhou [39] argued that the devastating effects of the 2012 flooding for the whole of Nigeria have been due to limitations in flood monitoring and a lack of an effective early flood warning system in the country. Indeed, Nigeria has yet to evolve efficient flood monitoring and early warning techniques given that the current available data on rainfall are mostly “hourly amounts,” which underestimate the intensity-duration-frequency (IDF) parameter needed in flood monitoring [40]. This data sparse situation, which according to Nkwunonwo et al. [33] constrains the application of more scientific approaches to flood risk management such as flood modeling and vulnerability assessment, is a major technical barrier to establish efficient early warning system in Nigeria. Two other important technical barriers are the lack of accurate flood assessment models to communicate the risk of flooding to a general population and epistemic uncertainties surrounding the warning issued by flood management agencies in Nigeria. Through its mainstay hydrological and meteorological institutions, for example, the NIMET (Nigeria Meteorological Agency) and NIHSA (Nigeria Hydrological Services Agency), Nigeria has monitoring and early warning systems in place, but their effectiveness and robustness, as well as the uncertainty surrounding warnings given prior to extreme weather events, are vital issues. Early warning systems are often used to alert communities of an imminent flooding event or any other hazard as the case may be, but also served as positive and proactive instruments that foster the reduction of the impacts of flooding on a community through knowledge and awareness of the causes and impacts of flooding [38]. Arguably, how these objectives relate to Nigeria’s situations is still under investigation.
\nOttah’s [41] study—with the main purpose being to identify the impact of early warning on the people of Ibaji—illustrates one of the crucial lessons from Kogi’s experience of flooding that will highlight the limitations of Nigeria’s EWS. Ottah [41] examined the warnings issued by Kogi radio before, during, and after the flood, which aims to raise awareness about floods and to urge residents of the River Niger bank to evacuate. Using a quantitative approach that sampled randomly 622 respondents from the population (127,572), the study found that almost all (100%) the residents listened to Kogi radio. However, while the majority (86.7%) heard of flood warnings on Radio Kogi, about 60% of the residents did not take warnings in preparation for the flood. Some of the respondents (44.7%) stated that the impact of the message was only average, while a few others (25.7%) said that the message failed to inspire any instincts or flight. Few respondents (45.6%) felt that Kogi radio should follow a communication strategy that would change the residents’ behavior and attitude. In fact, the results of this study raise the question of why the 2012 floods have had a major impact on residents, despite the fact that everyone has access to a source of warning information (namely the Kogi radio). So, what is the overall impact of EWS in the context of Nigeria’s flood-related resilience? How can EWS be developed to reflect on the cultural, social, and demographic profile of Nigerian communities? These are very important issues now being considered in the literature to improve on EWS for flood-related issues [42].
\nAdaji et al. [38] attributed the failure of flood early warnings in Nigeria to a number of social and technical barriers. First, the study argued that the failure was largely due to the fact that many of the flood disaster victims were unaware of floods. This is in addition to the general limitations in the adopted method of disaster response, rescue, and relief operations in Nigeria. This sheds light not only on the particular issues of social and demographic profile of residents and how it affects the effectiveness of early warning in Nigeria in terms of building communities’ resilience to floods, but also on the technical aspects of warning system needed to establish accuracy, reliability, and trust. Alfa et al. [43] conducted a study to identify socioeconomic factors that may influence the effectiveness of early warning systems by using their relationships with knowledge about the causes of flooding in rural areas of Kogi State, Nigeria. Cross-sectional study was conducted in 325 households in Oforachi using quantitative data collection methods. The
The success of early warning and preparedness in disaster management depends largely on the effectiveness of risk communication, and this is an area of concern with regard to Kogi’s experience of 2012 flooding but also explains the level of Nigeria’s risk communication profile. Sjoraida and Anwar [44] and Ogie et al. [45] raised two important issues that can elucidate the risk communication prospects and challenges in Nigeria. In particular, Sjoraida and Anwar [44] underlined the importance of integrating various communication methods to make risk communication more effective. Based on the study, effective risk communication must include traditional, modern, and digital communication systems. Similarly, Ogie et al. [45] identified the problem of risk communication in culturally and linguistically diverse communities. This is an issue that may explain the level of impact of the 2012 floods in many Kogi communities. In the context of these studies, one has to take a critical view of Nigeria’s risk communication, and, particularly in the light of the findings of Ottah [41], why residents respond with a
Kogi’s experience of the 2012 flooding also explains, in addition to the lack of early warning systems, the particular scenarios of investment in risk reduction, community participations, and rural adaptation toward flood-related resilience in Nigeria. There are a number of studies (e.g., [33, 47, 48]) that are more specific on these issues. Evidence from these studies suggests that these issues in their present state are a consistent syndrome, which collectively interferes with the overall success of Nigeria’s flood disaster management. Drawing from the UN disaster risk reduction program that is often responsive to community involvement and sustainable risk investment, one can quickly realize the need to rewrite and redefine Nigeria’s disaster management policy. The present top-bottom ideology should be replaced with a system that allows communities to speak on any aspect of flood risk management. The economic aspects of flood risk management should be part of the annual budget. In the Netherlands, floods and water management schemes are a statutory Dutch policy, which is one of the factors that makes flood risk management in the Netherland one of the most elaborate and in the world. While this may not be sustainable in Nigeria, entrepreneurs—small and medium—and many multinational companies should be encouraged to see the importance of investing in solving the flood problems in Nigeria. In fact, while the issues of urban sprawl and rural-urban drift are being addressed as both political and economic agenda, often at the expense of sustainable human development and environmental management, the problem of risk-based investment and community participation which are the core of the contemporary approaches of disaster management should not be ignored.
\nFlooding in Nigeria has been an important issue. Viewed from a global perspective, Nigeria is in the top 20 countries with current and future flood risk scenarios (including climate change and socioeconomic exposure and vulnerability to mostly coastal flooding) that are issues of grave concern. Besides the flooding of 2012 that is the central focus of discussions in this chapter, there has been series of flooding events in Nigeria that have severely impacted human lives and economic development. Historically, flooding in Nigeria dates back to the early 1950s and has affected mostly the coastal regions and places characterized as highly urbanized. Nkwunonwo [49] reviewed flood risk in Nigeria and found that within the period of 1985–2014, flooding has affected more than 11 million lives with a total of 1100 deaths and property damage exceeding US$17 billion. The study also found that Lagos state has experienced most of the floods, while more frequent floods are recorded in Niger, Kaduna, Cross River, Adamawa, Oyo, Kebbi, Kano, and Jigawa, hypothesized to be influenced by the rivers Niger, Benue, Ogun, and Hadejia [33, 50, 51]. These findings are validated by a 50-year flood hotspot analysis and mapping that identifies areas that seem more prone to flooding in Nigeria (see Figure 2).
\nHotspots of flooding in Nigeria. Source: Nkwunonwo et al. [
Fluvial, coastal and flash, and pluvial flooding events are major part of Nigeria’s flood history, and they have been a major cause of concern for rural areas and cities within the country [52, 53]. Fluvial flooding is being influenced by seasonal interruption of major rivers and the overflow of water, which overtops their natural and artificial defenses and overflows into areas not typically submerged. Adebayo and Oruonye [54] and Obeta [55] argued that fluvial flooding in Nigeria accounts for the majority of the hazard threats experienced in locations along the plains adjoining the major rivers in the country. The worst episode of fluvial flooding in Nigeria reported by Jeb and Aggrawal [56] was the Kaduna flood disaster of 2006, which resulted from heavy rainfall and dam collapse and flooded a whole community affecting more than 1000 families and 500 homes. The economic impact of the event was up to 3 billion naira ($35.45 million). As well as fluvial floods, coastal and flash floods in Nigeria affect the low-lying areas in the southern part of the country (e.g., Lagos, Oyo, Ondo, Akwa Ibom, and Bayelsa states). The social and economic impacts of these floods in Nigeria have been severe due to the number of human populations exposed as well as the economic growth within especially the coastal areas, which in recent times has increasingly become a source of attraction for urban development [49]. What seem to complicate discussion of flooding in Nigeria in recent times are the pluvial floods, which are the most prevalent types of floods in recent times and affect mainly the urban areas. These floods are influenced by heavy rainfall, which overwhelms the capacity of local drainage systems and soil infiltration potentials. Kogi state demonstrates the uniqueness of flooding typology in Nigeria as communities within the area have been subject to all known types of flooding in Nigeria. This is a situation that might explain why flooding impacts have been severe, and why it is important to consider the means to raise efficient early warning systems toward building the resilience of communities within the area.
\nThe long history of flooding in Nigeria with its spatial and temporal variability offers a ground to interrogate any possible changes in the meteorological context of the country. Within climate and ecology research, there is compelling evidence to show that Nigeria has experienced long-term changes in meteorological conditions, which is a strong foundation for the increasing exposure and vulnerability to flooding and other health hazards within the country. One of the important studies, which examined meteorological changes in Nigeria, was carried out by Tarhule and Woo [57]. This study examined crucial changes in several rainfall characteristics (such as annual total rainfall and number of rainy days, the dates of onset, termination and duration of the rainy season, as well as monthly rainfall, monthly number of rainy days, and various categories of rainfall above certain intensities) in the northern Nigeria. Using rainfall records at 25 locations, which were analyzed for the occurrence of abrupt changes and trends on the basis the Pettitt and the Mann-Kendall tests, result showed, inter alia, the abrupt change in the time series of annual rainfall, number of rainy days, and affected areas north of latitude 11° N. Abdussalam et al. [58] revealed that certain variations in climatic variables such as daily maximum temperature, relative humidity, and sunshine are the most important explanatory influence on monthly meningitis incidence in the Northwest Nigeria. Other studies, which examined this variability, are Ogolo and Adeyemi [59], Obioha [60], and Shiru et al. [61]. The general importance of the evidence in these studies is the reality of long-term meteorological variations and how it influences more recent hazard events particularly flooding in Nigeria. Knowledge of these variations from more global models, such as Hirabayashi et al. [2] and Winsemius et al. [3], shows that the effects of meteorological variations on global flood risk scenarios are likely going to worsen in the future. Thus, current research should give priority toward enhancing the resilience of communities to flooding, especially by kindling interests for more effective warning systems.
\nKogi’s experience of the 2012 floods, especially the recovery part for the victims, provides an important lesson that is still a major topic in political and academic affairs. Within the academics, a number of studies have developed in the risk and disaster literature to improve the current knowledge of flood risk and management in Nigeria. The scarcity of geospatial data that are an integral part of limitations in Nigeria’s flood disaster management is now being addressed through international research collaborations and accessed to burgeoning open source geospatial data infrastructure. Evidence from current Lagos state flood risk management which Adelekan [62] outlined in a systematic review of policies, countermeasures and principles towards mediating the catastrophic effects of flooding in Nigeria. Some of the policies outlined are initiatives which focused on long- and short-term objectives, which include health reform, infrastructure development, water and land resource management, capacity development, strengthening of institutions, and various disaster management agencies across the country, collaborating with international partners such as OCHA (United Nations Office for the Coordination of Humanitarian Services), International Federation of Red Cross and Red crescent communities (IFRC) for aids, emergency relief assistance, and formulating ways to meet the urgent needs of people internally displaced by flooding. Meanwhile, according to various reports by IFRC, there is a number of ongoing long- and short-term courses of action to address the endogenous humanitarian crises brought about by flooding in Kogi floods and elsewhere in Nigeria. Literally, these efforts, which are being motivated by the Kogi’s flooding experience, promote collaborative flood disaster management. However, Adekola and Lamond [63] found that collaborative flood disaster management in Nigeria, which is essential to build community resilience to floods, must engage the governments, communities, businesses, multilateral, and nongovernmental organizations.
\nDebates on flood-related resilience are important and have long attracted interest in research, business, and political negotiations. Globally, these discussions are a call to action to alleviate the growing socioeconomic risks of flooding. Despite the great nature of these discussions, developing countries (DCs), for example, Nigeria, may still be ill-equipped to meet the minimum objectives of flood risk management especially as it pertains to building the resilience of communities, which the now defunct Hyogo framework for action capitalized on. Although Hyogo has been successfully replaced by SENDAI, the need to build community resilience as of now has not been redacted from disaster management. This less attention to community resilience has been demonstrated in Nigeria in relation to flood experiences. Undoubtedly, floods are virulent, cause massive loss, damage to natural resources, and affect the global economy, and these are the causes of concern in global disaster management. However, for Nigeria, uncertainty about how to mitigate flooding implies the need for extensive research to address the problem of increasing human vulnerability and highlights the potential for exploration if the aim of building a flood-related community resilience will ever be achieved. This chapter has opened a window into these discussions and in the main focus of building resilience to flood-related disasters in Nigeria, it outlines research strategies from a global perspective and important components of the SENDAI program for disaster reduction:
The substantial reduction of all forms of flood risk including direct losses in lives, livelihoods, and health and in the economic, physical, social, cultural, and environmental assets of persons, businesses, and communities; damage to critical infrastructure and disruption of basic services within Nigeria is the primary role of Nigeria and Nigerians alone. To make it more effective, this responsibility should be shared among the various tiers of government, the private and public sectors, donor agencies, international partners, local communities, and concerned citizens.
Reduction of these losses should be based on an understanding of disaster risk in all its dimensions of vulnerability, capacity, exposure of persons and assets, hazard characteristics, and the environment. Such knowledge can be used in the development of resilience and to widen the number of communities with adequate and sustainable support to complement their local actions for implementation of flood disaster risk reduction strategies.
Improving on the current method of flood risk assessment and governance at the national, state, and community levels should be imperative. This should reinforce the general flood disaster management framework in Nigeria, which includes preparedness, mitigation, response, and recovery.
There is urgent need to prioritize the development of, increase the availability of, and access to sustainable flood hazard early warning systems and flood disaster risk information and assessments to the general population. In order to “build back better and quicker” from flood disasters, the Nigerian government must contemplate integrating flood disaster risk reduction measures into development plans.
Building the economic, social, health, and cultural resilience of the general population and local communities should prompt public and private investment in flood disaster risk prevention and reduction through structural and nonstructural measures.
The author declares no conflict of interest.
These Terms and Conditions outline the rules and regulations pertaining to the use of IntechOpen’s website www.intechopen.com and all the subdomains owned by IntechOpen located at 5 Princes Gate Court, London, SW7 2QJ, United Kingdom.
',metaTitle:"Terms and Conditions",metaDescription:"These terms and conditions outline the rules and regulations for the use of IntechOpen Website at https://intechopen.com and all its subdomains owned by Intech Limited located at 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK.",metaKeywords:null,canonicalURL:"/page/terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
\\n\\nThe following terminology applies to these Terms and Conditions, Privacy Statement, Disclaimer Notice, and any or all Agreements:
\\n\\n“Client”, “Customer”, “You” and “Your” refers to you, the person accessing this website and accepting the Company’s Terms and Conditions;
\\n\\n“The Company”, “Ourselves”, “We”, “Our” and “Us”, refers to our Company, IntechOpen;
\\n\\n“Party”, “Parties”, or “Us”, refers to both the Client and ourselves, or either the Client or ourselves.
\\n\\nAll Terms refer to the offer, acceptance, and consideration of payment necessary to provide assistance to the Client in the most appropriate manner, whether by formal meetings of a fixed duration, or by any other agreed means, for the express purpose of meeting the Client’s needs in respect of provision of the Company’s stated services/products, and in accordance with, and subject to, the prevailing laws of the United Kingdom.
\\n\\nAny use of the above terminology, or other words in the singular, plural, capitalization and/or he/she or they, are taken as interchangeable.
\\n\\nUnless otherwise stated, IntechOpen and/or its licensors own the intellectual property rights for all materials on www.intechopen.com. All intellectual property rights are reserved. You may view, download, share, link and print pages from www.intechopen.com for your own personal use, subject to the restrictions set out in these Terms and Conditions.
\\n\\nWe employ the use of cookies. By using the IntechOpen website you consent to the use of cookies in accordance with IntechOpen’s Privacy Policy. Most modern day interactive websites use cookies to enable the retrieval of user details for each visit. On our site, cookies are predominantly used to enable functionality and ease of use for those visiting the site.
\\n\\nIn no circumstances shall IntechOpen or its suppliers be liable for any damages (including, without limitation, damages for loss of data or profit, or due to business interruption) arising out of the use, or inability to use, the materials on IntechOpen's websites, even if IntechOpen or an IntechOpen authorized representative has been notified orally or in writing of the possibility of such damage. Some jurisdictions do not allow limitations on implied warranties, or limitations of liability for consequential or incidental damages; consequently, these limitations may not apply to you.
\\n\\nIntechopen.com website content and services are provided on an "AS IS" and an "AS AVAILABLE" basis. Material appearing on www.intechopen.com could include minor technical, typographical, or photographic errors. IntechOpen may make changes to any material contained on its website at any time without notice.
\\n\\nIntechOpen has no formal affiliation to any external sites that link to www.intechopen.com, unless otherwise specifically stated. As such, it is not responsible for content that appears on any such sites. The inclusion of any link to IntechOpen does not imply endorsement by IntechOpen. Use of any such linked website is done solely at the user's own discretion.
\\n\\nWe reserve the right of ownership over our entire website www.intechopen.com, and all contents. By using our services, you agree to remove all links to our website immediately upon request. We also reserve the right to amend these Terms and Conditions and our linking policy at any time. By continuing to link to our website, you agree to be bound to, and abide by, these linking Terms and Conditions.
\\n\\nIf you find any link on our website, or any linked website, objectionable for any reason, please Contact Us. We will consider all requests to remove links but will have no obligation to do so.
\\n\\nWithout prior approval and express written permission, you may not create frames around our web pages or use other techniques that alter in any way the visual presentation or appearance of our website.
\\n\\nIntechOpen may revise its Terms of Service for its website at any time without notice. By using this website, you are agreeing to be bound by the current version of all Terms at the time of use.
\\n\\nThese Terms and Conditions are governed by and construed in accordance with the laws of the United Kingdom and you irrevocably submit to the exclusive jurisdiction of the courts in London, United Kingdom.
\\n\\nCroatian version of Terms and Conditions available here
\\n"}]'},components:[{type:"htmlEditorComponent",content:'By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
\n\nThe following terminology applies to these Terms and Conditions, Privacy Statement, Disclaimer Notice, and any or all Agreements:
\n\n“Client”, “Customer”, “You” and “Your” refers to you, the person accessing this website and accepting the Company’s Terms and Conditions;
\n\n“The Company”, “Ourselves”, “We”, “Our” and “Us”, refers to our Company, IntechOpen;
\n\n“Party”, “Parties”, or “Us”, refers to both the Client and ourselves, or either the Client or ourselves.
\n\nAll Terms refer to the offer, acceptance, and consideration of payment necessary to provide assistance to the Client in the most appropriate manner, whether by formal meetings of a fixed duration, or by any other agreed means, for the express purpose of meeting the Client’s needs in respect of provision of the Company’s stated services/products, and in accordance with, and subject to, the prevailing laws of the United Kingdom.
\n\nAny use of the above terminology, or other words in the singular, plural, capitalization and/or he/she or they, are taken as interchangeable.
\n\nUnless otherwise stated, IntechOpen and/or its licensors own the intellectual property rights for all materials on www.intechopen.com. All intellectual property rights are reserved. You may view, download, share, link and print pages from www.intechopen.com for your own personal use, subject to the restrictions set out in these Terms and Conditions.
\n\nWe employ the use of cookies. By using the IntechOpen website you consent to the use of cookies in accordance with IntechOpen’s Privacy Policy. Most modern day interactive websites use cookies to enable the retrieval of user details for each visit. On our site, cookies are predominantly used to enable functionality and ease of use for those visiting the site.
\n\nIn no circumstances shall IntechOpen or its suppliers be liable for any damages (including, without limitation, damages for loss of data or profit, or due to business interruption) arising out of the use, or inability to use, the materials on IntechOpen's websites, even if IntechOpen or an IntechOpen authorized representative has been notified orally or in writing of the possibility of such damage. Some jurisdictions do not allow limitations on implied warranties, or limitations of liability for consequential or incidental damages; consequently, these limitations may not apply to you.
\n\nIntechopen.com website content and services are provided on an "AS IS" and an "AS AVAILABLE" basis. Material appearing on www.intechopen.com could include minor technical, typographical, or photographic errors. IntechOpen may make changes to any material contained on its website at any time without notice.
\n\nIntechOpen has no formal affiliation to any external sites that link to www.intechopen.com, unless otherwise specifically stated. As such, it is not responsible for content that appears on any such sites. The inclusion of any link to IntechOpen does not imply endorsement by IntechOpen. Use of any such linked website is done solely at the user's own discretion.
\n\nWe reserve the right of ownership over our entire website www.intechopen.com, and all contents. By using our services, you agree to remove all links to our website immediately upon request. We also reserve the right to amend these Terms and Conditions and our linking policy at any time. By continuing to link to our website, you agree to be bound to, and abide by, these linking Terms and Conditions.
\n\nIf you find any link on our website, or any linked website, objectionable for any reason, please Contact Us. We will consider all requests to remove links but will have no obligation to do so.
\n\nWithout prior approval and express written permission, you may not create frames around our web pages or use other techniques that alter in any way the visual presentation or appearance of our website.
\n\nIntechOpen may revise its Terms of Service for its website at any time without notice. By using this website, you are agreeing to be bound by the current version of all Terms at the time of use.
\n\nThese Terms and Conditions are governed by and construed in accordance with the laws of the United Kingdom and you irrevocably submit to the exclusive jurisdiction of the courts in London, United Kingdom.
\n\nCroatian version of Terms and Conditions available here
\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:5820},{group:"region",caption:"Middle and South America",value:2,count:5289},{group:"region",caption:"Africa",value:3,count:1761},{group:"region",caption:"Asia",value:4,count:10546},{group:"region",caption:"Australia and Oceania",value:5,count:909},{group:"region",caption:"Europe",value:6,count:15932}],offset:12,limit:12,total:119318},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"20"},books:[{type:"book",id:"10672",title:"Nonlinear Optics",subtitle:null,isOpenForSubmission:!0,hash:"cfe87b713a8bee22c19361b86b03d506",slug:null,bookSignature:"Dr. Boris I. Lembrikov",coverURL:"https://cdn.intechopen.com/books/images_new/10672.jpg",editedByType:null,editors:[{id:"2359",title:"Dr.",name:"Boris",surname:"Lembrikov",slug:"boris-lembrikov",fullName:"Boris Lembrikov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10674",title:"Topics on Quantum Information Science",subtitle:null,isOpenForSubmission:!0,hash:"d7481712cff0157cd8f849cba865727d",slug:null,bookSignature:"Prof. Sergio Curilef and Dr. Angel Ricardo Plastino",coverURL:"https://cdn.intechopen.com/books/images_new/10674.jpg",editedByType:null,editors:[{id:"125424",title:"Prof.",name:"Sergio",surname:"Curilef",slug:"sergio-curilef",fullName:"Sergio Curilef"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10852",title:"Electromagnetic Compatibility",subtitle:null,isOpenForSubmission:!0,hash:"f5d2cce3a2adbd5d108d3301ee97025b",slug:null,bookSignature:"Dr. Ahmed Kishk",coverURL:"https://cdn.intechopen.com/books/images_new/10852.jpg",editedByType:null,editors:[{id:"150146",title:"Dr.",name:"Ahmed",surname:"Kishk",slug:"ahmed-kishk",fullName:"Ahmed Kishk"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10921",title:"Plasma Science and Technology",subtitle:null,isOpenForSubmission:!0,hash:"c45670ef4b081fd9eebaf911b2b4627b",slug:null,bookSignature:"Dr. Aamir Shahzad",coverURL:"https://cdn.intechopen.com/books/images_new/10921.jpg",editedByType:null,editors:[{id:"288354",title:"Dr.",name:"Aamir",surname:"Shahzad",slug:"aamir-shahzad",fullName:"Aamir Shahzad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10956",title:"Pulsed Lasers",subtitle:null,isOpenForSubmission:!0,hash:"88bd906b149fc3d1c5d6fdbd9916826c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10956.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:28},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:9},{group:"topic",caption:"Business, Management and Economics",value:7,count:3},{group:"topic",caption:"Chemistry",value:8,count:11},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:10},{group:"topic",caption:"Engineering",value:11,count:25},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:4},{group:"topic",caption:"Materials Science",value:14,count:7},{group:"topic",caption:"Mathematics",value:15,count:3},{group:"topic",caption:"Medicine",value:16,count:48},{group:"topic",caption:"Neuroscience",value:18,count:3},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:4},{group:"topic",caption:"Psychology",value:21,count:5},{group:"topic",caption:"Robotics",value:22,count:2},{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:5},popularBooks:{featuredBooks:[],offset:0,limit:12,total:null},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9154",title:"Spinal Deformities in Adolescents, Adults and Older Adults",subtitle:null,isOpenForSubmission:!1,hash:"313f1dffa803b60a14ff1e6966e93d91",slug:"spinal-deformities-in-adolescents-adults-and-older-adults",bookSignature:"Josette Bettany-Saltikov and Gokulakannan Kandasamy",coverURL:"https://cdn.intechopen.com/books/images_new/9154.jpg",editors:[{id:"94802",title:"Dr.",name:"Josette",middleName:null,surname:"Bettany-Saltikov",slug:"josette-bettany-saltikov",fullName:"Josette Bettany-Saltikov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7030",title:"Satellite Systems",subtitle:"Design, Modeling, Simulation and Analysis",isOpenForSubmission:!1,hash:"b9db6d2645ef248ceb1b33ea75f38e88",slug:"satellite-systems-design-modeling-simulation-and-analysis",bookSignature:"Tien Nguyen",coverURL:"https://cdn.intechopen.com/books/images_new/7030.jpg",editors:[{id:"210657",title:"Dr.",name:"Tien M.",middleName:"Manh",surname:"Nguyen",slug:"tien-m.-nguyen",fullName:"Tien M. Nguyen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10201",title:"Post-Transition Metals",subtitle:null,isOpenForSubmission:!1,hash:"cc7f53ff5269916e3ce29f65a51a87ae",slug:"post-transition-metals",bookSignature:"Mohammed Muzibur Rahman, Abdullah Mohammed Asiri, Anish Khan, Inamuddin and Thamer Tabbakh",coverURL:"https://cdn.intechopen.com/books/images_new/10201.jpg",editors:[{id:"24438",title:"Prof.",name:"Mohammed Muzibur",middleName:null,surname:"Rahman",slug:"mohammed-muzibur-rahman",fullName:"Mohammed Muzibur Rahman"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10413",title:"A Collection of Papers on Chaos Theory and Its Applications",subtitle:null,isOpenForSubmission:!1,hash:"900b71b164948830fec3d6254b7881f7",slug:"a-collection-of-papers-on-chaos-theory-and-its-applications",bookSignature:"Paul Bracken and Dimo I. Uzunov",coverURL:"https://cdn.intechopen.com/books/images_new/10413.jpg",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"}},{type:"book",id:"9515",title:"Update in Geriatrics",subtitle:null,isOpenForSubmission:!1,hash:"913e16c0ae977474b283bbd4269564c8",slug:"update-in-geriatrics",bookSignature:"Somchai Amornyotin",coverURL:"https://cdn.intechopen.com/books/images_new/9515.jpg",editors:[{id:"185484",title:"Prof.",name:"Somchai",middleName:null,surname:"Amornyotin",slug:"somchai-amornyotin",fullName:"Somchai Amornyotin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8148",title:"Investment Strategies in Emerging New Trends in Finance",subtitle:null,isOpenForSubmission:!1,hash:"3b714d96a68d2acdfbd7b50aba6504ca",slug:"investment-strategies-in-emerging-new-trends-in-finance",bookSignature:"Reza Gharoie Ahangar and Asma Salman",coverURL:"https://cdn.intechopen.com/books/images_new/8148.jpg",editors:[{id:"91081",title:"Dr.",name:"Reza",middleName:null,surname:"Gharoie Ahangar",slug:"reza-gharoie-ahangar",fullName:"Reza Gharoie Ahangar"}],equalEditorOne:{id:"206443",title:"Prof.",name:"Asma",middleName:null,surname:"Salman",slug:"asma-salman",fullName:"Asma Salman",profilePictureURL:"https://mts.intechopen.com/storage/users/206443/images/system/206443.png",biography:"Professor Asma Salman is a blockchain developer and Professor of Finance at the American University in the Emirates, UAE. An Honorary Global Advisor at the Global Academy of Finance and Management, USA, she completed her MBA in Finance and Accounting and earned a Ph.D. in Finance from an AACSB member, AMBA accredited, School of Management at Harbin Institute of Technology, China. Her research credentials include a one-year residency at the Brunel Business School, Brunel University, UK. Prof. Salman also served as the Dubai Cohort supervisor for DBA students under the Nottingham Business School, UK, for seven years and is currently a Ph.D. supervisor at the University of Northampton, UK, where she is a visiting fellow. She also served on the Board of Etihad Airlines during 2019–2020. One of her recent articles on “Bitcoin and Blockchain” gained wide visibility and she is an active speaker on Fintech, blockchain, and crypto events around the GCC. She holds various professional certifications including Chartered Fintech Professional (USA), Certified Financial Manager (USA), Women in Leadership and Management in Higher Education, (UK), and Taxation GCC VAT Compliance, (UK). She recently won an award for “Blockchain Trainer of the Year” from Berkeley Middle East. Other recognitions include the Women Leadership Impact Award by H.E First Lady of Armenia, Research Excellence Award, and the Global Inspirational Women Leadership Award by H.H Sheikh Juma Bin Maktoum Juma Al Maktoum.",institutionString:"American University in the Emirates",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"American University in the Emirates",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8472",title:"Bioactive Compounds in Nutraceutical and Functional Food for Good Human Health",subtitle:null,isOpenForSubmission:!1,hash:"8855452919b8495810ef8e88641feb20",slug:"bioactive-compounds-in-nutraceutical-and-functional-food-for-good-human-health",bookSignature:"Kavita Sharma, Kanchan Mishra, Kula Kamal Senapati and Corina Danciu",coverURL:"https://cdn.intechopen.com/books/images_new/8472.jpg",editors:[{id:"197731",title:"Dr.",name:"Kavita",middleName:null,surname:"Sharma",slug:"kavita-sharma",fullName:"Kavita Sharma"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9959",title:"Biomedical Signal and Image Processing",subtitle:null,isOpenForSubmission:!1,hash:"22b87a09bd6df065d78c175235d367c8",slug:"biomedical-signal-and-image-processing",bookSignature:"Yongxia Zhou",coverURL:"https://cdn.intechopen.com/books/images_new/9959.jpg",editors:[{id:"259308",title:"Dr.",name:"Yongxia",middleName:null,surname:"Zhou",slug:"yongxia-zhou",fullName:"Yongxia Zhou"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9685",title:"Agroecosystems",subtitle:"Very Complex Environmental Systems",isOpenForSubmission:!1,hash:"c44f7b43a9f9610c243dc32300d37df6",slug:"agroecosystems-very-complex-environmental-systems",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/9685.jpg",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8564",title:"Cell Interaction",subtitle:"Molecular and Immunological Basis for Disease Management",isOpenForSubmission:!1,hash:"98d7f080d80524285f091e72a8e92a6d",slug:"cell-interaction-molecular-and-immunological-basis-for-disease-management",bookSignature:"Bhawana Singh",coverURL:"https://cdn.intechopen.com/books/images_new/8564.jpg",editors:[{id:"315192",title:"Dr.",name:"Bhawana",middleName:null,surname:"Singh",slug:"bhawana-singh",fullName:"Bhawana Singh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9515",title:"Update in Geriatrics",subtitle:null,isOpenForSubmission:!1,hash:"913e16c0ae977474b283bbd4269564c8",slug:"update-in-geriatrics",bookSignature:"Somchai Amornyotin",coverURL:"https://cdn.intechopen.com/books/images_new/9515.jpg",editedByType:"Edited by",editors:[{id:"185484",title:"Prof.",name:"Somchai",middleName:null,surname:"Amornyotin",slug:"somchai-amornyotin",fullName:"Somchai Amornyotin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9021",title:"Novel Perspectives of Stem Cell Manufacturing and Therapies",subtitle:null,isOpenForSubmission:!1,hash:"522c6db871783d2a11c17b83f1fd4e18",slug:"novel-perspectives-of-stem-cell-manufacturing-and-therapies",bookSignature:"Diana Kitala and Ana Colette Maurício",coverURL:"https://cdn.intechopen.com/books/images_new/9021.jpg",editedByType:"Edited by",editors:[{id:"203598",title:"Ph.D.",name:"Diana",middleName:null,surname:"Kitala",slug:"diana-kitala",fullName:"Diana Kitala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7030",title:"Satellite Systems",subtitle:"Design, Modeling, Simulation and Analysis",isOpenForSubmission:!1,hash:"b9db6d2645ef248ceb1b33ea75f38e88",slug:"satellite-systems-design-modeling-simulation-and-analysis",bookSignature:"Tien Nguyen",coverURL:"https://cdn.intechopen.com/books/images_new/7030.jpg",editedByType:"Edited by",editors:[{id:"210657",title:"Dr.",name:"Tien M.",middleName:"Manh",surname:"Nguyen",slug:"tien-m.-nguyen",fullName:"Tien M. Nguyen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10413",title:"A Collection of Papers on Chaos Theory and Its Applications",subtitle:null,isOpenForSubmission:!1,hash:"900b71b164948830fec3d6254b7881f7",slug:"a-collection-of-papers-on-chaos-theory-and-its-applications",bookSignature:"Paul Bracken and Dimo I. Uzunov",coverURL:"https://cdn.intechopen.com/books/images_new/10413.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:"9154",title:"Spinal Deformities in Adolescents, Adults and Older Adults",subtitle:null,isOpenForSubmission:!1,hash:"313f1dffa803b60a14ff1e6966e93d91",slug:"spinal-deformities-in-adolescents-adults-and-older-adults",bookSignature:"Josette Bettany-Saltikov and Gokulakannan Kandasamy",coverURL:"https://cdn.intechopen.com/books/images_new/9154.jpg",editedByType:"Edited by",editors:[{id:"94802",title:"Dr.",name:"Josette",middleName:null,surname:"Bettany-Saltikov",slug:"josette-bettany-saltikov",fullName:"Josette Bettany-Saltikov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8148",title:"Investment Strategies in Emerging New Trends in Finance",subtitle:null,isOpenForSubmission:!1,hash:"3b714d96a68d2acdfbd7b50aba6504ca",slug:"investment-strategies-in-emerging-new-trends-in-finance",bookSignature:"Reza Gharoie Ahangar and Asma Salman",coverURL:"https://cdn.intechopen.com/books/images_new/8148.jpg",editedByType:"Edited by",editors:[{id:"91081",title:"Dr.",name:"Reza",middleName:null,surname:"Gharoie Ahangar",slug:"reza-gharoie-ahangar",fullName:"Reza Gharoie Ahangar"}],equalEditorOne:{id:"206443",title:"Prof.",name:"Asma",middleName:null,surname:"Salman",slug:"asma-salman",fullName:"Asma Salman",profilePictureURL:"https://mts.intechopen.com/storage/users/206443/images/system/206443.png",biography:"Professor Asma Salman is a blockchain developer and Professor of Finance at the American University in the Emirates, UAE. An Honorary Global Advisor at the Global Academy of Finance and Management, USA, she completed her MBA in Finance and Accounting and earned a Ph.D. in Finance from an AACSB member, AMBA accredited, School of Management at Harbin Institute of Technology, China. Her research credentials include a one-year residency at the Brunel Business School, Brunel University, UK. Prof. Salman also served as the Dubai Cohort supervisor for DBA students under the Nottingham Business School, UK, for seven years and is currently a Ph.D. supervisor at the University of Northampton, UK, where she is a visiting fellow. She also served on the Board of Etihad Airlines during 2019–2020. One of her recent articles on “Bitcoin and Blockchain” gained wide visibility and she is an active speaker on Fintech, blockchain, and crypto events around the GCC. She holds various professional certifications including Chartered Fintech Professional (USA), Certified Financial Manager (USA), Women in Leadership and Management in Higher Education, (UK), and Taxation GCC VAT Compliance, (UK). She recently won an award for “Blockchain Trainer of the Year” from Berkeley Middle East. Other recognitions include the Women Leadership Impact Award by H.E First Lady of Armenia, Research Excellence Award, and the Global Inspirational Women Leadership Award by H.H Sheikh Juma Bin Maktoum Juma Al Maktoum.",institutionString:"American University in the Emirates",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"American University in the Emirates",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10201",title:"Post-Transition Metals",subtitle:null,isOpenForSubmission:!1,hash:"cc7f53ff5269916e3ce29f65a51a87ae",slug:"post-transition-metals",bookSignature:"Mohammed Muzibur Rahman, Abdullah Mohammed Asiri, Anish Khan, Inamuddin and Thamer Tabbakh",coverURL:"https://cdn.intechopen.com/books/images_new/10201.jpg",editedByType:"Edited by",editors:[{id:"24438",title:"Prof.",name:"Mohammed Muzibur",middleName:null,surname:"Rahman",slug:"mohammed-muzibur-rahman",fullName:"Mohammed Muzibur Rahman"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9959",title:"Biomedical Signal and Image Processing",subtitle:null,isOpenForSubmission:!1,hash:"22b87a09bd6df065d78c175235d367c8",slug:"biomedical-signal-and-image-processing",bookSignature:"Yongxia Zhou",coverURL:"https://cdn.intechopen.com/books/images_new/9959.jpg",editedByType:"Edited by",editors:[{id:"259308",title:"Dr.",name:"Yongxia",middleName:null,surname:"Zhou",slug:"yongxia-zhou",fullName:"Yongxia Zhou"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8472",title:"Bioactive Compounds in Nutraceutical and Functional Food for Good Human Health",subtitle:null,isOpenForSubmission:!1,hash:"8855452919b8495810ef8e88641feb20",slug:"bioactive-compounds-in-nutraceutical-and-functional-food-for-good-human-health",bookSignature:"Kavita Sharma, Kanchan Mishra, Kula Kamal Senapati and Corina Danciu",coverURL:"https://cdn.intechopen.com/books/images_new/8472.jpg",editedByType:"Edited by",editors:[{id:"197731",title:"Dr.",name:"Kavita",middleName:null,surname:"Sharma",slug:"kavita-sharma",fullName:"Kavita Sharma"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8760",title:"Structure Topology and Symplectic Geometry",subtitle:null,isOpenForSubmission:!1,hash:"8974840985ec3652492c83e20233bf02",slug:"structure-topology-and-symplectic-geometry",bookSignature:"Kamal Shah and Min Lei",coverURL:"https://cdn.intechopen.com/books/images_new/8760.jpg",editedByType:"Edited by",editors:[{id:"231748",title:"Dr.",name:"Kamal",middleName:null,surname:"Shah",slug:"kamal-shah",fullName:"Kamal Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"594",title:"Business Management",slug:"business-management",parent:{title:"Numerical Analysis and Scientific Computing",slug:"numerical-analysis-and-scientific-computing"},numberOfBooks:3,numberOfAuthorsAndEditors:155,numberOfWosCitations:96,numberOfCrossrefCitations:60,numberOfDimensionsCitations:119,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"business-management",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"1933",title:"Business Intelligence",subtitle:"Solution for Business Development",isOpenForSubmission:!1,hash:"d72273576047c478fac4567db9e7b649",slug:"business-intelligence-solution-for-business-development",bookSignature:"Marinela Mircea",coverURL:"https://cdn.intechopen.com/books/images_new/1933.jpg",editedByType:"Edited by",editors:[{id:"104617",title:"Prof.",name:"Marinela",middleName:null,surname:"Mircea",slug:"marinela-mircea",fullName:"Marinela Mircea"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"157",title:"Efficient Decision Support Systems",subtitle:"Practice and Challenges From Current to Future",isOpenForSubmission:!1,hash:"bb0fc6d4618f9bceccde50bc6375f025",slug:"efficient-decision-support-systems-practice-and-challenges-from-current-to-future",bookSignature:"Chiang Jao",coverURL:"https://cdn.intechopen.com/books/images_new/157.jpg",editedByType:"Edited by",editors:[{id:"5577",title:"Prof.",name:"Chiang",middleName:null,surname:"Jao",slug:"chiang-jao",fullName:"Chiang Jao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"419",title:"Efficient Decision Support Systems",subtitle:"Practice and Challenges in Multidisciplinary Domains",isOpenForSubmission:!1,hash:null,slug:"efficient-decision-support-systems-practice-and-challenges-in-multidisciplinary-domains",bookSignature:"Chiang Jao",coverURL:"https://cdn.intechopen.com/books/images_new/419.jpg",editedByType:"Edited by",editors:[{id:"5577",title:"Prof.",name:"Chiang",middleName:null,surname:"Jao",slug:"chiang-jao",fullName:"Chiang Jao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:3,mostCitedChapters:[{id:"19351",doi:"10.5772/16897",title:"Decision Support Systems in Water Resources Planning and Management: Stakeholder Participation and the Sustainable Path to Science-Based Decision Making",slug:"decision-support-systems-in-water-resources-planning-and-management-stakeholder-participation-and-th",totalDownloads:2967,totalCrossrefCites:7,totalDimensionsCites:20,book:{slug:"efficient-decision-support-systems-practice-and-challenges-from-current-to-future",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges From Current to Future"},signatures:"Aleix Serrat-Capdevila, Juan B. Valdes and Hoshin V. Gupta",authors:[{id:"26620",title:"Dr.",name:"Aleix",middleName:null,surname:"Serrat-Capdevila",slug:"aleix-serrat-capdevila",fullName:"Aleix Serrat-Capdevila"},{id:"44489",title:"Prof.",name:"Juan",middleName:null,surname:"Valdes",slug:"juan-valdes",fullName:"Juan Valdes"},{id:"44490",title:"Prof.",name:"Hoshin",middleName:null,surname:"Gupta",slug:"hoshin-gupta",fullName:"Hoshin Gupta"}]},{id:"18808",doi:"10.5772/16332",title:"Evaluating the Power Consumption in Carbonate Rock Sawing Process by Using FDAHP and TOPSIS Techniques",slug:"evaluating-the-power-consumption-in-carbonate-rock-sawing-process-by-using-fdahp-and-topsis-techniqu",totalDownloads:1745,totalCrossrefCites:3,totalDimensionsCites:7,book:{slug:"efficient-decision-support-systems-practice-and-challenges-in-multidisciplinary-domains",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges in Multidisciplinary Domains"},signatures:"Reza Mikaeil, Mohammad Ataei and Reza Yousefi",authors:[{id:"24748",title:"Prof.",name:"Reza",middleName:null,surname:"Mikaeil",slug:"reza-mikaeil",fullName:"Reza Mikaeil"},{id:"34217",title:"Prof.",name:"Mohammad",middleName:null,surname:"Ataei",slug:"mohammad-ataei",fullName:"Mohammad Ataei"},{id:"34218",title:"Dr.",name:"Reza",middleName:null,surname:"Yousefi",slug:"reza-yousefi",fullName:"Reza Yousefi"}]},{id:"27300",doi:"10.5772/35477",title:"An Agile Architecture Framework that Leverages the Strengths of Business Intelligence, Decision Management and Service Orientation",slug:"an-agile-architecture-framework-that-leverages-the-strengths-of-business-intelligence-decision-manag",totalDownloads:2338,totalCrossrefCites:4,totalDimensionsCites:7,book:{slug:"business-intelligence-solution-for-business-development",title:"Business Intelligence",fullTitle:"Business Intelligence - Solution for Business Development"},signatures:"Marinela Mircea, Bogdan Ghilic-Micu and Marian Stoica",authors:[{id:"104617",title:"Prof.",name:"Marinela",middleName:null,surname:"Mircea",slug:"marinela-mircea",fullName:"Marinela Mircea"},{id:"116147",title:"Prof.",name:"Marian",middleName:null,surname:"Stoica",slug:"marian-stoica",fullName:"Marian Stoica"},{id:"137166",title:"Prof.",name:"Bogdan",middleName:null,surname:"Ghilic-Micu",slug:"bogdan-ghilic-micu",fullName:"Bogdan Ghilic-Micu"}]}],mostDownloadedChaptersLast30Days:[{id:"27299",title:"Construct an Enterprise Business Intelligence Maturity Model (EBI2M) Using an Integration Approach: A Conceptual Framework",slug:"construct-an-enterprise-business-intelligence-maturity-model-ebi2m-using-an-integration-approach-a-c",totalDownloads:6055,totalCrossrefCites:1,totalDimensionsCites:4,book:{slug:"business-intelligence-solution-for-business-development",title:"Business Intelligence",fullTitle:"Business Intelligence - Solution for Business Development"},signatures:"Min-Hooi Chuah and Kee-Luen Wong",authors:[{id:"104513",title:"Ms.",name:"Min-Hooi",middleName:null,surname:"Chuah",slug:"min-hooi-chuah",fullName:"Min-Hooi Chuah"}]},{id:"19351",title:"Decision Support Systems in Water Resources Planning and Management: Stakeholder Participation and the Sustainable Path to Science-Based Decision Making",slug:"decision-support-systems-in-water-resources-planning-and-management-stakeholder-participation-and-th",totalDownloads:2967,totalCrossrefCites:7,totalDimensionsCites:20,book:{slug:"efficient-decision-support-systems-practice-and-challenges-from-current-to-future",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges From Current to Future"},signatures:"Aleix Serrat-Capdevila, Juan B. Valdes and Hoshin V. Gupta",authors:[{id:"26620",title:"Dr.",name:"Aleix",middleName:null,surname:"Serrat-Capdevila",slug:"aleix-serrat-capdevila",fullName:"Aleix Serrat-Capdevila"},{id:"44489",title:"Prof.",name:"Juan",middleName:null,surname:"Valdes",slug:"juan-valdes",fullName:"Juan Valdes"},{id:"44490",title:"Prof.",name:"Hoshin",middleName:null,surname:"Gupta",slug:"hoshin-gupta",fullName:"Hoshin Gupta"}]},{id:"19346",title:"Decision Support Systems in Agriculture: Administration of Meteorological Data, Use of Geographic Information Systems(GIS) and Validation Methods in Crop Protection Warning Service",slug:"decision-support-systems-in-agriculture-administration-of-meteorological-data-use-of-geographic-info",totalDownloads:2665,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"efficient-decision-support-systems-practice-and-challenges-from-current-to-future",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges From Current to Future"},signatures:"Racca Paolo, Kleinhenz Benno, Zeuner Thorsten, Keil Barbara, Tschöpe Beate and Jung Jeanette",authors:[{id:"40577",title:"Dr.",name:"Paolo",middleName:null,surname:"Racca",slug:"paolo-racca",fullName:"Paolo Racca"},{id:"44077",title:"Dr.",name:"Benno",middleName:null,surname:"Kleinhenz",slug:"benno-kleinhenz",fullName:"Benno Kleinhenz"},{id:"44078",title:"Dr.",name:"Thorsten",middleName:null,surname:"Zeuner",slug:"thorsten-zeuner",fullName:"Thorsten Zeuner"},{id:"44079",title:"Mrs",name:"Barbara",middleName:null,surname:"Keil",slug:"barbara-keil",fullName:"Barbara Keil"},{id:"44080",title:"Mrs",name:"Beate",middleName:null,surname:"Tschöpe",slug:"beate-tschope",fullName:"Beate Tschöpe"},{id:"71145",title:"Mrs.",name:"Jeanette",middleName:null,surname:"Jung",slug:"jeanette-jung",fullName:"Jeanette Jung"}]},{id:"19345",title:"Decision Support Systems in Agriculture: Some Successes and a Bright Future",slug:"decision-support-systems-in-agriculture-some-successes-and-a-bright-future",totalDownloads:3508,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"efficient-decision-support-systems-practice-and-challenges-from-current-to-future",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges From Current to Future"},signatures:"Russell Yost, Tasnee Attanandana, Carol J. Pierce Colfer and Stephen Itoga",authors:[{id:"24894",title:"Prof.",name:"Russell",middleName:null,surname:"Yost",slug:"russell-yost",fullName:"Russell Yost"},{id:"43299",title:"Prof.",name:"Tasnee",middleName:null,surname:"Attanandana",slug:"tasnee-attanandana",fullName:"Tasnee Attanandana"},{id:"71463",title:"Dr.",name:"Carol",middleName:"Jean Pierce",surname:"Colfer",slug:"carol-colfer",fullName:"Carol Colfer"},{id:"71466",title:"Prof.",name:"Stephen",middleName:null,surname:"Itoga",slug:"stephen-itoga",fullName:"Stephen Itoga"}]},{id:"19350",title:"Development of Multi-Componential Decision Support System in Dynamically Changing Application Domain of Environment Protection",slug:"development-of-multi-componential-decision-support-system-in-dynamically-changing-application-domain",totalDownloads:1638,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"efficient-decision-support-systems-practice-and-challenges-from-current-to-future",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges From Current to Future"},signatures:"Dale Dzemydiene and Saulius Maskeliunas",authors:[{id:"37595",title:"Prof.",name:"Dale",middleName:null,surname:"Dzemydiene",slug:"dale-dzemydiene",fullName:"Dale Dzemydiene"},{id:"66795",title:"Dr.",name:"Saulius",middleName:null,surname:"Maskeliunas",slug:"saulius-maskeliunas",fullName:"Saulius Maskeliunas"}]},{id:"18795",title:"Collaboration in Decision Making: A Semi-Automated Support for Managing the Evolution of Virtual Enterprises",slug:"collaboration-in-decision-making-a-semi-automated-support-for-managing-the-evolution-of-virtual-ente",totalDownloads:1655,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"efficient-decision-support-systems-practice-and-challenges-in-multidisciplinary-domains",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges in Multidisciplinary Domains"},signatures:"Marcus Vinicius Drissen-Silva and Ricardo J. Rabelo",authors:[{id:"29600",title:"Dr.",name:"Marcus Vinicius",middleName:null,surname:"Drissen-Silva",slug:"marcus-vinicius-drissen-silva",fullName:"Marcus Vinicius Drissen-Silva"},{id:"35889",title:"Dr.",name:"Ricardo J.",middleName:null,surname:"Rabelo",slug:"ricardo-j.-rabelo",fullName:"Ricardo J. Rabelo"}]},{id:"19338",title:"Identification of Key Drivers of Net Promoter Score Using a Statistical Classification Model",slug:"identification-of-key-drivers-of-net-promoter-score-using-a-statistical-classification-model",totalDownloads:7006,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"efficient-decision-support-systems-practice-and-challenges-from-current-to-future",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges From Current to Future"},signatures:"Daniel R. Jeske, Terrance P. Callanan and Li Guo",authors:[{id:"26781",title:"Dr.",name:"Daniel",middleName:null,surname:"Jeske",slug:"daniel-jeske",fullName:"Daniel Jeske"},{id:"32979",title:"Dr.",name:"Terrance",middleName:"P.",surname:"Callanan",slug:"terrance-callanan",fullName:"Terrance Callanan"},{id:"32980",title:"Ms.",name:"Li",middleName:null,surname:"Guo",slug:"li-guo",fullName:"Li Guo"}]},{id:"18793",title:"Intelligence Decision Support Systems in E-commerce",slug:"intelligence-decision-support-systems-in-e-commerce",totalDownloads:5576,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"efficient-decision-support-systems-practice-and-challenges-in-multidisciplinary-domains",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges in Multidisciplinary Domains"},signatures:"Petr Suchánek, Roman Šperka, Radim Dolák and Martin Miškus",authors:[{id:"29293",title:"Dr.",name:"Petr",middleName:null,surname:"Suchánek",slug:"petr-suchanek",fullName:"Petr Suchánek"},{id:"34194",title:"Mr",name:"Radim",middleName:null,surname:"Dolák",slug:"radim-dolak",fullName:"Radim Dolák"},{id:"34195",title:"MSc",name:"Martin",middleName:null,surname:"Miškus",slug:"martin-miskus",fullName:"Martin Miškus"},{id:"66151",title:"MSc.",name:"Roman",middleName:null,surname:"Šperka",slug:"roman-sperka",fullName:"Roman Šperka"}]},{id:"18797",title:"Linking a Developed Decision Support System with Advanced Methodologies for Optimized Agricultural Water Delivery",slug:"linking-a-developed-decision-support-system-with-advanced-methodologies-for-optimized-agricultural-w",totalDownloads:1636,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"efficient-decision-support-systems-practice-and-challenges-in-multidisciplinary-domains",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges in Multidisciplinary Domains"},signatures:"Kristoph-Dietrich Kinzli, David Gensler and Ramchand Oad",authors:[{id:"26575",title:"Dr.",name:"Kristoph-Dietrich",middleName:null,surname:"Kinzli",slug:"kristoph-dietrich-kinzli",fullName:"Kristoph-Dietrich Kinzli"},{id:"63105",title:"Mr",name:"David",middleName:null,surname:"Gensler",slug:"david-gensler",fullName:"David Gensler"},{id:"74676",title:"Prof.",name:"Ramchand",middleName:null,surname:"Oad",slug:"ramchand-oad",fullName:"Ramchand Oad"}]},{id:"18800",title:"Providing Efficient Decision Support for Green Operations Management: An Integrated Perspective",slug:"providing-efficient-decision-support-for-green-operations-management-an-integrated-perspective",totalDownloads:3032,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"efficient-decision-support-systems-practice-and-challenges-in-multidisciplinary-domains",title:"Efficient Decision Support Systems",fullTitle:"Efficient Decision Support Systems - Practice and Challenges in Multidisciplinary Domains"},signatures:"Shaofeng Liu and Meili Jiang",authors:[{id:"6479",title:"Dr.",name:"Shaofeng",middleName:null,surname:"Liu",slug:"shaofeng-liu",fullName:"Shaofeng Liu"},{id:"26116",title:"Mrs.",name:"Meili",middleName:null,surname:"Jiang",slug:"meili-jiang",fullName:"Meili Jiang"}]}],onlineFirstChaptersFilter:{topicSlug:"business-management",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},route:{name:"chapter.detail",path:"/books/antibody-engineering/use-applications-and-mechanisms-of-intracellular-actions-of-camelid-vhhs",hash:"",query:{},params:{book:"antibody-engineering",chapter:"use-applications-and-mechanisms-of-intracellular-actions-of-camelid-vhhs"},fullPath:"/books/antibody-engineering/use-applications-and-mechanisms-of-intracellular-actions-of-camelid-vhhs",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)}()