\\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!
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 179 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 252 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!
\n'}],latestNews:[{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"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"},{slug:"intechopen-s-chapter-awarded-the-guenther-von-pannewitz-preis-2020-20200715",title:"IntechOpen's Chapter Awarded the Günther-von-Pannewitz-Preis 2020"}]},book:{item:{type:"book",id:"588",leadTitle:null,fullTitle:"Ceramic Coatings - Applications in Engineering",title:"Ceramic Coatings",subtitle:"Applications in Engineering",reviewType:"peer-reviewed",abstract:"The main target of this book is to state the latest advancement in ceramic coatings technology in various industrial fields. The book includes topics related to the applications of ceramic coating covers in enginnering, including fabrication route (electrophoretic deposition and physical deposition) and applications in turbine parts, internal combustion engine, pigment, foundry, etc.",isbn:null,printIsbn:"978-953-51-0083-6",pdfIsbn:"978-953-51-6124-0",doi:"10.5772/1101",price:119,priceEur:129,priceUsd:155,slug:"ceramic-coatings-applications-in-engineering",numberOfPages:298,isOpenForSubmission:!1,isInWos:1,hash:"87d35270dc765ca2c5fa7fd7063c7f60",bookSignature:"Feng Shi",publishedDate:"February 24th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/588.jpg",numberOfDownloads:42883,numberOfWosCitations:33,numberOfCrossrefCitations:28,numberOfDimensionsCitations:42,hasAltmetrics:1,numberOfTotalCitations:103,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 1st 2011",dateEndSecondStepPublish:"March 29th 2011",dateEndThirdStepPublish:"August 3rd 2011",dateEndFourthStepPublish:"September 2nd 2011",dateEndFifthStepPublish:"December 31st 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"24821",title:"Dr.",name:"Feng",middleName:null,surname:"Shi",slug:"feng-shi",fullName:"Feng Shi",profilePictureURL:"https://mts.intechopen.com/storage/users/24821/images/2367_n.jpg",biography:"Feng Shi, PH.D, majored in Solid State Electronics and graduated in 09/2003 from Tianjin University, P. R. China; Professor in School of Materials Science and Technology, Shandong University of Science and Technology. Now, I study the lattice dynamics of electronic ceramics, and fabrication/properties of semiconductor nanomaterials. I have published more than 140 papers and more than 120 papers were indexed in SCI or EI.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Tianjin University",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"924",title:"Surface Engineering",slug:"ceramics-surface-engineering"}],chapters:[{id:"29750",title:"Ti-O Film Cathodically-Electrodeposited on the Surface of TiNi SMA and Its Bioactivity and Blood Compatibility",doi:"10.5772/31460",slug:"ti-o-film-cathodically-electrodeposited-on-the-surface-of-tini-sma-and-its-bioactivity-and-blood-com",totalDownloads:2189,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Zhu Weidong",downloadPdfUrl:"/chapter/pdf-download/29750",previewPdfUrl:"/chapter/pdf-preview/29750",authors:[{id:"87260",title:"Prof.",name:"Zhu",surname:"Weidong",slug:"zhu-weidong",fullName:"Zhu Weidong"}],corrections:null},{id:"29751",title:"Ceramic Coatings Obtained by Electrophoretic Deposition: Fundamentals, Models, Post-Deposition Processes and Applications",doi:"10.5772/29435",slug:"ceramic-coatings-obtained-by-electrophoretic-deposition",totalDownloads:4855,totalCrossrefCites:6,totalDimensionsCites:12,signatures:"M. Federica De Riccardis",downloadPdfUrl:"/chapter/pdf-download/29751",previewPdfUrl:"/chapter/pdf-preview/29751",authors:[{id:"77857",title:"Dr.",name:"M. Federica",surname:"De Riccardis",slug:"m.-federica-de-riccardis",fullName:"M. Federica De Riccardis"}],corrections:null},{id:"29752",title:"Magnetron Sputtered BG Thin Films: An Alternative Biofunctionalization Approach – Peculiarities of Bioglass Sputtering and Bioactivity Behaviour",doi:"10.5772/30244",slug:"magnetron-sputtered-bg-thin-films-an-alternative-biofunctionalization-approach-peculiarities-of-biog",totalDownloads:2193,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"George E. Stan and José M.F. Ferreira",downloadPdfUrl:"/chapter/pdf-download/29752",previewPdfUrl:"/chapter/pdf-preview/29752",authors:[{id:"34618",title:"Prof.",name:"José",surname:"Fonte Ferreira",slug:"jose-fonte-ferreira",fullName:"José Fonte Ferreira"},{id:"81572",title:"Dr.",name:"George",surname:"Stan",slug:"george-stan",fullName:"George Stan"}],corrections:null},{id:"29753",title:"Erosion Behavior of Plasma Sprayed Alumina and Calcia-Stabilized Zirconia Coatings on Cast Iron Substrate",doi:"10.5772/30912",slug:"erosion-wear-behaviour-of-plasma-sprayed-alumina-and-calcia-stabilized-zirconia-coatings-on-cast-iro",totalDownloads:3115,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"N. Krishnamurthy, M.S. Murali, B. Venkataraman and P.G. Mukunda",downloadPdfUrl:"/chapter/pdf-download/29753",previewPdfUrl:"/chapter/pdf-preview/29753",authors:[{id:"84732",title:"Dr.",name:"Narayanappa",surname:"Krishnamurthy",slug:"narayanappa-krishnamurthy",fullName:"Narayanappa Krishnamurthy"}],corrections:null},{id:"29754",title:"Investigations of Thermal Barrier Coatings for Turbine Parts",doi:"10.5772/31354",slug:"investigations-of-thermal-barrier-coatings-for-turbine-parts",totalDownloads:6756,totalCrossrefCites:3,totalDimensionsCites:4,signatures:"Alexandr Lepeshkin",downloadPdfUrl:"/chapter/pdf-download/29754",previewPdfUrl:"/chapter/pdf-preview/29754",authors:[{id:"86719",title:"Dr.",name:"Alexandr",surname:"Lepeshkin",slug:"alexandr-lepeshkin",fullName:"Alexandr Lepeshkin"}],corrections:null},{id:"29755",title:"Thermal Spraying of Oxide Ceramic and Ceramic Metallic Coatings",doi:"10.5772/29739",slug:"thermal-spraying-of-oxide-ceramic-and-ceramic-metallic-coatings",totalDownloads:6456,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Martin Erne and Daniel Kolar",downloadPdfUrl:"/chapter/pdf-download/29755",previewPdfUrl:"/chapter/pdf-preview/29755",authors:[{id:"79126",title:"Mr.",name:"Martin",surname:"Erne",slug:"martin-erne",fullName:"Martin Erne"},{id:"132452",title:"Mr.",name:"Daniel",surname:"Kolar",slug:"daniel-kolar",fullName:"Daniel Kolar"}],corrections:null},{id:"29756",title:"Ceramic Coating Applications and Research Fields for Internal Combustion Engines",doi:"10.5772/29993",slug:"ceramic-coating-applications-and-research-fields-for-internal-combustion-engines",totalDownloads:6719,totalCrossrefCites:12,totalDimensionsCites:15,signatures:"Murat Ciniviz, Mustafa Sahir Salman, Eyüb Canlı, Hüseyin Köse and Özgür Solmaz",downloadPdfUrl:"/chapter/pdf-download/29756",previewPdfUrl:"/chapter/pdf-preview/29756",authors:[{id:"80282",title:"Dr.",name:"Murat",surname:"Ciniviz",slug:"murat-ciniviz",fullName:"Murat Ciniviz"},{id:"86782",title:"MSc.",name:"Eyüb",surname:"Canlı",slug:"eyub-canli",fullName:"Eyüb Canlı"},{id:"95463",title:"MSc.",name:"Hüseyin",surname:"Köse",slug:"huseyin-kose",fullName:"Hüseyin Köse"},{id:"95464",title:"MSc.",name:"Özgür",surname:"Solmaz",slug:"ozgur-solmaz",fullName:"Özgür Solmaz"},{id:"136904",title:"Prof.",name:"Mustafa Sahir",surname:"Salman",slug:"mustafa-sahir-salman",fullName:"Mustafa Sahir Salman"}],corrections:null},{id:"29757",title:"Ceramic Coatings for Pigments",doi:"10.5772/30010",slug:"ceramic-coatings-for-pigments",totalDownloads:4232,totalCrossrefCites:6,totalDimensionsCites:6,signatures:"A.R. Mirhabibi",downloadPdfUrl:"/chapter/pdf-download/29757",previewPdfUrl:"/chapter/pdf-preview/29757",authors:[{id:"80383",title:"Prof.",name:"Ali Reza",surname:"Mirhabibi",slug:"ali-reza-mirhabibi",fullName:"Ali Reza Mirhabibi"}],corrections:null},{id:"29758",title:"Ceramic Coating for Cast House Application",doi:"10.5772/31273",slug:"ceramic-coatings-for-application-in-foundry",totalDownloads:6371,totalCrossrefCites:1,totalDimensionsCites:2,signatures:"Zagorka Aćimović-Pavlović, Aurel Prstić, Ljubiša Andrić, Vladan Milošević and Sonja Milićević",downloadPdfUrl:"/chapter/pdf-download/29758",previewPdfUrl:"/chapter/pdf-preview/29758",authors:[{id:"86328",title:"MSc.",name:"Sonja",surname:"Milicevic",slug:"sonja-milicevic",fullName:"Sonja Milicevic"},{id:"86345",title:"Prof.",name:"Zagorka",surname:"Aćimović Pavlović",slug:"zagorka-acimovic-pavlovic",fullName:"Zagorka Aćimović Pavlović"},{id:"86347",title:"Prof.",name:"Ljubiša",surname:"Andrić",slug:"ljubisa-andric",fullName:"Ljubiša Andrić"},{id:"86348",title:"Dr.",name:"Vladan",surname:"Milošević",slug:"vladan-milosevic",fullName:"Vladan Milošević"},{id:"86351",title:"MSc.",name:"Aurel",surname:"Prstic",slug:"aurel-prstic",fullName:"Aurel Prstic"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"2200",title:"Ceramic Materials",subtitle:"Progress in Modern Ceramics",isOpenForSubmission:!1,hash:"612da9cb87615f384b89b64be02c39be",slug:"ceramic-materials-progress-in-modern-ceramics",bookSignature:"Feng Shi",coverURL:"https://cdn.intechopen.com/books/images_new/2200.jpg",editedByType:"Edited by",editors:[{id:"24821",title:"Dr.",name:"Feng",surname:"Shi",slug:"feng-shi",fullName:"Feng Shi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5827",title:"New Technologies in Protective Coatings",subtitle:null,isOpenForSubmission:!1,hash:"b569584985468cd3d20b12d8098a3a9c",slug:"new-technologies-in-protective-coatings",bookSignature:"Carlos Giudice and Guadalupe Canosa",coverURL:"https://cdn.intechopen.com/books/images_new/5827.jpg",editedByType:"Edited by",editors:[{id:"100127",title:"Dr.",name:"Carlos",surname:"Giudice",slug:"carlos-giudice",fullName:"Carlos Giudice"}],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:"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:"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:"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:"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"}},{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:"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:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"72181",slug:"corrigendum-to-potassium-channels-as-a-potential-target-spot-for-drugs",title:"Corrigendum to: Potassium Channels as a Potential Target Spot for Drugs",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/72181.pdf",downloadPdfUrl:"/chapter/pdf-download/72181",previewPdfUrl:"/chapter/pdf-preview/72181",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/72181",risUrl:"/chapter/ris/72181",chapter:{id:"71907",slug:"potassium-channels-as-a-potential-target-spot-for-drugs",signatures:"Vladimir Djokic and Radmila Novakovic",dateSubmitted:"October 13th 2019",dateReviewed:"March 18th 2020",datePrePublished:"April 28th 2020",datePublished:"December 16th 2020",book:{id:"10143",title:"Molecular Pharmacology",subtitle:null,fullTitle:"Molecular Pharmacology",slug:"molecular-pharmacology",publishedDate:"December 16th 2020",bookSignature:"Angel Catala and Usama Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/10143.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"313382",title:"Ph.D.",name:"Radmila",middleName:null,surname:"Novakovic",fullName:"Radmila Novakovic",slug:"radmila-novakovic",email:"radmila.novakovic@med.bg.ac.rs",position:null,institution:null}]}},chapter:{id:"71907",slug:"potassium-channels-as-a-potential-target-spot-for-drugs",signatures:"Vladimir Djokic and Radmila Novakovic",dateSubmitted:"October 13th 2019",dateReviewed:"March 18th 2020",datePrePublished:"April 28th 2020",datePublished:"December 16th 2020",book:{id:"10143",title:"Molecular Pharmacology",subtitle:null,fullTitle:"Molecular Pharmacology",slug:"molecular-pharmacology",publishedDate:"December 16th 2020",bookSignature:"Angel Catala and Usama Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/10143.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"313382",title:"Ph.D.",name:"Radmila",middleName:null,surname:"Novakovic",fullName:"Radmila Novakovic",slug:"radmila-novakovic",email:"radmila.novakovic@med.bg.ac.rs",position:null,institution:null}]},book:{id:"10143",title:"Molecular Pharmacology",subtitle:null,fullTitle:"Molecular Pharmacology",slug:"molecular-pharmacology",publishedDate:"December 16th 2020",bookSignature:"Angel Catala and Usama Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/10143.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"8696",leadTitle:null,title:"Pulmonary Insufficiency",subtitle:null,reviewType:"peer-reviewed",abstract:"This book will be a self-contained collection of scholarly papers targeting an audience of practicing researchers, academics, PhD students and other scientists. The contents of the book will be written by multiple authors and edited by experts in the field.",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"0dfed0b2495fdf08ebf2f5779db08135",bookSignature:"",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8696.jpg",keywords:null,numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 10th 2018",dateEndSecondStepPublish:"July 31st 2018",dateEndThirdStepPublish:"September 29th 2018",dateEndFourthStepPublish:"December 18th 2018",dateEndFifthStepPublish:"February 16th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:1,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"René Mauricio",surname:"Barría",slug:"rene-mauricio-barria",fullName:"René Mauricio Barría"}],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:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"35182",title:"Measuring Technological Change - Concept, Methods, and Implications",doi:"10.5772/36251",slug:"measuring-technological-change-concept-methods-and-implications",body:null,keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/35182.pdf",chapterXML:null,downloadPdfUrl:"/chapter/pdf-download/35182",previewPdfUrl:"/chapter/pdf-preview/35182",totalDownloads:2998,totalViews:726,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,dateSubmitted:"May 20th 2011",dateReviewed:"February 14th 2012",datePrePublished:null,datePublished:"April 11th 2012",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/35182",risUrl:"/chapter/ris/35182",book:{slug:"technological-change"},signatures:"Byoung Soo Kim",authors:[{id:"107645",title:"Mr.",name:"Byoung Soo",middleName:null,surname:"Kim",fullName:"Byoung Soo Kim",slug:"byoung-soo-kim",email:"deeple@snu.ac.kr",position:null,institution:{name:"Korea Institute of Science and Technology",institutionURL:null,country:{name:"Korea, South"}}}],sections:null,chapterReferences:null,footnotes:null,contributors:null,corrections:null},book:{id:"1892",title:"Technological Change",subtitle:null,fullTitle:"Technological Change",slug:"technological-change",publishedDate:"April 11th 2012",bookSignature:"Aurora A.C. Teixeira",coverURL:"https://cdn.intechopen.com/books/images_new/1892.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"112335",title:"Dr.",name:"Aurora",middleName:"A.C.",surname:"Teixeira",slug:"aurora-teixeira",fullName:"Aurora Teixeira"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"35178",title:"Technological Change and Economic Transformation",slug:"technological-change-and-economic-transformation",totalDownloads:6699,totalCrossrefCites:0,signatures:"Musa Jega Ibrahim",authors:[{id:"107299",title:"Dr.",name:"Musa Jega",middleName:null,surname:"Ibrahim",fullName:"Musa Jega Ibrahim",slug:"musa-jega-ibrahim"}]},{id:"35179",title:"The Social Consequences of Technological Change in Capitalist Societies",slug:"social-implications-of-technological-change-some-marxian-themes",totalDownloads:3341,totalCrossrefCites:0,signatures:"Tony Smith",authors:[{id:"110595",title:"Prof.",name:"Tony",middleName:null,surname:"Smith",fullName:"Tony Smith",slug:"tony-smith"}]},{id:"35180",title:"Intellectual Property Rights and Endogenous Economic Growth – Uncovering the Main Gaps in the Research Agenda",slug:"-intellectual-property-rights-technological-change-and-economic-growth-uncovering-the-main-gaps-in-t",totalDownloads:2002,totalCrossrefCites:0,signatures:"Monica L. Azevedo, Sandra T. Silva and Oscar Afonso",authors:[{id:"107797",title:"Prof.",name:"Oscar",middleName:null,surname:"Afonso",fullName:"Oscar Afonso",slug:"oscar-afonso"},{id:"114248",title:"Prof.",name:"Sandra",middleName:"T.",surname:"Silva",fullName:"Sandra Silva",slug:"sandra-silva"},{id:"116054",title:"Ph.D. Student",name:"Mónica",middleName:null,surname:"Azevedo",fullName:"Mónica Azevedo",slug:"monica-azevedo"}]},{id:"35181",title:"Reconciling Orthodox and Heterodox Approaches to Economic Growth – A Modeling Proposal",slug:"reconciling-orthodox-and-heterodox-approaches-to-economic-growth-a-modeling-proposal",totalDownloads:1400,totalCrossrefCites:0,signatures:"Aurora A.C. Teixeira",authors:[{id:"112335",title:"Dr.",name:"Aurora",middleName:"A.C.",surname:"Teixeira",fullName:"Aurora Teixeira",slug:"aurora-teixeira"}]},{id:"35182",title:"Measuring Technological Change - Concept, Methods, and Implications",slug:"measuring-technological-change-concept-methods-and-implications",totalDownloads:2998,totalCrossrefCites:0,signatures:"Byoung Soo Kim",authors:[{id:"107645",title:"Mr.",name:"Byoung Soo",middleName:null,surname:"Kim",fullName:"Byoung Soo Kim",slug:"byoung-soo-kim"}]},{id:"35183",title:"Quantitative Technology Forecasting Techniques",slug:"quantitative-technology-forecasting-techniques",totalDownloads:11716,totalCrossrefCites:1,signatures:"Steven R. Walk",authors:[{id:"115236",title:"Prof.",name:"Steven",middleName:"Robert",surname:"Walk",fullName:"Steven Walk",slug:"steven-walk"}]},{id:"35184",title:"Trade, SBTC and Skill Premia – A Cross-Country and Cross-Gender Analysis",slug:"trade-sbtc-and-skill-premia-a-cross-country-and-cross-gender-analysis",totalDownloads:1358,totalCrossrefCites:0,signatures:"Oscar Afonso, Alexandre Almeida and Cristina Santos",authors:[{id:"107797",title:"Prof.",name:"Oscar",middleName:null,surname:"Afonso",fullName:"Oscar Afonso",slug:"oscar-afonso"}]},{id:"35185",title:"Internationalization Approaches of the Automotive Innovation System - A Historical Perspective",slug:"internationalization-approaches-of-the-automotive-innovation-system-a-historical-perspective",totalDownloads:2436,totalCrossrefCites:0,signatures:"António C. Moreira and Ana Carolina Carvalho",authors:[{id:"109428",title:"Dr.",name:"António Carrizo",middleName:null,surname:"Moreira",fullName:"António Carrizo Moreira",slug:"antonio-carrizo-moreira"},{id:"114427",title:"MSc.",name:"Ana Carolina",middleName:null,surname:"Carvalho",fullName:"Ana Carolina Carvalho",slug:"ana-carolina-carvalho"}]},{id:"35186",title:"Towards the European Union - Impact of FDI and Technological Change on Turkish Banking",slug:"towards-the-european-union-impact-of-fdi-and-technological-change-in-turkish-banking",totalDownloads:1361,totalCrossrefCites:0,signatures:"Özlem Olgu",authors:[{id:"108683",title:"Dr.",name:"Ozlem",middleName:null,surname:"Olgu",fullName:"Ozlem Olgu",slug:"ozlem-olgu"}]},{id:"35187",title:"The Impact of ICTs on Innovative Sustainable Development in East and Southern Africa",slug:"impact-of-icts-on-innovative-sustainable-development-in-east-and-southern-africa",totalDownloads:1877,totalCrossrefCites:0,signatures:"Gabriel Kabanda",authors:[{id:"108346",title:"Prof.",name:"Gabriel",middleName:null,surname:"Kabanda",fullName:"Gabriel Kabanda",slug:"gabriel-kabanda"}]},{id:"35188",title:"Knowledge Frontiers for Sustainable Growth and Development in Zimbabwe",slug:"knowledge-frontiers-for-sustainable-growth-and-development-in-zimbabwe-",totalDownloads:2548,totalCrossrefCites:0,signatures:"Gabriel Kabanda",authors:[{id:"108346",title:"Prof.",name:"Gabriel",middleName:null,surname:"Kabanda",fullName:"Gabriel Kabanda",slug:"gabriel-kabanda"}]}]},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"36273",title:"Introduction to Infrared Spectroscopy",slug:"introduction-to-infrared-spectroscopy",signatures:"Theophile Theophanides",authors:[{id:"37194",title:"Dr.",name:"Theophanides",middleName:null,surname:"Theophile",fullName:"Theophanides Theophile",slug:"theophanides-theophile"}]},{id:"36166",title:"Using Infrared Spectroscopy to Identify New Amorphous Phases - A Case Study of Carbonato Complex Formed by Mechanochemical Processing",slug:"using-infrared-spectroscopy-to-identify-new-amorphous-phases-a-case-study-of-carbonato-complexes-fo",signatures:"Tadej Rojac, Primož Šegedin and Marija Kosec",authors:[{id:"25116",title:"Prof.",name:"Marija",middleName:null,surname:"Kosec",fullName:"Marija Kosec",slug:"marija-kosec"},{id:"105876",title:"Dr.",name:"Tadej",middleName:null,surname:"Rojac",fullName:"Tadej Rojac",slug:"tadej-rojac"},{id:"111754",title:"Prof.",name:"Primoz",middleName:null,surname:"Segedin",fullName:"Primoz Segedin",slug:"primoz-segedin"}]},{id:"36167",title:"Application of Infrared Spectroscopy to Analysis of Chitosan/Clay Nanocomposites",slug:"application-of-infrared-spectroscopy-to-analysis-of-chitosan-clay-nanocomposites",signatures:"Suédina M.L. Silva, Carla R.C. Braga, Marcus V.L. Fook, Claudia M.O. Raposo, Laura H. Carvalho and Eduardo L. Canedo",authors:[{id:"104808",title:"Prof.",name:"Suedina Maria",middleName:"De Lima",surname:"Silva",fullName:"Suedina Maria Silva",slug:"suedina-maria-silva"},{id:"111910",title:"Prof.",name:"Carla",middleName:"Lima",surname:"R. C. Braga",fullName:"Carla R. C. Braga",slug:"carla-r.-c.-braga"},{id:"142933",title:"Prof.",name:"Marcus Vinícius",middleName:null,surname:"Lia Fook",fullName:"Marcus Vinícius Lia Fook",slug:"marcus-vinicius-lia-fook"},{id:"142934",title:"Prof.",name:"Claudia Maria",middleName:null,surname:"De Oliveira Raposo",fullName:"Claudia Maria De Oliveira Raposo",slug:"claudia-maria-de-oliveira-raposo"},{id:"142936",title:"Prof.",name:"Laura",middleName:null,surname:"Hecker De Carvalho",fullName:"Laura Hecker De Carvalho",slug:"laura-hecker-de-carvalho"},{id:"142939",title:"Dr.",name:"Eduardo Luis",middleName:null,surname:"Canedo",fullName:"Eduardo Luis Canedo",slug:"eduardo-luis-canedo"}]},{id:"36168",title:"Structural and Optical Behavior of Vanadate-Tellurate Glasses Containing PbO or Sm2O3",slug:"structural-and-optical-behavior-of-vanadate-tellurate-glasses",signatures:"E. Culea, S. Rada, M. Culea and M. Rada",authors:[{id:"114650",title:"Dr",name:"Eugen",middleName:null,surname:"Culea",fullName:"Eugen Culea",slug:"eugen-culea"},{id:"114653",title:"Dr.",name:"Simona",middleName:null,surname:"Rada",fullName:"Simona Rada",slug:"simona-rada"}]},{id:"36169",title:"Water in Rocks and Minerals - Species, Distributions, and Temperature Dependences",slug:"water-in-rocks-and-minerals-species-distributions-and-temperature-dependences",signatures:"Jun-ichi Fukuda",authors:[{id:"105384",title:"Dr.",name:"Jun-Ichi",middleName:null,surname:"Fukuda",fullName:"Jun-Ichi Fukuda",slug:"jun-ichi-fukuda"}]},{id:"36170",title:"Attenuated Total Reflection - Infrared Spectroscopy Applied to the Study of Mineral - Aqueous Electrolyte Solution Interfaces: A General Overview and a Case Study",slug:"attenuated-total-reflection-infrared-spectroscopy-applied-to-the-study-of-mineral-aqueous-el",signatures:"Grégory Lefèvre, Tajana Preočanin and Johannes Lützenkirchen",authors:[{id:"108416",title:"Dr.",name:"Johannes",middleName:null,surname:"Lützenkirchen",fullName:"Johannes Lützenkirchen",slug:"johannes-lutzenkirchen"},{id:"111675",title:"Dr.",name:"Gregory",middleName:null,surname:"Lefevre",fullName:"Gregory Lefevre",slug:"gregory-lefevre"},{id:"111676",title:"Prof.",name:"Tajana",middleName:null,surname:"Preocanin",fullName:"Tajana Preocanin",slug:"tajana-preocanin"}]},{id:"36171",title:"Research of Calcium Phosphates Using Fourier Transform Infrared Spectroscopy",slug:"research-of-calcium-phosphates-using-fourier-transformation-infrared-spectroscopy",signatures:"Liga Berzina-Cimdina and Natalija Borodajenko",authors:[{id:"110522",title:"Prof.",name:"Liga",middleName:null,surname:"Berzina-Cimdina",fullName:"Liga Berzina-Cimdina",slug:"liga-berzina-cimdina"},{id:"112181",title:"MSc.",name:"Natalija",middleName:null,surname:"Borodajenko",fullName:"Natalija Borodajenko",slug:"natalija-borodajenko"}]},{id:"36172",title:"FTIR Spectroscopy of Adsorbed Probe Molecules for Analyzing the Surface Properties of Supported Pt (Pd) Catalysts",slug:"ftir-spectroscopy-of-adsorbed-probe-molecules-for-analyzing-the-surface-properties-of-supported-pt-p",signatures:"Olga B. Belskaya, Irina G. Danilova, Maxim O. Kazakov, Roman M. Mironenko, Alexander V. Lavrenov and Vladimir A. Likholobov",authors:[{id:"107715",title:"Dr.",name:"Olga",middleName:null,surname:"Belskaya",fullName:"Olga Belskaya",slug:"olga-belskaya"},{id:"140198",title:"Dr.",name:"Irina",middleName:null,surname:"Danilova",fullName:"Irina Danilova",slug:"irina-danilova"},{id:"140200",title:"Dr.",name:"Maxim",middleName:null,surname:"Kazakov",fullName:"Maxim Kazakov",slug:"maxim-kazakov"},{id:"140202",title:"Mr.",name:"Roman",middleName:"Mikhailovich",surname:"Mironenko",fullName:"Roman Mironenko",slug:"roman-mironenko"},{id:"140203",title:"Dr.",name:"Alexander",middleName:null,surname:"Lavrenov",fullName:"Alexander Lavrenov",slug:"alexander-lavrenov"},{id:"140204",title:"Prof.",name:"Vladimir",middleName:null,surname:"Likholobov",fullName:"Vladimir Likholobov",slug:"vladimir-likholobov"}]},{id:"36173",title:"Hydrothermal Treatment of Hokkaido Peat - An Application of FTIR and 13C NMR Spectroscopy on Examining of Artificial Coalification Process and Development",slug:"hydrothermal-treatment-of-hokkaido-peat-an-application-of-ftir-and-13c-nmr-spectroscopy-on-examinin",signatures:"Anggoro Tri Mursito and Tsuyoshi Hirajima",authors:[{id:"104786",title:"Dr.",name:"Anggoro Tri",middleName:null,surname:"Mursito",fullName:"Anggoro Tri Mursito",slug:"anggoro-tri-mursito"},{id:"110978",title:"Prof.",name:"Tsuyoshi",middleName:null,surname:"Hirajima",fullName:"Tsuyoshi Hirajima",slug:"tsuyoshi-hirajima"}]},{id:"36174",title:"FTIR - An Essential Characterization Technique for Polymeric Materials",slug:"ftir-an-essential-characterization-technique-for-polymeric-materials",signatures:"Vladimir A. Escobar Barrios, José R. Rangel Méndez, Nancy V. Pérez Aguilar, Guillermo Andrade Espinosa and José L. Dávila Rodríguez",authors:[{id:"12709",title:"Dr.",name:"Jose Rene",middleName:null,surname:"Rangel-Mendez",fullName:"Jose Rene Rangel-Mendez",slug:"jose-rene-rangel-mendez"},{id:"12711",title:"Dr.",name:"Vladimir Alonso",middleName:null,surname:"Escobar Barrios",fullName:"Vladimir Alonso Escobar Barrios",slug:"vladimir-alonso-escobar-barrios"},{id:"112164",title:"Dr",name:"Guillermo",middleName:null,surname:"Andrade-Espinosa",fullName:"Guillermo Andrade-Espinosa",slug:"guillermo-andrade-espinosa"},{id:"112165",title:"Dr.",name:"José Luis",middleName:null,surname:"Dávila-Rodríguez",fullName:"José Luis Dávila-Rodríguez",slug:"jose-luis-davila-rodriguez"},{id:"112167",title:"Dr.",name:"Nancy Verónica",middleName:null,surname:"Pérez-Aguilar",fullName:"Nancy Verónica Pérez-Aguilar",slug:"nancy-veronica-perez-aguilar"}]},{id:"36175",title:"Preparation and Characterization of PVDF/PMMA/Graphene Polymer Blend Nanocomposites by Using ATR-FTIR Technique",slug:"preparation-and-characterization-of-pvdf-pmma-graphene-polymer-blend-nanocomposites-by-using-ft-ir-t",signatures:"Somayeh Mohamadi",authors:[{id:"108556",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohamadi",fullName:"Somayeh Mohamadi",slug:"somayeh-mohamadi"}]},{id:"36176",title:"Reflectance IR Spectroscopy",slug:"fundamental-of-reflectance-ir-spectroscopy",signatures:"Zahra Monsef Khoshhesab",authors:[{id:"111629",title:"Dr.",name:"Zahra",middleName:null,surname:"Monsef Khoshhesab",fullName:"Zahra Monsef Khoshhesab",slug:"zahra-monsef-khoshhesab"}]},{id:"36177",title:"Evaluation of Graft Copolymerization of Acrylic Monomers Onto Natural Polymers by Means Infrared Spectroscopy",slug:"evaluation-of-graft-copolymerization-of-acrylic-monomers-onto-natural-polymers-by-means-infrared-spe",signatures:"José Luis Rivera-Armenta, Cynthia Graciela Flores-Hernández, Ruth Zurisadai Del Angel-Aldana, Ana María Mendoza-Martínez, Carlos Velasco-Santos and Ana Laura Martínez-Hernández",authors:[{id:"37761",title:"Prof.",name:"Ana Laura",middleName:null,surname:"Martinez-Hernandez",fullName:"Ana Laura Martinez-Hernandez",slug:"ana-laura-martinez-hernandez"},{id:"107855",title:"Dr.",name:"Jose Luis",middleName:null,surname:"Rivera Armenta",fullName:"Jose Luis Rivera Armenta",slug:"jose-luis-rivera-armenta"},{id:"108894",title:"MSc.",name:"Cynthia Graciela",middleName:null,surname:"Flores-Hernández",fullName:"Cynthia Graciela Flores-Hernández",slug:"cynthia-graciela-flores-hernandez"},{id:"108896",title:"MSc.",name:"Ruth Zurisadai",middleName:null,surname:"Del Angel Aldana",fullName:"Ruth Zurisadai Del Angel Aldana",slug:"ruth-zurisadai-del-angel-aldana"},{id:"108898",title:"Dr.",name:"Carlos",middleName:null,surname:"Velasco-Santos",fullName:"Carlos Velasco-Santos",slug:"carlos-velasco-santos"},{id:"108905",title:"Dr.",name:"Ana Maria",middleName:null,surname:"Mendoza-Martínez",fullName:"Ana Maria Mendoza-Martínez",slug:"ana-maria-mendoza-martinez"}]},{id:"36178",title:"Applications of FTIR on Epoxy Resins - Identification, Monitoring the Curing Process, Phase Separation and Water Uptake",slug:"applications-of-ftir-on-epoxy-resins-identification-monitoring-the-curing-process-phase-separatio",signatures:"María González González, Juan Carlos Cabanelas and Juan Baselga",authors:[{id:"107857",title:"Prof.",name:"Juan",middleName:null,surname:"Baselga",fullName:"Juan Baselga",slug:"juan-baselga"},{id:"138113",title:"Dr.",name:"María",middleName:null,surname:"González",fullName:"María González",slug:"maria-gonzalez"},{id:"138114",title:"Dr.",name:"Juan C.",middleName:null,surname:"Cabanelas",fullName:"Juan C. Cabanelas",slug:"juan-c.-cabanelas"}]},{id:"36179",title:"Use of FTIR Analysis to Control the Self-Healing Functionality of Epoxy Resins",slug:"use-of-ft-ir-analysis-to-control-the-self-healing-functionality-of-epoxy-resins",signatures:"Liberata Guadagno and Marialuigia Raimondo",authors:[{id:"106836",title:"Prof.",name:"Liberata",middleName:null,surname:"Guadagno",fullName:"Liberata Guadagno",slug:"liberata-guadagno"}]},{id:"36180",title:"Infrared Analysis of Electrostatic Layer-By-Layer Polymer Membranes Having Characteristics of Heavy Metal Ion Desalination",slug:"infrared-analysis-of-electrostatic-layer-by-layer-polymer-membranes-having-characteristics-of-heavy",signatures:"Weimin Zhou, Huitan Fu and Takaomi Kobayashi",authors:[{id:"110384",title:"Dr.",name:"Takaomi",middleName:null,surname:"Kobayashi",fullName:"Takaomi Kobayashi",slug:"takaomi-kobayashi"}]},{id:"36181",title:"Infrared Spectroscopy as a Tool to Monitor Radiation Curing",slug:"infrared-spectroscopy-as-a-tool-to-monitor-radiation-curing",signatures:"Marco Sangermano, Patrick Meier and Spiros Tzavalas",authors:[{id:"112286",title:"Dr.",name:"Spiros",middleName:null,surname:"Tzavalas",fullName:"Spiros Tzavalas",slug:"spiros-tzavalas"},{id:"114382",title:"Prof.",name:"Marco",middleName:null,surname:"Sangermano",fullName:"Marco Sangermano",slug:"marco-sangermano"},{id:"114384",title:"Dr",name:"Patrick",middleName:null,surname:"Meier",fullName:"Patrick Meier",slug:"patrick-meier"}]},{id:"36182",title:"Characterization of Compositional Gradient Structure of Polymeric Materials by FTIR Technology",slug:"characterization-of-compositional-gradient-structure-of-polymeric-materials-by-ft-ir-technology",signatures:"Alata Hexig and Bayar Hexig",authors:[{id:"20867",title:"Dr.",name:"Bayar",middleName:null,surname:"Hexig",fullName:"Bayar Hexig",slug:"bayar-hexig"},{id:"111986",title:"Dr.",name:"Alata",middleName:null,surname:"Hexig",fullName:"Alata Hexig",slug:"alata-hexig"}]},{id:"36183",title:"Fourier Transform Infrared Spectroscopy - Useful Analytical Tool for Non-Destructive Analysis",slug:"fourier-trasform-infrared-spectroscopy-useful-analytical-tool-for-non-destructive-analysis",signatures:"Simona-Carmen Litescu, Eugenia D. Teodor, Georgiana-Ileana Truica, Andreia Tache and Gabriel-Lucian Radu",authors:[{id:"24425",title:"Dr.",name:"Simona Carmen",middleName:null,surname:"Litescu",fullName:"Simona Carmen Litescu",slug:"simona-carmen-litescu"},{id:"24429",title:"Prof.",name:"Gabriel-Lucian",middleName:null,surname:"Radu",fullName:"Gabriel-Lucian Radu",slug:"gabriel-lucian-radu"},{id:"108318",title:"Dr.",name:"Eugenia D.",middleName:null,surname:"Teodor",fullName:"Eugenia D. Teodor",slug:"eugenia-d.-teodor"},{id:"108323",title:"Dr.",name:"Georgiana-Ileana",middleName:null,surname:"Badea",fullName:"Georgiana-Ileana Badea",slug:"georgiana-ileana-badea"},{id:"136337",title:"Ms.",name:"Andreia",middleName:null,surname:"Tache",fullName:"Andreia Tache",slug:"andreia-tache"}]},{id:"36184",title:"Infrared Spectroscopy in the Analysis of Building and Construction Materials",slug:"infrared-spectroscopy-of-cementitious-materials",signatures:"Lucia Fernández-Carrasco, D. Torrens-Martín, L.M. Morales and Sagrario Martínez-Ramírez",authors:[{id:"107401",title:"Dr.",name:"Lucia J",middleName:null,surname:"Fernández",fullName:"Lucia J Fernández",slug:"lucia-j-fernandez"}]},{id:"36185",title:"Infrared Spectroscopy Techniques in the Characterization of SOFC Functional Ceramics",slug:"infrared-spectroscopy-techniques-in-the-characterization-of-sofc-functional-ceramics",signatures:"Daniel A. Macedo, Moisés R. Cesário, Graziele L. Souza, Beatriz Cela, Carlos A. Paskocimas, Antonio E. Martinelli, Dulce M. A. Melo and Rubens M. Nascimento",authors:[{id:"102015",title:"MSc.",name:"Daniel",middleName:null,surname:"Macedo",fullName:"Daniel Macedo",slug:"daniel-macedo"},{id:"112309",title:"MSc",name:"Moisés",middleName:"Romolos",surname:"Cesário",fullName:"Moisés Cesário",slug:"moises-cesario"},{id:"112310",title:"Ms.",name:"Graziele",middleName:null,surname:"Souza",fullName:"Graziele Souza",slug:"graziele-souza"},{id:"112311",title:"MSc.",name:"Beatriz",middleName:null,surname:"Cela",fullName:"Beatriz Cela",slug:"beatriz-cela"},{id:"112312",title:"Prof.",name:"Carlos",middleName:null,surname:"Paskocimas",fullName:"Carlos Paskocimas",slug:"carlos-paskocimas"},{id:"112314",title:"Prof.",name:"Antonio",middleName:null,surname:"Martinelli",fullName:"Antonio Martinelli",slug:"antonio-martinelli"},{id:"112315",title:"Prof.",name:"Dulce",middleName:null,surname:"Melo",fullName:"Dulce Melo",slug:"dulce-melo"},{id:"112316",title:"Dr.",name:"Rubens",middleName:"Maribondo Do",surname:"Nascimento",fullName:"Rubens Nascimento",slug:"rubens-nascimento"}]},{id:"36186",title:"Infrared Spectroscopy of Functionalized Magnetic Nanoparticles",slug:"infrared-spectroscopy-of-functionalized-magnetic-nanoparticles",signatures:"Perla E. García Casillas, Claudia A. Rodriguez Gonzalez and Carlos A. Martínez Pérez",authors:[{id:"104636",title:"Dr.",name:"Perla E.",middleName:null,surname:"García Casillas",fullName:"Perla E. García Casillas",slug:"perla-e.-garcia-casillas"},{id:"112440",title:"Dr.",name:"Carlos A.",middleName:null,surname:"Martínez Pérez",fullName:"Carlos A. Martínez Pérez",slug:"carlos-a.-martinez-perez"},{id:"112441",title:"Dr.",name:"Claudia A.",middleName:null,surname:"Rodriguez Gonzalez",fullName:"Claudia A. Rodriguez Gonzalez",slug:"claudia-a.-rodriguez-gonzalez"}]},{id:"36187",title:"Determination of Adsorption Characteristics of Volatile Organic Compounds Using Gas Phase FTIR Spectroscopy Flow Analysis",slug:"determination-of-adsorption-characteristics-of-volatile-organic-compounds-using-gas-phase-ftir-spect",signatures:"Tarik Chafik",authors:[{id:"107310",title:"Prof.",name:"Tarik",middleName:null,surname:"Chafik",fullName:"Tarik Chafik",slug:"tarik-chafik"}]},{id:"36188",title:"Identification of Rocket Motor Characteristics from Infrared Emission Spectra",slug:"identification-of-rocket-motor-characteristics-from-infrared-emission-spectra",signatures:"N. Hamp, J.H. Knoetze, C. Aldrich and C. Marais",authors:[{id:"112229",title:"Prof.",name:"Chris",middleName:null,surname:"Aldrich",fullName:"Chris Aldrich",slug:"chris-aldrich"},{id:"112232",title:"Prof.",name:"Hansie",middleName:null,surname:"Knoetze",fullName:"Hansie Knoetze",slug:"hansie-knoetze"},{id:"135327",title:"Ms.",name:"Corne",middleName:null,surname:"Marais",fullName:"Corne Marais",slug:"corne-marais"}]},{id:"36189",title:"Optical Technologies for Determination of Pesticide Residue",slug:"optical-technology-for-determination-of-pesticide-residue",signatures:"Yankun Peng, Yongyu Li and Jingjing Chen",authors:[{id:"113343",title:"Prof.",name:"Yankun",middleName:null,surname:"Peng",fullName:"Yankun Peng",slug:"yankun-peng"},{id:"116636",title:"Dr.",name:"Yongyu",middleName:null,surname:"Li",fullName:"Yongyu Li",slug:"yongyu-li"},{id:"116637",title:"Dr.",name:"Jingjing",middleName:null,surname:"Chen",fullName:"Jingjing Chen",slug:"jingjing-chen"}]},{id:"36190",title:"High Resolution Far Infrared Spectra of the Semiconductor Alloys Obtained Using the Synchrotron Radiation as Source",slug:"high-resolution-spectra-of-semiconductor-s-alloys-obtained-using-the-far-infrared-synchrotron-radi",signatures:"E.M. Sheregii",authors:[{id:"102655",title:"Prof.",name:"Eugen",middleName:null,surname:"Sheregii",fullName:"Eugen Sheregii",slug:"eugen-sheregii"}]},{id:"36191",title:"Effective Reaction Monitoring of Intermediates by ATR-IR Spectroscopy Utilizing Fibre Optic Probes",slug:"effective-reaction-monitoring-of-intermediates-by-atr-ir-spectroscopy-utilizing-fibre-optic-probes",signatures:"Daniel Lumpi and Christian Braunshier",authors:[{id:"109019",title:"Dr.",name:"Christian",middleName:null,surname:"Braunshier",fullName:"Christian Braunshier",slug:"christian-braunshier"},{id:"111798",title:"MSc.",name:"Daniel",middleName:null,surname:"Lumpi",fullName:"Daniel Lumpi",slug:"daniel-lumpi"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"73628",title:"Novel Biosensing Strategies for the in Vivo Detection of microRNA",doi:"10.5772/intechopen.93937",slug:"novel-biosensing-strategies-for-the-in-vivo-detection-of-microrna",body:'MicroRNA (miRNA) is a kind of endogenous non-coding RNA with a length of 18–25 nucleic acid sequences. It is usually integrated into the RNA-induced silencing complex (RISC) to execute its biological function of degrading mRNA or inhibiting transcription. MicroRNA is highly conservative and has strict temporal and spatial specificity. It plays a key regulatory role in the development of animals and plants, cell proliferation, differentiation and apoptosis, immunity and metabolism, angiogenesis, tumor invasion, and metastasis. Mature miRNA has the disadvantages of the small fragment, no poly (A), high similarity among family members, and low expression level. As a result, it is difficult to sensitively and accurately detect miRNA. Therefore, it is very important to establish fast and simple methods with high sensitivity and specificity for miRNA detection [1].
Many miRNA analysis methods, including polymerase chain reaction (PCR), DNA Microarray, and Northern blotting have been developed. Although these traditional strategies are the gold standard methods for miRNA identification, detection, and analysis in vitro, it is very difficult for them to achieve accurate and sensitive spatiotemporal information of miRNA in living organisms. Therefore, in this chapter, we summarize the novel strategies for biosensing miRNAs in vivoincluding hybridization probe assays, strand-displacement reaction (SDR), entropy-driven DNA catalysis (EDC), catalytic hairpin assembly (CHA), hybridization chain reaction (HCR), DNAzyme-mediated assays and CRISPR-mediated assays. These contents involve their principles and methods, including their advantages and shortcomings, to provide important help for the further study of related detection technology.
Northern blotting, invented by Alwine in 1979, is the first established method to identify and detect miRNA. It is widely used to detect the expression of miRNAs of various sizes from long primitive miRNAs to mature miRNAs. In the process, the miRNA was separated by polyacrylamide gel electrophoresis in total RNA, then transferred to the imprinted membrane, hybridized with the radionuclide labeled probe. The RNA molecule of interest is detected by the signal of labeled probe. This method can detect both the quantity and the length of miRNA, but it has some defects such as cumbersome operation, low sensitivity, time-consuming, and large sample consumption, which limits its application in clinical diagnosis.
To improve the detection sensitivity, Válóczi et al. [2] employed locked nucleic acid (LNA) probe instead of traditional oligonucleotide probe to enhance the affinity and stability of the nucleotide double strand. Pall et al. [3] utilized 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride crosslinking method instead of the traditional UV crosslinking method to improve the binding efficiency of miRNA and nylon membrane. The method of biotin labeling instead of isotope labeling was used to conduct chemiluminescence detection and reduce radioactive pollution [4].
The microarray, developed in the early 1990s, enables the high-throughput miRNA detection in a parallel fashion. In this method, the target miRNA is incubated and hybridized with multiple probes (complementary to the target miRNA sequence) on a chip. After removing the non-hybridized part, the signal can be detected and analyzed by fluorescence scanning or northern blotting [5]. DNA probe-based microarray usually consumes a large amount of samples and has disadvantages such as low sensitivity and specificity and false positives caused by cross-reactions. However, LNA probe can reduce the consumption of starting materials and improve the sensitivity and accuracy of microarray [6]. Furthermore, liquid suspension microsphere hybridization can effectively avoid cross-reaction in the solid chip to decrease the occurrence of false positives.
Quantitative real-time polymerase chain reaction (qRT-PCR) is one of the main methods to detect low abundance miRNA with high sensitivity and accuracy [7]. The principle of this method is to reversely transcribe miRNA into the corresponding cDNA that is used as a template to initiate real-time PCR and then indirectly analyze miRNA by detecting the signal of amplified products [8].
Because the miRNA sequence is short (18 ~ 25 nt) and similar to the length of PCR primers, researchers overcome this shortcoming by introducing stem-ring primers for reverse transcription [9] or adding poly (A) into RNA to initiate reverse transcription and dyeing with SYBR Green. Besides, pri-miRNA and pre-miRNA can be introduced into qRT-PCR, causing inaccurate quantification [10]. qRT-PCR usually requires complex primer design and precise reaction temperature control, thereby greatly increasing the cost and complexity of the experiment.
Although the traditional miRNA detection methods are widely used in miRNA detection, there are still some shortcomings such as complex operation, low sensitivity, poor specificity, and large sample consumption. These shortcomings greatly limited the application of these methods in clinical diagnosis and treatment. Importantly, these approaches are only applied to the in vitro measurement of miRNA.
Hybridization probe assay is a simple and direct detection method without amplification of target miRNA. The principle of this method is as follows: firstly, miRNA is fixed in the tissue or cell. Secondly, signal-labeled nucleic acid probes are added and hybridized with the miRNA based on the principle of complementary pairing. Finally, the position of target miRNA to be detected in the tissue or cell is displayed by certain detection means.
With the principle of hybridization, Wang et al. [11] combined the excellent fluorescence-quenching ability of Ti3C2 nanosheets with double-labeled DNA fluorescent probes to design a chimeric DNA-functionalized Ti3C2 nanoprobe. When this probe crosses the cell membrane, TAMRA-labeled plasma membrane glycoprotein MUC1 aptamer interacted with MUC1 and peeled off from Ti3C2, lighting up red fluorescence. In the cytoplasm, FAM-tagged hairpin DNA hybridized with miR-21, leading to green fluorescence recovery. This strategy can perform in vitro measurement of miR-21 and MUC1 with nanomolar sensitivity and in situ simultaneous imaging of dual biomarkers in living cells. Although Ti3C2 greatly reduces the fluorescence background, the sensitivity of the probe is still limited because one target miRNA only restores the fluorescence of one fluorescent molecule.
To further improve the detection and imaging sensitivity, fluorescence double-labeling and double-quenching strategy is undoubtedly a good design. Molecular beacon (MB) is a hairpin-structure DNA probe. Its two ends are labeled with two identical fluorescent molecules. When MB is in a close state, a self-quenching effect between two fluorescent molecules occurs. Graphene oxide (GO) is a good fluorescence quencher. The electrostatic interaction between the DNA probe and GO also quenches effectively the fluorescence of the DNA probe. Based on the aforementioned properties of MB and GO, Yang et al. [12] designed an MB-GO fluorescent sensor for sensitive imaging of intracellular miRNA (Figure 1). Two Cy5 fluorophores were tagged at both ends of MB. MB was electrostatically adsorbed on the surface of GO through the π-π stacking effect. Two Cy5 fluorophores were quenched through their self-quenching effect and cy5-GO resonance energy transfer, which greatly reduced the fluorescence background of the sensing system. Once target miRNA hybridize with MB probes, hairpin-structure MBs were unfolded to separate two Cy5 molecules and the MB-miRNA complex with rigid structure was released from the surface of GO, recovering fluorescence signal and significantly enhancing the detection sensitivity (Limit of detection, LOD = 30 pM). This method also visualized miRNA-21 in cancer cells and three xenograft tumor models.
Illustration of 2Cy5-MB-GO complex sensing miRNA in living cells. Reprinted with permission from ref 12. Copyright 2018 American Chemical Society.
Another approach to enhance the sensitivity of the hybridization probe assay is to use the plasmon coupling effect of assembled nanostructures, especially, dissymmetric nanostructures. Xu et al. [13] developed a plasmonic nanorod probe by miR-21-directed in situ self-assembly of DNA-modified Gold nanorods (AuNR) in living cells. The formation of NR@PS-PAA dimers gives rise to intense chiroplasmonic signal and surface-enhanced Raman scattering (SERS). The LOD was 0.081 fmol/10μgˑRNA (CD signal) and 1.12 fmol/10μgˑRNA (SERS signal), respectively. Highly sensitive quantitative analysis and in situ imaging of microRNA in cells are achieved.
Mechanism of in vivo imaging microRNA of the DNA-fueled and catalytic molecular machine. Reprinted with permission from ref 19. Copyright 2017 American Chemical Society.
Although the introduction of nanomaterials (gold nanoparticles, graphene oxide, upconversion nanoparticles, MnO2 nanosheets, quantum dots, silver nanoparticles, noble metal nanoclusters, and silica nanoparticles) remarkably enhanced the sensitivity of hybridization probe assay, the lack of signal amplification limits its practical application in the sensitive detection of intracellular miRNA.
Strand displacement reaction (SDR) is a dynamic process of hybridization-driven DNA strand exchange accompanied by branch migration [14]. In this process, a single-stranded reactant (input, target miRNA) reacts with a multi-stranded DNA complex and releases another single-stranded product (output signal) and a new DNA complex. This process operates autonomously through a series of reversible DNA hybridization and dissociation steps to produce numerous output strands, thereby generating cascaded signal amplification [15, 16].
Using SDR, Wang et al. [17] constructed a double-stranded fuel catalyzed DNA molecular machine. The machine was divided into two parts: the first part was composed of the Cy5-labeled signal strand and BHQ-2 labeled complementary quenching strand. The second part was double-strand fuel (DSF), consisting of fuel strand and protected fuel. The target miRNA bound to the quenched strand and triggered the first SDR to obtain the miRNA-quenching double-strand, releasing the signal strand to recover the fluorescence. At this time, DSF initiated the second SDR, the dominated fuel hybridized with quencher strand, replacing miRNA to produce double-stranded waste and intermediated miRNA protected fuel. The new signal strand can combine with the protected fuel to release miRNA again and repeated the above-mentioned cycle reaction. Thus, the target miRNA was continuously released from intermediate 2 and circularly participated in the subsequent reaction to achieve signal amplification. This method has high sensitivity, strong signal amplification ability, and relatively low background signal.
Ma et al. [18] similarly developed an artificial intelligence signal amplification system (AISA). The system also consists of a fluorescence-quenching double-strand and fuel-protection double strand. It underwent a three-steps reaction: miRNA replaced the signal strand and combined with the quenching strand, the fuel strand replaced miRNA and combined with the quenching strand, and new signal strand replaced miRNA to achieve the reuse of it (the last two steps of the reaction could be recycled to produce amplified signal). Based on this principle, they built two AISA systems to detect Hsa-miR-100 and Hsa-miR-484, respectively. Their versatility and feasibility were proved to be actively used in disease diagnosis and treatment, evaluation, stem cell tracking, and other fields, but the design of the probe was cumbersome.
In recent years, the combination of SDR and nanomaterials for miRNA detection has become a hot spot. Li et al. [19] constructed dsDNA-AuNPs nanoprobes using toehold strand displacement reaction (TSDR) to attain the amplification detection of trace let-7a in living cells (Figure 2). The molecular catalytic machine contained dsDNA-AuNPs nanoprobes and DNA fuel strands, while the dsDNA contained an unfolded hairpin sequence labeled with FAM and TAMRA at both ends. Binding to the linker strand of the dsDNA, the target miRNA replaced the hairpin to restore its folded structure. Forster resonance energy transfer (FRET) signal occurred between the fluorescent groups. At the same time, the target miRNA was recycled by cascaded strand displacement reactions realizing the amplification and detection signal of the target miRNA. Zhang et al. [20] developed a kind of dendritic mesoporous silica nanoparticles encapsulated by tumor cell (MCF-7) membrane (DMSN-DP@CM) and simultaneously modified with DNA photoacoustic probe and fuel strand. The target miRNA triggered the release of the near-infrared fluorescence strand from the quenched strand and the fuel strand further replaced the target miRNA. The alternate replacement of target miRNA and DNA fuel strand generated an amplified photoacoustic signal ratio to realize the miRNA detection.
Surface-enhanced Raman spectroscopy (SERS) refers to that when molecules approach the metal surface of nanostructures, the Raman signal of molecules is enhanced. Gold nanoparticles with the core-satellite structure are important SERS substrate structures, which are composed of a single Au (or Ag) inside and multiple Au (or Ag) linked outside. The core-satellite structure is combined with SDR to detect miRNA and produce the SERS signal.
Li et al. [21] designed the core-satellite plasma rulers (PRs) for the quantitative determination of miRNA-21 in living cells. Several small gold nanoparticles were assembled on large gold nanoparticles with dsDNA to form a core-satellite. MiRNA-21 initiated a single hybridization event, leading to the destruction of core-satellite structural components. The plasma displacement between the core and the satellite initiated the wavelength changing of scattering intensity. The expression and the amount of miRNA-21 could be detected via statistical analysis of the wavelength signal. This method enabled highly sensitive detection of the intracellular miRNA without side effects.
Gold nanorods have strong and controllable plasma resonance properties, which can be widely used in photothermal therapy and amplification detection of miRNA. Qu et al. [22] used the assembly of Ag2S on the surface of platinum (Pt)-modified gold nanorods (AuNR-Pt) to form a nuclear-satellite structure (AuNR-Pt@Ag2S). The probe can complete the near-infrared imaging of miRNA in vivo. Target miRNA bound to the complementary DNA sequence and released the strand modified with Ag2S, thereby destroying the core-satellite structure and recovering the fluorescence. The LOD was 0.0082 amol ngRNA−1, providing a multifunctional nanoplatform for tumor diagnosis and treatment in vivo.
Inspired by Qu’s work, Yan et al. [23] utilized the electrostatic interaction between polyethyleneimine (PEI)-modified gold nanorod and nucleic acid probe to construct a Fuel Improved miRNA Explorer (FIRE) sensing platform. The detection system included a double-strand DNA labeled with BHQ-2, Cy5 fluorescence-quenching group, and a fuel strand that realizing the cycling of miRNA for signal amplification. The target miRNA triggered the release of dsDNA to recover fluorescence. In this design, the preparation of FIRE is simple via electrostatic interactions. Moreover, AuNRs enhanced the photoacoustic imaging and real-time monitoring capabilities of FIRE, resulting in the sensitive detection of miRNA and effective tumor treatment effect.
In addition to the strand displacement reaction catalyzed by fuel strand, toehold-mediated strand displacement is another commonly used amplification strategy. A novel catalytic self-assembly nanosensor based on quantum dots was constructed [24] to detect miRNA in vivo. As an efficient catalyst, miRNA triggered the toehold-mediated strand displacement cascade reaction to produce multiple Cy5/biotin double-labeled dsDNA, which were assembled on a 605QD surface, resulting in significant FRET signal. The nanosensor was simple to operate and has high specificity and sensitivity. Also, the synergistic effect between telomerase and the catalytic strand was helpful to distinguish cancer cells from normal cells, which provided a valuable method for clinical diagnosis.
Enzyme-mediated strand displacement reaction enables the exponential accumulation of DNA products through the continuous polymerization-nicking-displacement cycle process catalyzed by polymerases. Based on the amplification methods, Yang et al. [25] proposed a novel strategy by utilizing branched DNA ligation enhanced isothermal strand displacement polymerization (B-ICSDP) for in vitro quantitation and intracellular miRNA imaging. This internal Y-shaped DNA structure consisted of a circular DNA scaffold and three repeatable molecular beacons (MB). MiRNA triggered the conformation conversion of MB and recovered the fluorescence. Additionally, polymerase-based cyclic SDR produced a large number of extended Y-type DNA structures (one DNA scaffold could hybridize with three MBs), thus generating amplified signals. This method had the advantages of high sensitivity, high specificity, and simple design. Besides, it could be used to detect single or multiple target miRNAs in living cells.
Peng’s team [26] developed a telomerase-catalyzed FRET ratio probe for accurate miRNA detection. AuNPs were modified with a capture probe containing recognition sequence and telomerase primer located at the 5′ of the capture probe strand. The detection probe (a molecular beacon labeled with donor FAM and acceptor TARMA) hybridized with the capture probe, separating the fluorescent donor and acceptor and causing low FRET signal. Once miRNA specifically recognized and hybridized the capture probe. The detection probe was then replaced by miRNA to form a stem-ring structure. Thus, the FAM and TAMRA were brought in close proximity to produce a high FRET signal. In addition, the capture probe was extended with telomerase primers and hybridized with the catalytic strand to displace target miRNA. The released miRNA also triggered the above-mentioned detection system. This method had a low background signal and can detect low abundance miRNA molecules in living cells.
Catalytic hairpin assembly (CHA) is an enzyme-free, hairpin fuel-driven, and autonomous nucleic acid amplification technology. A CHA system needs to design two hairpin structures according to the sequence of target miRNA [27]. One segment of the first hairpin is complementary to the target miRNA sequence [28]. Its hairpin structure can be unfolded by miRNA, and then form a complementary structure with another hairpin probe. The target miRNA will be replaced and dissociated, which can further catalyze CHA between other hairpin probes, forming a cycle to generate amplification signal. The catalytic hairpin assembly has been widely used in nucleic acid detection due to its enzyme-free and target-recyclable advantages.
Like SDR, CHA usually employs nanomaterials as a scaffold and carrier to deliver DNA probes into living cells. As shown in Figure 3, Liu et al. [29] developed a core-satellite nanoprobe (AuNPs-AuNDs CS). Hairpin1 (H1) was immobilized on the Au nanoparticle surface (AuNPs-H1, satellites) and hairpin2 (H2) was assembled on the surface of the plasmonic gold nanodumbbells (AuNDs-H2, core) via Au − S bonds. MiRNA triggered CHA by targeting AuNPs-H1 (AuNPs-H1-miRNA). AuNDs-H2 then hybridized with AuNPs-H1-miRNA to form a core-satellite nanostructure, whereas target miRNA was displaced from AuNPs-H1-miRNA. The released miRNA originated the next assembly of AuNPs-AuNDs CS, generating an amplified signal. This design engineered metallic nanoparticle aggregates to increase electromagnetic hot spots, thereby realizing the highly-sensitive SERS detection of low abundant miRNA.
Schematic representation of (A) the Assembly process of AuNPs-AuNDs-CS and (B) AuNPs-AuNDs-CS sensing miRNA and imaging in living cells. Reprinted with permission from ref 29. Copyright 2018 American Chemical Society.
Wang et al. [30] modified the fluorescence-labeled hairpin H1 to the surface of AuNPs. The fluorescence of H1 was quenched by AuNPs. When the probes were delivered into cells, the hybridization between H1 and miRNA unfolded H1. The exposed single-strand domain of H1 induced H2 (hairpin fuel) hybridization and displaced miR-21. The released miR-21 participated in the subsequent reaction cycle. The sensitivity of hairpin-fuelled catalytic nanobeacons is two orders of magnitude lower than that of noncatalytic nanobeacons.
Aruni et al. [31] exploited a genetically encoded means to design an RNA-based CHA circuit for imaging miRNA in living cells. In this design, Broccoli, a specific RNA aptamer for DFHBI-1 T, was used as a fluorescence reporter. It was split into two non-fluorescent parts (Broc and Coli). Broc was attached to the 5′ end of H1, while Coli was conjugated to the 3′ end of H2. The target miRNA initiated CHA and hybridized with H1. The unfolded H1 then hybridized with H2 to displace target miRNA and form dsDNA. The recombinant Broccoli activated the dye DFHBI-1 T to emit fluorescence, and the target miRNA can be recycled to catalyze the fluorescence of ten to hundreds of broccolis, achieving signal amplification. This strategy provided a new opportunity for the application of gene-encoded RNA circuits in cells.
To improve the kinetics and efficiency of CHA in the complex intracellular environment, inspired by spatial-confinement effects of cells, Liu et al. [32] constructed a three-dimensional DNA nanocube to implement the localized hairpin-DNA cascade signal amplification. The hairpin H1 and H2 labeled with Cy3 and Cy5 were modified in the cube, respectively. MiRNA could specifically unfold H1 and then unfold H2. The rapid and efficient imaging of miRNA could be monitored by FRET. This cascade amplifier significantly improved the speed (7 times faster) and efficiency (2.6 times higher) of signal amplification. Furthermore, this probe possesses good cell permeability, good nuclease resistance, and the ability to avoid false-positive signals.
The hybridized chain reaction proposed by Dirks and Pierce in 2004 is an isothermal signal amplification technology based on DNA strand displacement reaction [33]. Single strand promoter DNA (target miRNA) binds to the stem-loop nucleic acid probe and causes conformation changing of hairpin DNA. The unfolded hairpin structure can unfold a new DNA hairpin. Two kinds of stem-loop probes were alternately hybridized to form double-stranded DNA containing a large number of repeat units [34]. This method has the advantages of constant temperature, efficient signal amplification, and without the requirement of the enzyme. It has been applied to the detection of DNA or RNA.
Wang et al. [35] combined CHA with HCR to design a sensing system with six DNA hairpins (Figure 4). Target miRNA first catalyzed CHA and formed numerous double-stranded products (H1∙H2) containing initiator sequences to initiate downstream HCR circuit. The resultant dsDNA products then triggered subsequently autonomous cross-hybridization reactions to form HCR copolymer (H3∙H4∙H5∙H6). The resultant HCR copolymer carries many donor-acceptor pairs that can generate FRET signal. The synergistic amplification effect of the CHA-HCR system significantly increased the selectivity and sensitivity of miRNA detection.
Schematic of the isothermal CHA–HCR cascaded circuit for miRNAs assay. Adapted with permission from ref 35. Copyright 2018 Royal Society of Chemistry.
Exploiting the signal amplification function of protein with multiple binding sites, Huang et al. [36] used streptavidin (SA) as a protein scaffold and four biotinylated hairpin DNA probes to construct a DNA tetrads probe. When miRNA was present, miRNA unfolded the Cy3-labeled hairpin H1, triggered HCR, and hybridized with Cy5-labeled H2 to form a cross-linked hydrogel network, generating the signal. It is proved that the DNA tetrad was a highly robust delivery agent and could realize the sensitive imaging of miRNA.
To improve the stability of the miRNA sensing system, Wu and coworkers [37] designed a DNA probe composed of tripartite Y-shaped DNA structures, folate probe FAP and hairpin probe H1, H2. MiRNA triggered H1 and H2 hairpin probes to assemble HCR, separating Cy5 and BHQ-2 labeled on H1 to recover fluorescence signal. This method was proved to have high sensitivity with a sub-picomolar limit in vitro, and the probe had high stability in vivo.
Entropy-driven DNA catalysis (EDC) exponentially amplifies DNA signal by target-induced entropy change of the pre-design sensing system [38]. EDC is a simple, rapid, and enzyme-free isothermal signal amplification technology based on toehold exchange mechanism and adaptable to different low-abundance targets due to its modular design and tunability.
An EDC system usually is composed of a three-strand substrate complex (output strand and signal strand are complementary with link strand) and a fuel strand [39]. In the absence of targets, the sensing system does not work because the toehold domain in the substrate that binds to the fuel strand has been protected. As a catalyst, miRNA can combine with the substrate link strand to replace the signal strand, and then the fuel strand replaced miRNA to be recycled. The production of liberated molecules leads to an increase of entropy, repeating the abovementioned strand displacement reaction to generate amplified signals.
Liang et al. [40] constructed an entropy-driven DNA nanomachine. A three-stranded substrate complex (A/B/C) and an affinity ligand (L) were modified on the AuNP surface, respectively. Target miRNA hybridized with L to replace B from C. A fuel strand (F) bound to C and the C-F complex departed from the AuNP surface, restoring the fluorescence of the FAM-labeled C strand. Thus, such entropy-driven catalytic DNA nanomachine operated automatically and progressively to realize signal amplification. The assay had superior sensitivity (LOD = 8 pM) due to the accelerated intramolecular reaction.
To avoid the addition of external enzyme or fuel transfection, Lu et al. [41] developed a NIR-controlled DNA sensing system based on entropy-driven catalysis to detect intracellular miRNA. Hollow copper sulfide nanoparticle (HCuSNPs) served as the photothermal conversion agent and a carrier. An entropy-driven DNA probe and DNA fuel were conjugated to HCuSNPs. Under the irradiation of the near-infrared laser, target miRNA-155 recognized toe1 and combined with the probe, replaced Cy3-DNA and exposed toe2 that initiates toehold-mediated strand displacement reactions. Cy3-DNA was released and its fluorescence was recovered. This method possessed facile design and its sensitivity is two orders of magnitude higher than that of molecular beacons (MBs).
DNAzyme is a kind of DNA with catalytic function and structure recognition ability. It was screened by Breaker and Joyce through the systematic evolution of ligands by exponential enrichment (SELEX) technology in 1994. The single strand, simulating the function of enzymes in vivo, can catalyze different chemical reactions, including nucleic acid cleavage, nucleic acid ligation, phosphorylation, porphyrin metallization enzyme activity, and peroxidase activity. It has high catalytic efficiency, simple modification of fluorescent dyes, and strong chemical stability. Also, compared with the traditional protease, DNAzyme can be denaturated repeatedly and renatured without loss of enzyme activity. DNAzyme catalytic amplification technology is a constant temperature amplification technology, which is especially suitable for high sensitivity detection of intracellular targets.
Wu et al. [42] constructed a signal-enhanced split DNAzyme probe loaded on gold nanoparticles for miRNA detection in living cells. They split Mg2+-dependent DNAzyme into two nucleic acid strands, which were hybridized with the substrate to form a complex. The fluorescence of the complex was quenched without target miRNA. In the presence of miRNA, two split strands hybridized with target miRNA to form a secondary structure with catalytic activity, cleaving the substrate to separate fluorescence reporter and quenching groups and restoring fluorescence. The released miRNA targeted the next DNAzyme probe and switched on recognition-cleavage-release cycles to produce signal amplification. In this experiment, the split DNAzyme serves as both a recognition element and a signal reporter. As a carrier, gold nanoparticles increase the biological affinity of nanoprobe and avoid the degradation of the nucleic acid probe in the process of transport into cells. This method improved the detection sensitivity and specificity. Additionally, it had low cytotoxicity, high enzymatic degradation resistance which is effective for detection in living cells.
Yang et al. [43] integrated DNAzyme, its substrate, and recognition strand into a FAM-labeled hairpin-locked-DNAzyme probe. The probe was immobilized on the surface of gold nanoparticles. The catalytic activity of DNAzyme was inhibited and the fluorescence of FAM was quenched by gold nanoparticles. When target miRNA hybridized with the hairpin probe, the change of the probe structure activated the DNAzyme to cleave the substrate strand and made the FAM-labeled substrate strand emit fluorescence. After the miRNA was released, it entered the next cycle and generated amplification signals. This design significantly reduced fluorescent background signal. The detection limit of the target miRNA was 25 pM. It can be applied to the in vivo detection of different types of miRNA.
Although AuNP-DNA probes are highly sensitive and selective, they suffer from the aggregation of AuNPs in the complex intracellular environment. To overcome this limitation, there is highly desirable for homogeneous DNA (composed entirely of DNAs) sensing system. Xue et al. [44] utilized a Y-shaped backbone-rigidified triangular DNA scaffold (YTDS) to develop a self-powered DNAzyme walker (Figure 5). This sensing platform consists of YTDS (carrier), nuclide aptamer (transportation), and a locked M-DNAzyme-substrate complex (recognition and signal reporter). The binding of miRNA trigger the DNAzyme walker to perform self-powered stepwise walking and amplify the signal at the same time. The detection platform has the advantages of efficient delivery without any transfection agent and amplification of the output signal without any protein enzyme.
(A) The preparation routes of Ap-YTDS-DzW. (B) Ap-YTDS-DzW imaging of miRNAs in vivo. Reprinted with permission from ref 44. Copyright 2019 American Chemical Society.
To effectively protect the probe from degradation by nuclease and greatly improve its cell permeability, Li et al. [45] constructed a DNAzyme probe based on the tetrahedral nanostructure. FAM and Dabcyl were labeled the linker strand and partial complementary strand, respectively. The catalytic activity of the DNAzyme was effectively silenced by the locking strand in the absence of target miRNA. The target miRNA hybridized with the locking strand to release DNAzyme. With the assist of the Na+ cofactor, the substrate strand was cleaved and the fluorescence was recovered. Activated DNAzyme could compete with an inactive DNAzyme for the next locking strand, starting the next hybridization, and generating amplified signals circularly. The LOD of the DNAzyme probe is 16 pM. It possessed high specificity and distinguished target miRNA from its family members.
The catalytic activity of DNAzyme depends on the concentration of its cofactor Mg2+. However, the content of Mg2+ in the cell is too low to support the long-time catalytic reactions used for the signal amplification. To circumvent this limitation, Wei et al. [46] constructed a smart autocatalytic DNAzyme imaging machinery to execute magnetic resonance imaging (MRI) of miRNA in vivo. The imaging system is composed of honeycomb-like MnO2 nanosponge (hMNS), HCR, and autocatalytic DNAzyme. In this system, hMNS acts as three roles, that is, nanocarrier, DNAzyme cofactors, and MRI agents. The multifunctional hMNS effectively delivered the system into the cells and was degraded into Mn2+ by intracellular glutathione (GSH) as a DNAzyme cofactor. MiR-21 activates HCR amplification to produce DNAzyme nanowires, mediating the automatic catalytic accumulation of the new trigger and the retroaction to the original HCR sensor. This robust assay can accurately locate miRNAs in vivo and enhance the amplification signal.
CRISPR/Cas9 system is a new gene-editing technology based on the bacterial adaptive immune defense system. It can insert or delete genes accurately to knock out target genes [47]. CRISPR/Cas9 system consists of CRISPR RNA, transactivating crRNA, and endonuclease Cas9. Cas9 is specific to the protospacer adjacent motif with the guidance of crRNA and tracrRNA to form RNA–DNA complex. Cas9 can cut double-stranded DNA to complete gene editing.
For the convenience of operation, scientists fused the mature tracrRNA-crRNA dual structure into a sgRNA, its 5′ strand sequence is complementary to the target miRNA, and the 3′ stranded structure could bind to Cas9. Therefore, only one sgRNA needs to be designed to edit the related genes. This method has some advantages such as simple operation, high efficiency, low cost, and no introduction of foreign genes. So far, it has become the most popular gene-editing technology. Similarly, this method has been applied to the detection of miRNA.
Wang et al. [48] constructed a CRISPR–Cas9 sensing platform based on a miRNA-mediated sgRNA releasing strategy. The sensing approach successfully realized miRNA imaging and cell-specific regulation of the CRISPR gene editing system. The sensing system was divided into two parts. One part was composed of Cas9 or Cas9 mutant fusion protein to edit or inhibit gene expression, the other was sgRNA with miRNA binding site without activity, mediating the binding of Cas9 protein in a specific position of the genome. As a result, only specific miRNA could finish the cleavage reaction, producing mature sgRNA, and starting the CRISPR system. The system could sense two kinds of miRNAs in the same cell and turn on red or green fluorescence respectively. It was proved that the detection platform could accomplish precise regulation of different gene sites by multiple miRNAs and provided new ideas for other gene therapy technologies.
An ideal method for detecting intracellular miRNA should possess high throughput, high specificity, high detection sensitivity, wide detection range, and low detection cost. To achieve this goal, a variety of miRNA detection methods have been developed, but there are many shortcomings, and the technology needs to be improved. The additionally introduced nanomaterials are self-aggregated and enriched in different tissues in a complex living environment. The hybridization probe assay lacks signal amplification capabilities. SDA, HCR, and CHA need to avoid high background signals caused by probe leakage. DNAzyme-mediated assays usually require exogenous cofactors to initiate signal amplification. Therefore, EDC and CRISPR-mediated assays are the most promising detection methods of miRNA in vivo in the future. The establishment of an ideal miRNA detection technology still needs the efforts of scientists and the continuous progress of related science and technology.
The authors gratefully acknowledge the National Natural Science Foundation of China (No. 31972772) and the Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, China (ZZ-A11).
There are no conflicts to declare.
The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
",metaTitle:"Open Access Publishing Fees",metaDescription:"Open Access Publishing Fees",metaKeywords:null,canonicalURL:"/page/OA-publishing-fees",contentRaw:'[{"type":"htmlEditorComponent","content":"As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 118,000 international scientists and researchers.
\\n\\nThe Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
\\n\\nOAPF Publishing Options
\\n\\n*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\\n\\nServices included are:
\\n\\nSee our full list of services here.
\\n\\nWhat isn't covered by the Open Access Publishing Fee?
\\n\\nIf your manuscript:
\\n\\nYour Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\\n\\nOpen Access Funding
\\n\\nTo explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\\n\\nFor Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\\n\\nAdded Value of Publishing with IntechOpen
\\n\\nChoosing to publish with IntechOpen ensures the following benefits:
\\n\\nBenefits of Publishing with IntechOpen
\\n\\nAs a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 118,000 international scientists and researchers.
\n\nThe Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
\n\nOAPF Publishing Options
\n\n*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\nServices included are:
\n\nSee our full list of services here.
\n\nWhat isn't covered by the Open Access Publishing Fee?
\n\nIf your manuscript:
\n\nYour Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\nOpen Access Funding
\n\nTo explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at oapf@intechopen.com for further details or assistance.
\n\nFor Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\nAdded Value of Publishing with IntechOpen
\n\nChoosing to publish with IntechOpen ensures the following benefits:
\n\nBenefits of Publishing with IntechOpen
\n\n