Commercial dairy products and ingredients with health or function claims based on CPP content (source: modified from [16]).
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{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"},{slug:"suf-and-intechopen-announce-collaboration-20200331",title:"SUF and IntechOpen Announce Collaboration"}]},book:{item:{type:"book",id:"6778",leadTitle:null,fullTitle:"Electrocatalysts for Fuel Cells and Hydrogen Evolution - Theory to Design",title:"Electrocatalysts for Fuel Cells and Hydrogen Evolution",subtitle:"Theory to Design",reviewType:"peer-reviewed",abstract:"The book starts with a theoretical understanding of electrocatalysis in the framework of density functional theory followed by a vivid review of oxygen reduction reactions. A special emphasis has been placed on electrocatalysts for a proton-exchange membrane-based fuel cell where graphene with noble metal dispersion plays a significant role in electron transfer at thermodynamically favourable conditions. The latter part of the book deals with two 2D materials with high economic viability and process ability and MoS2 and WS2 for their prospects in water-splitting from renewable energy.",isbn:"978-1-78984-813-7",printIsbn:"978-1-78984-812-0",pdfIsbn:"978-1-83881-705-3",doi:"10.5772/intechopen.72563",price:119,priceEur:129,priceUsd:155,slug:"electrocatalysts-for-fuel-cells-and-hydrogen-evolution-theory-to-design",numberOfPages:128,isOpenForSubmission:!1,isInWos:1,hash:"0bee36d692b3ce00b11fef507609d521",bookSignature:"Abhijit Ray, Indrajit Mukhopadhyay and Ranjan K. Pati",publishedDate:"December 5th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6778.jpg",numberOfDownloads:7762,numberOfWosCitations:1,numberOfCrossrefCitations:3,numberOfDimensionsCitations:12,hasAltmetrics:0,numberOfTotalCitations:16,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 13th 2017",dateEndSecondStepPublish:"January 10th 2018",dateEndThirdStepPublish:"March 4th 2018",dateEndFourthStepPublish:"May 23rd 2018",dateEndFifthStepPublish:"July 22nd 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"174737",title:"Dr.",name:"Abhijit",middleName:null,surname:"Ray",slug:"abhijit-ray",fullName:"Abhijit Ray",profilePictureURL:"https://mts.intechopen.com/storage/users/174737/images/6417_n.jpg",biography:"Associate Professor in Solar Energy Materials and Devices at Pandit Deendayal Petroleum University (PDPU), India and heading Department of Solar Energy. He received his MSc in Physics from University of Kalyani (India) and PhD in experimental condensed matter physics from Indian Institute of Technology, Kharagpur (India) in 2003. After completing his PhD, he was post doctoral researcher at Variable Energy Cyclotron Center of Department of Atomic Energy (India). In 2004 he joined Birla Institute of Technology, Mesra as Lecturer in Physics and joined PDPU in 2007 as Assistant Professor. He has also been visiting professor at Nagoya Institute of Technology, Japan during 2015-16. His current research works are focused on the development of earth-abundant and less toxic semiconducting thin films, nanostructures and devices for photovoltaic, photo-electrochemical, electrocatalytic conversions and capacitive energy storage applications. He has been principle investigator in four externally funded research projects; published more than 48 papers in peer reviewed journals and filed 3 Indian patents.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Pandit Deendayal Petroleum University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"239748",title:"Dr.",name:"Indrajit",middleName:null,surname:"Mukhopadhyay",slug:"indrajit-mukhopadhyay",fullName:"Indrajit Mukhopadhyay",profilePictureURL:"https://mts.intechopen.com/storage/users/239748/images/8090_n.png",biography:"Prof. Indrajit Mukhopadhyay is a Professor of PDPU, heading the Solar Research and Development Center at PDPU. He has been involved in establishing a modern laboratory with state-of-the-art facilities for carrying out frontier research in the field of solar photovoltaics.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:{id:"239747",title:"Dr.",name:"Ranjan Kumar",middleName:null,surname:"Pati",slug:"ranjan-kumar-pati",fullName:"Ranjan Kumar Pati",profilePictureURL:"https://mts.intechopen.com/storage/users/239747/images/8091_n.jpg",biography:"Dr. Ranjan K. Pati is an Assistant Professor at the School of Petroleum Technology, PDPU. His research focuses are nanomaterials, oxide ceramics, and their application on fuel cell technology.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"505",title:"Electrochemistry",slug:"chemistry-physical-chemistry-electrochemistry"}],chapters:[{id:"61933",title:"Theoretical Basis of Electrocatalysis",doi:"10.5772/intechopen.77109",slug:"theoretical-basis-of-electrocatalysis",totalDownloads:1803,totalCrossrefCites:1,totalDimensionsCites:4,signatures:"Chi Ho Lee and Sang Uck Lee",downloadPdfUrl:"/chapter/pdf-download/61933",previewPdfUrl:"/chapter/pdf-preview/61933",authors:[null],corrections:null},{id:"62242",title:"Oxygen Reduction Reaction",doi:"10.5772/intechopen.79098",slug:"oxygen-reduction-reaction",totalDownloads:2715,totalCrossrefCites:1,totalDimensionsCites:2,signatures:"Lindiwe Khotseng",downloadPdfUrl:"/chapter/pdf-download/62242",previewPdfUrl:"/chapter/pdf-preview/62242",authors:[null],corrections:null},{id:"61784",title:"Active Sites Derived from Heteroatom Doping in Carbon Materials for Oxygen Reduction Reaction",doi:"10.5772/intechopen.77048",slug:"active-sites-derived-from-heteroatom-doping-in-carbon-materials-for-oxygen-reduction-reaction",totalDownloads:2127,totalCrossrefCites:1,totalDimensionsCites:2,signatures:"Winston Duo Wu and Dan Xu",downloadPdfUrl:"/chapter/pdf-download/61784",previewPdfUrl:"/chapter/pdf-preview/61784",authors:[null],corrections:null},{id:"63442",title:"Noble Metal Dispersed on Reduced Graphene Oxide and Its Application in PEM Fuel Cells",doi:"10.5772/intechopen.80941",slug:"noble-metal-dispersed-on-reduced-graphene-oxide-and-its-application-in-pem-fuel-cells",totalDownloads:583,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"Adriana Marinoiu, Mircea Raceanu, Elena Carcadea, Aida Pantazi,\nRaluca Mesterca, Oana Tutunaru, Simona Nica, Daniela Bala, Mihai\nVarlam and Marius Enachescu",downloadPdfUrl:"/chapter/pdf-download/63442",previewPdfUrl:"/chapter/pdf-preview/63442",authors:[null],corrections:null},{id:"62641",title:"Electrocatalytic Properties of Molybdenum and Tungsten Alloys in the Hydrogen Evolution Reaction",doi:"10.5772/intechopen.79058",slug:"electrocatalytic-properties-of-molybdenum-and-tungsten-alloys-in-the-hydrogen-evolution-reaction",totalDownloads:543,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"Valeriy Kublanovsky and Yuliya Yapontseva",downloadPdfUrl:"/chapter/pdf-download/62641",previewPdfUrl:"/chapter/pdf-preview/62641",authors:[null],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"21",title:"Ferroelectrics",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"ferroelectrics",bookSignature:"Indrani Coondoo",coverURL:"https://cdn.intechopen.com/books/images_new/21.jpg",editedByType:"Edited by",editors:[{id:"289832",title:"Dr.",name:"Indrani",surname:"Coondoo",slug:"indrani-coondoo",fullName:"Indrani Coondoo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2549",title:"Ion Exchange Technologies",subtitle:null,isOpenForSubmission:!1,hash:"d5d70a346ca433c501e5968f54286740",slug:"ion-exchange-technologies",bookSignature:"Ayben Kilislioğlu",coverURL:"https://cdn.intechopen.com/books/images_new/2549.jpg",editedByType:"Edited by",editors:[{id:"139903",title:"Prof.",name:"Ayben",surname:"Kilislioglu",slug:"ayben-kilislioglu",fullName:"Ayben Kilislioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2282",title:"Atomic Force Microscopy",subtitle:"Imaging, Measuring and Manipulating Surfaces at the Atomic Scale",isOpenForSubmission:!1,hash:"17fb7c8076806f6aca457071b7e7ce10",slug:"atomic-force-microscopy-imaging-measuring-and-manipulating-surfaces-at-the-atomic-scale",bookSignature:"Victor Bellitto",coverURL:"https://cdn.intechopen.com/books/images_new/2282.jpg",editedByType:"Edited by",editors:[{id:"111789",title:"Dr.",name:"Victor",surname:"Bellitto",slug:"victor-bellitto",fullName:"Victor Bellitto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5381",title:"Ionic Liquids",subtitle:"Progress and Developments in",isOpenForSubmission:!1,hash:"e87c37c4d014c11121453605e6d0f37a",slug:"progress-and-developments-in-ionic-liquids",bookSignature:"Scott Handy",coverURL:"https://cdn.intechopen.com/books/images_new/5381.jpg",editedByType:"Edited by",editors:[{id:"42658",title:"Prof.",name:"Scott",surname:"Handy",slug:"scott-handy",fullName:"Scott Handy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"607",title:"Electropolymerization",subtitle:null,isOpenForSubmission:!1,hash:"0457c6cc64766bdd64f8195b8e22afb1",slug:"electropolymerization",bookSignature:"Ewa Schab-Balcerzak",coverURL:"https://cdn.intechopen.com/books/images_new/607.jpg",editedByType:"Edited by",editors:[{id:"73293",title:"Dr.",name:"Ewa",surname:"Schab-Balcerzak",slug:"ewa-schab-balcerzak",fullName:"Ewa Schab-Balcerzak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1431",title:"Recent Trend in Electrochemical Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"9ec6b0bf8c309891f70a9c181399984e",slug:"recent-trend-in-electrochemical-science-and-technology",bookSignature:"Ujjal Kumar Sur",coverURL:"https://cdn.intechopen.com/books/images_new/1431.jpg",editedByType:"Edited by",editors:[{id:"27764",title:"Dr.",name:"Ujjal Kumar",surname:"Sur",slug:"ujjal-kumar-sur",fullName:"Ujjal Kumar Sur"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"159",title:"Superconductivity",subtitle:"Theory and Applications",isOpenForSubmission:!1,hash:"bb0587d06c5516fc4e3c89818b9b17e6",slug:"superconductivity-theory-and-applications",bookSignature:"Adir Moyses Luiz",coverURL:"https://cdn.intechopen.com/books/images_new/159.jpg",editedByType:"Edited by",editors:[{id:"10012",title:"Dr.",name:"Adir",surname:"Luiz",slug:"adir-luiz",fullName:"Adir Luiz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1455",title:"Electroplating",subtitle:null,isOpenForSubmission:!1,hash:"18ec8cf0e50c5e8170a9d0b20af09b7f",slug:"electroplating",bookSignature:"Darwin Sebayang and Sulaiman Bin Haji Hasan",coverURL:"https://cdn.intechopen.com/books/images_new/1455.jpg",editedByType:"Edited by",editors:[{id:"92970",title:"Prof.",name:"Darwin",surname:"Sebayang",slug:"darwin-sebayang",fullName:"Darwin Sebayang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4599",title:"Ion Exchange",subtitle:"Studies and Applications",isOpenForSubmission:!1,hash:"2e45cfed818bc38f70a214561b0a1e21",slug:"ion-exchange-studies-and-applications",bookSignature:"Ayben Kilislioglu",coverURL:"https://cdn.intechopen.com/books/images_new/4599.jpg",editedByType:"Edited by",editors:[{id:"139903",title:"Prof.",name:"Ayben",surname:"Kilislioglu",slug:"ayben-kilislioglu",fullName:"Ayben Kilislioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3476",title:"Developments in Electrochemistry",subtitle:null,isOpenForSubmission:!1,hash:"a0d070ce0c17777f7605b91a0beac07e",slug:"developments-in-electrochemistry",bookSignature:"Jang H. Chun",coverURL:"https://cdn.intechopen.com/books/images_new/3476.jpg",editedByType:"Edited by",editors:[{id:"164636",title:"Prof.",name:"Jang Ho",surname:"Chun",slug:"jang-ho-chun",fullName:"Jang Ho Chun"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"73639",slug:"corrigendum-to-single-photon-emission-computed-tomography-spect-radiopharmaceuticals",title:"Corrigendum to: Single-Photon Emission Computed Tomography (SPECT) Radiopharmaceuticals",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/73639.pdf",downloadPdfUrl:"/chapter/pdf-download/73639",previewPdfUrl:"/chapter/pdf-preview/73639",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/73639",risUrl:"/chapter/ris/73639",chapter:{id:"73033",slug:"single-photon-emission-computed-tomography-spect-radiopharmaceuticals",signatures:"Syed Ali Raza Naqvi and Muhammad Babar Imran",dateSubmitted:"May 13th 2019",dateReviewed:"July 22nd 2020",datePrePublished:"August 21st 2020",datePublished:null,book:{id:"7769",title:"Medical Isotopes",subtitle:null,fullTitle:"Medical Isotopes",slug:"medical-isotopes",publishedDate:"January 7th 2021",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",fullName:"Syed Ali Raza Naqvi",slug:"syed-ali-raza-naqvi",email:"drarnaqvi@gmail.com",position:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"302793",title:"Dr.",name:"Muhammad Babar",middleName:null,surname:"Imran",fullName:"Muhammad Babar Imran",slug:"muhammad-babar-imran",email:"muhammadbabarimran@yahoo.com",position:null,institution:null}]}},chapter:{id:"73033",slug:"single-photon-emission-computed-tomography-spect-radiopharmaceuticals",signatures:"Syed Ali Raza Naqvi and Muhammad Babar Imran",dateSubmitted:"May 13th 2019",dateReviewed:"July 22nd 2020",datePrePublished:"August 21st 2020",datePublished:null,book:{id:"7769",title:"Medical Isotopes",subtitle:null,fullTitle:"Medical Isotopes",slug:"medical-isotopes",publishedDate:"January 7th 2021",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",fullName:"Syed Ali Raza Naqvi",slug:"syed-ali-raza-naqvi",email:"drarnaqvi@gmail.com",position:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"302793",title:"Dr.",name:"Muhammad Babar",middleName:null,surname:"Imran",fullName:"Muhammad Babar Imran",slug:"muhammad-babar-imran",email:"muhammadbabarimran@yahoo.com",position:null,institution:null}]},book:{id:"7769",title:"Medical Isotopes",subtitle:null,fullTitle:"Medical Isotopes",slug:"medical-isotopes",publishedDate:"January 7th 2021",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10848",leadTitle:null,title:"Tribology",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:!0,hash:"316ca42e0526e3c775e16b929cc702f9",bookSignature:"",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10848.jpg",keywords:null,numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 25th 2020",dateEndSecondStepPublish:"December 16th 2020",dateEndThirdStepPublish:"February 14th 2021",dateEndFourthStepPublish:"May 5th 2021",dateEndFifthStepPublish:"July 4th 2021",remainingDaysToSecondStep:"a month",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:"14",title:"Materials Science",slug:"materials-science"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"6188",title:"Solidification",subtitle:null,isOpenForSubmission:!1,hash:"0405c42586170a1def7a4b011c5f2b60",slug:"solidification",bookSignature:"Alicia Esther Ares",coverURL:"https://cdn.intechopen.com/books/images_new/6188.jpg",editedByType:"Edited by",editors:[{id:"91095",title:"Dr.",name:"Alicia Esther",surname:"Ares",slug:"alicia-esther-ares",fullName:"Alicia Esther Ares"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6802",title:"Graphene Oxide",subtitle:"Applications and Opportunities",isOpenForSubmission:!1,hash:"075b313e11be74c55a1f66be5dd56b40",slug:"graphene-oxide-applications-and-opportunities",bookSignature:"Ganesh Kamble",coverURL:"https://cdn.intechopen.com/books/images_new/6802.jpg",editedByType:"Edited by",editors:[{id:"236420",title:"Dr.",name:"Ganesh Shamrao",surname:"Kamble",slug:"ganesh-shamrao-kamble",fullName:"Ganesh Shamrao Kamble"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6517",title:"Emerging Solar Energy Materials",subtitle:null,isOpenForSubmission:!1,hash:"186936bb201bb186fb04b095aa39d9b8",slug:"emerging-solar-energy-materials",bookSignature:"Sadia Ameen, M. Shaheer Akhtar and Hyung-Shik Shin",coverURL:"https://cdn.intechopen.com/books/images_new/6517.jpg",editedByType:"Edited by",editors:[{id:"52613",title:"Dr.",name:"Sadia",surname:"Ameen",slug:"sadia-ameen",fullName:"Sadia Ameen"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6320",title:"Advances in Glass Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6d0a32a0cf9806bccd04101a8b6e1b95",slug:"advances-in-glass-science-and-technology",bookSignature:"Vincenzo M. Sglavo",coverURL:"https://cdn.intechopen.com/books/images_new/6320.jpg",editedByType:"Edited by",editors:[{id:"17426",title:"Prof.",name:"Vincenzo Maria",surname:"Sglavo",slug:"vincenzo-maria-sglavo",fullName:"Vincenzo Maria Sglavo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10049",title:"Advanced Functional Materials",subtitle:null,isOpenForSubmission:!1,hash:"58745a56d54c143e4de8433f3d6eb62e",slug:"advanced-functional-materials",bookSignature:"Nevin Tasaltin, Paul Sunday Nnamchi and Safaa Saud",coverURL:"https://cdn.intechopen.com/books/images_new/10049.jpg",editedByType:"Edited by",editors:[{id:"94825",title:"Associate Prof.",name:"Nevin",surname:"Tasaltin",slug:"nevin-tasaltin",fullName:"Nevin Tasaltin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7666",title:"Synthesis Methods and Crystallization",subtitle:null,isOpenForSubmission:!1,hash:"cd26687924373b72a27a0f69e7849486",slug:"synthesis-methods-and-crystallization",bookSignature:"Riadh Marzouki",coverURL:"https://cdn.intechopen.com/books/images_new/7666.jpg",editedByType:"Edited by",editors:[{id:"300527",title:"Dr.",name:"Riadh",surname:"Marzouki",slug:"riadh-marzouki",fullName:"Riadh Marzouki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8812",title:"Contemporary Topics about Phosphorus in Biology and Materials",subtitle:null,isOpenForSubmission:!1,hash:"86c427901f631db034a54b22dd765d6a",slug:"contemporary-topics-about-phosphorus-in-biology-and-materials",bookSignature:"David G. Churchill, Maja Dutour Sikirić, Božana Čolović and Helga Füredi Milhofer",coverURL:"https://cdn.intechopen.com/books/images_new/8812.jpg",editedByType:"Edited by",editors:[{id:"219335",title:"Dr.",name:"David",surname:"Churchill",slug:"david-churchill",fullName:"David Churchill"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7960",title:"Assorted Dimensional Reconfigurable Materials",subtitle:null,isOpenForSubmission:!1,hash:"bc49969c3a4e2fc8f65d4722cc4d95a5",slug:"assorted-dimensional-reconfigurable-materials",bookSignature:"Rajendra Sukhjadeorao Dongre and Dilip Rankrishna Peshwe",coverURL:"https://cdn.intechopen.com/books/images_new/7960.jpg",editedByType:"Edited by",editors:[{id:"188286",title:"Associate Prof.",name:"Rajendra",surname:"Dongre",slug:"rajendra-dongre",fullName:"Rajendra Dongre"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7676",title:"Zeolites",subtitle:"New Challenges",isOpenForSubmission:!1,hash:"4dc664fa55f94b38c13af542041fc3cc",slug:"zeolites-new-challenges",bookSignature:"Karmen Margeta and Anamarija Farkaš",coverURL:"https://cdn.intechopen.com/books/images_new/7676.jpg",editedByType:"Edited by",editors:[{id:"216140",title:"Dr.",name:"Karmen",surname:"Margeta",slug:"karmen-margeta",fullName:"Karmen Margeta"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9321",title:"Advances in Microporous and Mesoporous Materials",subtitle:null,isOpenForSubmission:!1,hash:"d5b349cbde0b129c20f31dc02b94d33b",slug:"advances-in-microporous-and-mesoporous-materials",bookSignature:"Rafael Huirache Acuña",coverURL:"https://cdn.intechopen.com/books/images_new/9321.jpg",editedByType:"Edited by",editors:[{id:"181660",title:"Dr.",name:"Rafael",surname:"Huirache Acuña",slug:"rafael-huirache-acuna",fullName:"Rafael Huirache Acuña"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"38840",title:"Bioactive Casein Phosphopeptides in Dairy Products as Nutraceuticals for Functional Foods",doi:"10.5772/50725",slug:"bioactive-casein-phosphopeptides-in-dairy-products-as-nutraceuticals-for-functional-foods",body:'
Nutraceuticals, a term combining the words “nutrition” and “pharmaceutical”, is a food or food product that provides medical or health benefits including the prevention and treatment of diseases. A functional food essentially provides a health benefit beyond the basic nutrition, whereas nutraceutical is used to describe an isolated or concentrated molecular extract of bioactive compounds. Milk is a unique food providing a variety of essential nutrients necessary to properly fuel the body. Inactive food proteins can release encrypted bioactive peptides in vivo or in vitro by digestive enzymatic hydrolysis. Bioseparation protocols offer unique possibilities for a number of application areas, e.g., hydrolyzate-based nutraceutical ingredients for functional foods, dietary supplements and medical foods.
Many ingredients are included in the wide range of nutraceuticals, such as essential amino acids, conjugated fatty acids, vitamins, minerals and polyphenols. They have already been patented and incorporated in functional foods and nutritional beverages. Such components are believed to improve overall health and well-being, reducing the risk of specific diseases or minimizing the effects of other health concerns. However, milk is devoid of flavonoids, the most common group of vegetable polyphenolic compounds, which act as antioxidants and free radical scavengers. In contrast, the ingestion of soy and green tea extract may reduce the risk of developing prostate cancer and may protect against various other types of cancer [1-2]. An interesting patented invention has made available an extended-release form of polyphenols and riboflavin (vitamin B2) coated with methylcellulose [3]. Coating slows down the release of polyphenols in the nutraceutical preparation [3]. Possible applications of coating technology could be extended to all of the bioactive peptides susceptible to digestive enzymes. For example, glutathione can be maintained in human blood at normal levels by supplying it as dry-filled capsules [4]. Nutrients and bioactive compounds may be microencapsulated by using mixtures of proteins or peptides and oils. Encapsulation of ω-3 fatty acids (FA) enhances the stability and bioavailability of bioactive food ingredients [5]. By these means, new transparent bioavailable beverages containing ω-3 rich oils, phospholipids and minerals in an oxidatively stable food system were created [6]. Iron or calcium casein phosphopeptides (CPP) were embedded in the chitosan lactate fiber as a protective agent against oil oxidation [6]. A recent patent relates to a nutraceutical composition consisting of a sweetener admixture for food or drink comprising calcium lactate, calcium acetate, vitamin D3 and sucralose (for fortified zero calorie formulation) or sugar (white/brown; for fortified sugar preparation) [7]. Milk proteins playing a physiological role include proteins such as β-lactoglobulin, α-lactalbumin, immunoglobulins, lactoferrin, heat-stable proteose peptones, serum albumin and various acid soluble phosphoglycoproteins. Casein (CN), representing 80% of total milk proteins, consists of four αs1-, αs2-, β-, and κ-CN families in the approximate ratio 38:11:38:13. Research performed in recent years has shown that caseins and whey proteins are rich in encrypted biologically active peptides such as exorphins (casomorphins), CPP and immunopeptides [8]. The peptides are released by enzymes in the form of mature bioactive components or the precursors thereof [9]. They are 3- to 20-residue long peptides released during in vivo gastrointestinal digestion. Historically, the opioid peptides were discovered as the result of a systematic search for exogenous substances, namely (i) first discovered in 1979, opioid agonist peptides derived from milk proteins were characterized in 1986; (ii) in 1982, angiotensin-converting enzyme (ACE)-inhibitory peptides were found to be antihypertensive peptides; (iii) then, fibrinogen-like sequences with antithrombotic activity were found; (iv) phagocytic activity and lymphocyte proliferation of numerous immunomodulating peptides were observed; (v) CPP facilitating the absorption of minerals, especially calcium, magnesium and iron were found; and (vi) antimicrobial peptides were discovered [10]. There are many milk peptides that possess multifunctional activities, i.e., they can play two or more hormone-like roles. Bioactive peptides grouped according to their function in human well-being are shown in Figure 1.
Nutraceutical products comprising short bioactive peptides showing in vitro or in vivo antimicrobial, ACE-inhibitory activity and/or antihypertensive and/or antioxidant activity are being considered for possible use by the pharmaceutical industry. The CN hydrolyzates could serve as food preservatives to reinforce the body\'s natural defenses or as pharmaceutical products for facilitating the control of blood and/or bacterial infections [12]. Much research has been devoted to increasing mineral transport by phosphorylated groups of peptides [13]. CPP in commercial hydrolysed casein (Tatua Cooperative Dairy Co. Ltd, New Zealand and Arla Foods Ingredients and Sweden) seem to help the absorption of chelated calcium, iron, copper, zinc and manganese in the intestine (Table 1). Thus, CPP-bound amorphous calcium phosphate (ACP) displayed anticariogenic effect when added to dentifrices or oral care products by localizing calcium and phosphate ions at the tooth surface. Similarly, it has been claimed that a chewing gum or other confectionery product containing a combination of CPP-ACP and sodium bicarbonate as active ingredients can provide dental health benefits [14]. In experiments on humans, synthetic CPP-ACP nanocomplexes incorporated in mouth rinses and sugar-free chewing gums have been proven to be potential anticariogenic agents [15] (Table 1).
Main bioactivity of peptides formed by the enzymatic digestion of milk proteins (source: [11]).
Commercial dairy products and ingredients with health or function claims based on CPP content (source: modified from [16]).
Peptides with various bioactivities can be produced according to two different methods: i) in vitro fermentation of milk inoculated with starter cultures and ii) in vitro digestion of milk proteins by one or more proteolytic enzymes.
(i) The proteolytic system of lactococci is able to degrade milk proteins using cell-wall-bound proteinases by releasing di-, tri-, and/or oligo-peptides and amino acids supporting the growth of bacteria. In addition, lactococcal peptidases released into the curd/cheese consequently to autolysis can further degrade the internalized peptides to amino acids [17]. The higher the exopeptidase activity in cheeses, the greater the age of the cheese [18]. Consistently, yogurt and other cultured dairy drinks have some of the highest counts of cells that actually survived and thus possessed the lowest number of peptides derived from the aminopeptidase activity. In a comprehensive review of literature, no enzyme with carboxypeptidase (CPase) activity has been reported for either lactococci or other LAB [19-20]. The bacterial peptidases have different and partly overlapping specificities (Figure 2).
A simplified model presenting proteolysis, transport, peptidolysis and regulation of the proteolytic system of Lactococcus lactis on casein breakdown [20-22]. Intracellular peptidases PepO and PepF are endopeptidases, PepN/PepC/PepP are general aminopeptidases, PepX is X-prolyldipeptidyl aminopeptidase, PepT is tripeptidase, PepQ is prolidase, PepR is prolinase, PepI is proline iminopeptidase, and PepD and PepV are dipeptidases D and V. The role of PepN, PepC, PepI, PepP and PepA and PepO, PepF, PepX, PepQ, PepR, PepV, PepT and peptidolytic cycles are depicted schematically (various alternative routes of breakdown are possible for most peptides).
Although the intracellular endopeptidases PepN and PepC are unable to hydrolyze casein molecules, the X-prolyl dipeptidyl aminopeptidases (PepX) are active on oligopeptides hydrolyzing the internal bonds of casein-derived peptides. Taken together, these enzymes are able to remove the N-terminal residues from peptides, with the specificity primarily depending on the nature of the N-terminal amino acid [20-21]. Di- and tripeptides generated by endopeptidases, general aminopeptidases and PepX are next subjected to additional cleavage by the tripeptidase, PepT, and dipeptidases, PepV and PepD (Figure 2). Other peptidases with more specific substrate specificities include PepA, which liberates N-terminal acidic residues from 3- to 9-residue long peptides; PepP, which prefers tripeptides carrying proline in the middle position; PepR and PepI, which act on dipeptides containing proline in the penultimate position; PepQ, which cleaves dipeptides carrying proline in the second position; and PepS, which shows preference for peptides containing two to five residues with Arg or aromatic amino acid residues in the N-terminal position [20-21,23] (Figure 2). This proteolytic system is able to support LAB growth to high cell densities (109–1010 cfu/mL) in milk containing only small amounts of hydrolytic products that are transportable into the cells for assimilation. Lb. helveticus and Lb. delbrueckii ssp. bulgaricus possess cell wall proteinase activity stronger than that of lactococci. The number of intracellular proteins released by St.\n\t\t\t\tthermophilus is greater than that by Lb. helveticus [24]. Proteins released in cheese from a starter-based thermophilic LAB, such as Lb. helveticus, Lb. delbruecki subsp. lactis and Streptococcus salivarius subsp. thermophilus and Propionibacterium\n\t\t\t\tfreudenreichii, have been identified using 2D-PAGE and mass spectrometry (MS) analysis [24]. Similarly, bioactive peptides have been determined using High Performance Liquid Chromatography (HPLC) and offline Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry-Time-Of-Flight (MALDI-MS-TOF) [25]. These peptides were all generated from CN and released upon proteolysis depending on the bacterial strain [26]. In this manner, proteinases play a primary role, as they are able to generate specific bioactive peptides. Recombinant human αs1-casein digested by trypsin gave rise to several ACE-inhibitory peptides and calcium-binding CPP. These peptides did not form in cheese whey, although they can be formed from CN during fermentation using various commercial dairy starters [27]. The combination of the LAB bacteria and proteolytic enzymes could serve to increase the range of bioactive peptides.
(ii) In vitro\n\t\t\t\thydrolysis of CN by pepsin and trypsin could produce many bioactive peptides. Pepsin, an endopeptidase with broad specificity, preferentially cleaves hydrophobic, preferably aromatic, residues. Trypsin specifically hydrolyses peptide bonds just after a lysine or an arginine residue of β-casein A1 and A2 variant (11 and 4, respectively); κ-casein A and B (9 and 5); αs2-CN A (24 and 6); or αs1-CN B (14 and 6). In this manner, tryptic hydrolysates of CN contain uneven peptides of up to 8159 Da and also free amino acids [28]. We have demonstrated that CN hydrolysate by pepsin (P) and trypsin (T) in succession does not contain peptides with molecular mass greater than 2431 Da. β-CN resulted extensively hydrolyzed into a high number of oligopeptides by using proteases with well defined cleavage specificity. Controlled partial hydrolysis by proteinases could lead to the formation of partially degraded proteins critical for obtaining new functional products. The choice of digestion enzymes needs to be evaluated carefully because influences the hydrolysate final composition. A high number of peptides with antimicrobial, anti-hypertensive and opiod-like activity has been identified (Table 2), some of which exactly matched those described in the literature for potential bioactivity (Table 2). The potent opioid β-CM7 peptide retained part of its original opioid activity-like food hormone when progressively shortened. The synthetic β-casomorphin derivatives have been shown to be highly specific and potent β-type opioid receptor ligands [29].
We also performed sequential milk protein (powder sample) digestions using various endoproteases facilitating a consistent partial hydrolysis. The high degree of specificity in terms of cleaving peptide bonds exhibited by a cocktail of enzymes (P, T and P432 from Biocatalysts, U.K) yielded a limited number of CPP. After fractionation on an HA column, both non-CPP and CPP were identified as shown in Table 3. Different oxidation rates of Met residues in the same protein resulted in formation of the peptides with different molecular mass. In most cases, a single Met-containing peptide and its oxidized counterpart were identified. However, in many cases, when proteins contained several consecutive endoprotease sensitive bonds, different long peptides containing the same Met-oxidation site(s) were identified. The data in Table 3 suggest that the cocktail enzymes containing amino- and CPases, in addition to P and T, progressively reduce the size of peptides without altering the degree of phosphorylation. Evaluation of protein/peptide quality can take advantage of the tandem MS for the detection of native, partly oxidized and partly dephosphorylated peptides.
Identity of bioactive peptides found in the PT digest of milk protein powder sample. The bioactivity of the peptide from which they derive and the references are reported.
By this means, phosphorylated peptides (2 and 3P/mole) of a precursor of lactophorin (LP) (28 kDa milk glycoprotein), proteose-peptone component 3, and glycosylation-dependent adhesion molecule 1 were detected. In addition, three low molecular weight non-CPP derived from LP were detected.
Native milk proteins used as the substrate for digestion by enzymes did not form CPP. This suggests that denatured LP and other whey proteins could have the tendency to form low molecular-mass peptide aggregates characterized by a poor solubility. For this reason, the use of milk protein and/or any milk substrate powder must be discouraged to eliminate phosphates and salts from the substrate. The enzymatic hydrolysis of the casein implies the use of endoproteases. However, the protein hydrolysate with alcalase is used in infant formulae, dietetic foods, nutraceuticals, ice creams, dressings, fermented products, yogurts, and personal care products. CPP released by alcalase are truncated with respect to those released by trypsin. The identified peptides can be categorized into two groups, one containing multiphosphorylated peptides and the other tri-, di- and mono CPP. Each group contained a number of variously long peptides due to the broad specificity of alcalase cleaving peptide bonds mainly on the carboxyl side of Glu, Met, Leu, Tyr, Lys, and Gln. The exoproteases responsible for the hydrolysis are inactivated by heating for ~10 min to ~85 °C. The in vitro sequential use of pepsin, pancreatic proteases and extracts of human intestinal brush border membranes, mimicking the respective gastric, duodenal and jejuneal in vivo digestion of CN, exhibited significant bioactive effects. A limited number of CN and whey protein peptides survived the in vitro simulated gastro-intestinal digestion. The anionic character seems to confer a marked resistance to multi-phosphorylated CPP hydrolysis by endoprotease. Ten out of 19 CPP contained SerP available for binding minerals, and four of these peptides, αs1-CN (f57-90)5P, αs1-CN (f56-90)5P, αs1-CN (f55-76)5P, β-CN (f1-52)5P, were reported for the first time in the CN digests [42]. Only β-CN (f1-25)4P, 3P and 2P survived the simulated gastrointestinal digest of CN [43].
The ingress of foreign material in general, such as CPP, across the mucosal brush-border into the enterocyte is conditioned by the efficient dephosphorylation of peptides by alkaline phosphatase. This aspect deserves more in-depth investigation.
Native and partly Met-oxidized CPP isolated from a three enzyme (Pepsin, trypsin and P432) milk protein hydrolyzate.
Among the biologically active peptides, CPP characterized by SerP and/or ThrP residues account for ~30% of monoesters of hydroxyl amino acids. They mainly occur in the Ser/Thr-Xaa-SerP/Glu/Asp sequence consensus, where Xaa is any amino acid residue but Pro. The three-phosphorylated motif -SerP-SerP-SerP-Glu-Glu- occurs in αs1-CN (f66-70), αs2-CN (f8-12), αs2-CN (f56-60), and β-CN (f17-21). According to the current CN nomenclature, bovine αs1-CN, αs2-CN, β-CN, and κ-CN possess 8-9, 11-13, 4-5, and 1-2 phosphate (P) residues, respectively, and the P number could change according to the casein variant [44]. For example, β-CN D has one SerP residue less than the A counterpart due to the substitution Lys18 → Ser18.
The in vivo digestion of milk proteins takes place mainly in the stomach under the action of pepsins, gastric digestive proteinases that are able to digest ~20% proteins. Afterwards, the pepsin digests pass to the duodenum where peptides are further hydrolyzed by pancreatic enzymes. The digestion is completed by membrane proteases and a variety of peptidases embedded in the brush border of the small intestine and released by the intestinal microflora. These peptidases release an amino acid residue or a dipeptide from the N- and C-terminal side of oligopeptides [45-47]. Phosphatase(s) located in the brush border of the apical membrane of enterocytes, act(s) in removing phosphate groups, thus promoting partial or full peptide dephosphorylation of peptides in different body districts. The phosphorylated sequence is responsible, at the intestinal pH, for binding Ca++, Zn++, and Mg++ and for the in vivo resistance of the complex to gastrointestinal proteases [48]. Fe complexed to β-CN (f15-25)4P was scarcely hydrolyzed throughout the digestion, suggesting that the coordination of iron ions to CPP inhibits the action of both phosphatase and peptidases [49]. Brush border enzyme alkaline phosphatase activity could improve the absorption of Fe complexed CPP by releasing Fe from peptides. Moreover, Fe complexed to β-CN CPP was absorbed more than Fe complexed to αs1-CN CPP [50]. The differences in protein composition between cow and breast milk could explain some of the differences in the Fe bioavailability of the latter [50]. Iron deficiency, a major worldwide nutritional problem, can be reduced by CPP. Fe complexed CPP prevents the formation of poorly absorbed high molecular weight ferric hydroxides. Zinc absorption can also be enhanced by the formation of Zn complexed to CCP, in particular to β-CN (f1-25)4P [51]. Some portion of the mineral complexed CPP formed in the small intestine was resistant to the digestive and enteric bacteria enzymes and found in the feces of rats fed a casein-based diet [52]. Although literature data regarding intestinal CPP absorption are conflicting, the peptides seem to interact directly with the plasma membrane. One possible mode of CPP action on the transmembrane flux of calcium is that CPP might insert themselves into the plasma membrane and form their own calcium selective channels or act as calcium-carrier peptides rapidly internalized via endocytosis or other processes and eventually provide ionized calcium in the cytosol [53]. Cellular uptake studies of fluorine-18 labeled CPP in human colorectal adenocarcinoma cell line (HT-29) and human head and neck squamous cell carcinoma line (FaDu) cells at 37 °C and 48 °C showed a poor cell penetration because of the poor transport of the phosphopeptides through the cell membrane [54]. The results from in vivo studies are still too controversial, as there are many factors affecting Ca availability, such as the various co-present dietary compounds in the intestinal lumen [55]. Despite the vigor of the saturable active transport process by the duodenum, most of the absorption of ingested calcium occurs in the ileum (88% of calcium), jejunum (4%) and duodenum (8%) [56]. An important factor determining the contribution of the ileum to overall calcium absorption is the relatively long transit time of calcium in the segments of the small intestine, accounting for approximately 102 min in the ileum and 6 min in the duodenum [57]. The higher absorption of calcium occurred when inorganic P was added to the Ca-CPP preparation. CPP exhibit a potent ability to form soluble complexes with Ca2+ and other trace elements, preventing the formation of Ca-phosphate precipitate in the intestine. CPP could limit the inhibitory effect of phosphate on Ca availability and increase Ca transport across the distal small intestine [55]. All components of the diet reaching the ileum make calcium soluble or keep it in solution within the ileum. Several molecules, particularly CPP, stimulate the passive diffusion of minerals. CPP have been for the first time detected in human ileostomy fluid, confirming their ability to survive gastrointestinal passage into the human distal ileum [58]. CPP released during milk digestion appeared to be stable for up to 8 h in ileostomy contents [58]. The in vivo formation of bovine CPP was demonstrated in the small intestinal fluid of minipigs after ingestion of a diet containing casein [59] and in the stomach and duodenum after ingestion of milk or yogurt [60]. The in vivo survival of CPP to the prolonged intestinal passage in the distal small intestine is a prerequisite for their function as bioactive substances [58]. CPP are protected from degradation in the gut by the milk matrix, provided that they are ingested as milk constituents and not as isolated CPP. Whole casein or individual casein fractions are used as raw materials to obtain CPP as dietary supplements. Ca could be bound to either SerP or Glu residues [61], suggesting that CPP may enhance the solubility of calcium in the intestinal lumen, thereby increasing the mineral availability for absorption in the small intestine [62,13]. Chemically synthesized CPP, i.e., β-CN (f1-25)4P and αs1-CN (f59-79)5P, carrying the characteristic cluster Ser(P)-Ser(P)-Ser(P)-Glu-Glu, increase the intracellular calcium uptake by the human cultured HT-29 tumor cells [63], Caco-2 cells [64] and osteoblasts [65]. A more pronounced effect has been observed for β-CN-derived peptides than for αs1-CN-counterparts. It has been suggested that CPP promote calcium binding, which would depend on the structural conformation conferred by the two phosphorylated ‘acidic motif’ and the N-terminal sequence of β-CN [63].
Dental caries are initiated via the demineralization of tooth hard tissue by organic acids directly from the diet or produced from fermentable carbohydrate by dental plaque cariogenic bacteria. CPP can help to replace the minerals that were previously lost consequently to caries [66-67]. Hence, there is a great interest in developing CPP as nutraceutical ingredients for the formulation of functional foods.
CPP preferably comprise components released by four different casein families, each having a molecular weight greater than 500 Da. Multiply and singly, tryptic CPP can be simultaneously detected using MALDI-TOF, and the location of phosphate groups by a combination of tandem mass spectrometry and computer-assisted database search programs, such as SEQUEST (Trademark, University of Washington, Seattle Wash) [68-69]. Nano-electrospray MS/MS has been used for phosphopeptide sequencing and exact determination of phosphorylation sites [70]. However, mass spectrometric analysis of proteolytic digests of proteins rarely provides full coverage of the phosphorylated sequence, with parts of the sequence often going undetected. In addition, protein phosphorylation is often sub-stoichiometric, such that ionization of CPP present in lower abundance in complex hydrolysates is ordinarily suppressed by strongly ionizable non-phosphorylated peptides. The MALDI-MS desorption/ionization efficiency for phosphopeptides was reported to be an order of magnitude lower than that recorded for the non-phosphorylated counterpart, and ionization became more difficult as the number of phosphate groups increased [71]. Direct analysis of phosphopeptides utilizes two orthogonal MS scanning techniques, both based on the production of phosphopeptide-specific marker ions at m/z 63 and/or 79 in the negative ion mode. These scanning methods combined with the liquid chromatography (LC)-electrospray mass spectrometry (ESI) and nano-electrospray MS/MS allow the selective detection and identification of phosphopeptides even in complex proteolytic digests. Thus, even when the signal of the phosphopeptide is indistinguishable from the background, as in the conventional MS scan, low-abundant and low-stoichiometric phosphorylated peptides can be selectively determined in the presence of a large excess of non-phosphorylated peptides. This strategy is particularly well suited to phosphoproteins that are phosphorylated to varying degrees of stoichiometry at multiple sites [72]. However, the identification and characterization of phosphoproteins would be greatly improved using selective enrichment of CPP prior to MS analysis. An ancient technique for phosphoprotein enrichment consisted of the precipitation of phosphopeptides as insoluble barium salts and recovery by centrifugation, as according to the Manson & Annan method [73]. High-throughput phosphoproteome technologies currently rely on combining pre-separation of proteins, most commonly by high-resolution two-dimensional polyacrylamide gel, in-gel tryptic cleavage of proteins, and subsequent MALDI-TOF or ESI-MS/MS mass spectrometry analysis of peptides [74]. The high resolving power of 2-DE with the sensitive MS requires extensive manual manipulation of samples. Alternative methods are based on chemical derivatization. For example, for β-elimination, a strong base such as NaOH or Ba(OH)2 is used to cleave the phosphoester bonds of phosphoserine and phosphothreonine and form dehydroalanine or dehydroaminobutyric acid, respectively, each able to react with different nucleophiles, such as ethanedithiol (EDT) or dithiothreitol (DTT). This procedure provides a considerably simpler method to enrich CPP. By using cross-linking reagents with affinity tags, such as biotin, interfering non-cross-linked peptides are eliminated, and CPP are highly enriched [75]. Although the chemical derivatization methods are highly selective, they are not widely applied in phosphoproteome studies due to sample loss by the multiple reaction steps and unavoidable side reactions [76]. Immobilized metal-ion affinity chromatography (IMAC, with Fe3+, Ga3+, Ni2+ and Zr4+ metal ions) and metal oxide affinity chromatography (MOAC, with TiO2, ZrO2, Al2O3 and Nb2O5) have been widely used for the quantitative binding of CPP on resin or adsorbent. Iminodiacetic acid (IDA, a tridentate metal-chelator) or nitrilotriacetic acid (NTA, a quadradentate metal chelator) are often used as IMAC functional matrices reacting with multivalent metal ions to form chelated ions with positive charges useful for the purification of phosphopeptides. Usually Fe3+, Ga3+ and Al3+ are bound to a chelating support prior to fractionating the complex mixture of peptides before MS analysis [77-78]. Ga3+ showed selectivity for CPP higher than Fe3+ and Al3+ [77,79]. Phosphopeptides bound to IMAC resin are successively recovered in the column effluent by increasing either pH or the phosphate concentration in the buffer [80]. The negatively charged CPP selectively interact with TiO2 microspheres via bidentate binding at the dioxide surface [81-83]. TiO2-MOAC showed higher specificity than immobilized gallium (Ga3+), immobilized iron (Fe3+), or zirconium dioxide (ZrO2) affinity chromatography for phosphopeptide enrichment. The main problem associated with the chelating resins is the metal-ion leaching, which leads to CPP loss during the enrichment procedure. The selectivity of these methods was somewhat compromised by the detection of several acidic non-CPP that were also retained by the TiO2 column [84]. To overcome this drawback, the carboxyl groups are methyl esterified which eliminates the non-specific adsorption of acidic peptides on IMAC [85]. Considerable efforts have been expended to remove acidic non-CPP by washing the resin with 2,5-dihydroxybenzoic acid (DHB) [86] or phthalic acid [87]. It has been found that aliphatic hydroxyl acid modified metal oxide works more efficiently and more specifically than aromatic modifiers such as DHB and phthalic acid in titania and zirconia MOC [88]. However, all affinity techniques developed for the current enrichment strategies of CPP gave reproducible but incomplete results due to poor binding of low concentrations of CPP and the insufficient recovery of multiple phosphorylated peptides [89]. Recently, a specific hydroxyapatite (HA)-based enrichment procedure has been developed for complex mixtures of phosphoprotein/CPP [90]. Salt such as calcium phosphate, also occurring in bone and tooth tissue in the HA form, with the formula [Ca10(PO4)6(OH)2], has been previously used to enrich bone proteins [91]. The phosphate groups of phosphoproteins interact with crystalline lattice Ca2+ [92] more strongly than do the carboxyl groups [93]. Moreover, increasing protein phosphorylation leads to tighter binding of the proteins/CPP to HA [92]. One might conclude that the affinity of the multi-phosphorylated proteins/peptides for HA is significantly higher than that of the same components with lower phosphorylation. Essentially, the HA-based protocol immobilizes on HA microgranules proteins/peptides through their phosphate groups, while the non phosphorylated components are washed out using various buffers. In a previous article, CPP immobilized on HA were progressively eluted, increasing phosphate in the elution buffer, and then identified by off-line MALDI-MS [94]. This procedure was accelerated, and loss during elution was minimized by spotting HA-CN/CPP microgranules onto a MALDI target and analyzing the peptides directly by MALDI-TOF [90]. This method was useful for measuring the phosphorylation level of phosphoproteins/CPP quickly, with less than 2 h elapsing from the fractionation of the protein/CPP to the readout of the MALDI spectra (excluding the trypsinolysis step).
The more important advantages of the procedure are the possibility of (1) detecting phosphorylated proteins/peptides even in complex mixtures, (2) determining phosphorylated sites and those dephosphorylated by phosphatase, (3) attaining information regarding weakly and heavily phosphorylated peptides and (4) adding the HA-CPP complex directly to food, which is enabled by the use of an edible resin such HA [90]. Moreover, use of available commercial CPP preparations by the food industry is difficult for three primary reasons: i) the matrix bound to CPP is often not edible and such products can be hazardous; ii) the preparation of CPP is a long and a laborious procedure that requires cumbersome and expensive manipulation; and iii) CPP have an unpleasant taste even in modest amounts, which disadvantageously limits their direct utilization as a human food ingredient. A novel HA-based method for food grade CPP preparation has been performed on tryptic digests of casein. HA captured all CPP free of non-CPP [90]. There were approximately 32 HA bound CPP, and all non-CPP peptides were eluted [90]. HA-based enrichment procedure has been successfully applied to phosphopeptide recovery from complex biological fluids such as human serum thus providing a great source of potential biomarkers of disease. Four primary phosphopeptides derived from fibrinogen were enriched from human serum (Figure 3a-b, Table 4). A similar set of phosphorylated peptides was previously obtained using a modified IMAC strategy coupled to iterative mass spectrometry-based scanning techniques [95], using the titanium ion-immobilized mesoporous silica particles and MALDI-TOF [96] and cerium ion-chelated magnetic silica microspheres [97].
MALDI-MS-TOF spectra for the human serum before (a) and after (b) enrichment by HA (insert is the zoomed between 700 and 3000 Da).
Fibrinopeptide A (FPA) (f1-16)1P, (SerP3), a 16-residue long peptide (1615 Da) (Table 4), is the segment anchored on the thrombin surface [98]. The other three phosphopeptides, (f1-15)1P, (f2-15)1P and (f2-16)1P (Table 4), are hydrolytic products of FPA. The serum level of fibrinogen and its hydrolytic products may reflect the expression and activation of enzymes including kinase, phosphatase, and protease [99]. An altered ratio of FPA (f2-15) and FPA (f1-16) is detected in patients affected by hepatocellular carcinoma; the D2[pS]GEGDFLAEGGGV15 peptide is upregulated, and the A1D[pS]GEGDFLAEGGGVR16 peptide is down-regulated greatly. The other two peptides, A1D[pS]GEGDFLAEGGGV15 and D2[pS]GEGDFLAEGGGVR16, varied only slightly between the two groups [96]. The proportions of fibrinogen and their phosphorylation products offer new opportunities for basic research in exploring new frontiers in bio-marker discovery.
Identification of phosphorylated fibrinogen fragments from human serum immobilized on HA.
Because of the lower value, the addition of UHT and milk powder to raw or pasteurized milk is prohibited (EU Directives 92/46 CEE and 94/71 CEE) for cheese milk. The intensity of heat treatment was found to correlate with the furosine content. Glycated proteins and peptides formed during the initial stages of the Maillard reaction are indirectly evaluated through the furosine content [100-101]. The Amadori compound formed upon the reaction of lysine residue with a lactose molecule will prevent the digestive enzymes from reaching the binding sites. Native and lactosylated forms of β-CN (f1-28)4P, (f1-27)4P and αs2-CN (f1-24)4P, although typical of UHT milk and milk powder, are missing in raw, pasteurized milk (71.7 °C for 15 s) and intensely pasteurized milk. The lactosylated peptides that varied with heat treatment characterize UHT milk added in amounts not lower than 10% to raw and pasteurized milk [102]. Milk delactosed with microbial β-galactosidase did not suppress the Maillard reaction; indeed, the furosine concentration increased to 35-400 mg/100 g of protein [103]. As expected, a lactose-reduced UHT milk had β-CN (f1-28)4P glycated mainly by its monosaccharides (Figure 4a).
Therefore, the nonenzymatically glycated CPP derived from the reaction of one molecule of glucose or galactose with a lysine residue (m/z 3641) can be considered to be the signature peptide of lactose-reduced milk (Figure 4).
Enlarged view of the MALDI spectrum of β-CN (f1-28)4P (MH+ = 3479 Da) signature glycosylated CPP in lactose-reduced UHT milk (a) and lactosylated CPP in UHT milk (b). The mass differences corresponded to lactose and glucose/galactose residues.
Yogurt is a fermented milk defined as the “food produced by culturing one or more of the optional dairy ingredients (cream, milk, partially skimmed milk, and skim milk) with a characteristic bacteria culture that contains the lactic acid-producing bacteria, Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus”. A heat treatment of 90 °C for 10 min is considered optimal to obtain a good quality yogurt [104], and the addition of milk powder increases the content of furosine to more than 300 mg/100 g protein [105]. In yogurt, enzymes could give rise to the liberation of a particularly high number of bioactive peptides, among them CPP, which could be partly due to LAB proteolytic activity. Comparison of CPP in raw, pasteurized and intensely heated milks has previously shown that there is a plethora of milk peptides among which a few were glycosylated CPP [102]. Yogurt is prepared from intensely heated milk instead of low-pasteurized drinking milk. The CPP of two preparations were enriched on HA and analyzed by MALDI-TOF (Table 5). The proportion of CPP with molecular masses between 2.5 and 4 kDa was significantly higher in yogurt than in pasteurized milk as shown in Table 5. Only four fragments of CPP-derived peptides produced during yogurt preparation occur in pasteurized milk (Table 5).
List of HA-enriched CPP identified in commercial samples of yogurt and pasteurized milk. Relative intensity of each peak is reported.
For example, β-CN (f1-28)4P, a peptide representing 100% intensity (assumed as base peak) of the signals in MALDI spectra, was reduced by approximately 30%; this loss was associated with the transformation of pasteurized milk into yogurt. One can deduce that the original peptide undergoes degradation even considering the higher number of formed CN peptides. In yogurt, β-CN (f1-28)4P, the most common CPP in pasteurized milk, was hydrolyzed into the peptide β-CN (f15-28)4P, which thus becomes the most abundant CPP.
β-CN (f1-29)4P, β-CN (f1-28)4P, β-CN (f1-25)4P, β-CN (f1-24)4P, αs2-CN (f1-24)4P, αs2-CN (f1-21)4P, resulting from the CN hydrolysis by plasmin and enriched on HA, were also found as C-terminally shortened peptides. During fermentation and storage, αs2-CN (f115-150)3P and αs2-CN (f115-149)3P derived by plasmin action did not react further to produce shorter peptides, most likely because of the absence of proteolytic enzymes. In the yogurt fraction recovered by centrifugation, only five multi-phosphorylated αs1-CN and two low-phosphorylated κ-CN, κ-CN (f106-163)1P and κ-CN (f106-169)1P, were identified. Few CPP were less phosphorylated than the native peptides due to the presence of milk phosphatase, which was denatured in all pasteurized cheese-milks. The presence of lactosylated β-CN (f1-28)4P CPP was indicative of yogurt made with high-heat treated or milk fortified with milk protein powder [102]. Proteolysis of milk proteins in model yogurt systems has shown a similar set of primary CPP (Table 5). Therefore, the question is raised how CPP, derived from the enzymatic hydrolysis of yogurt CN are digested and absorbed in adult humans. For this reason, it is important to know the gastrointestinal resistance of CPP if used as a functional ingredient for fruit beverages. In the various stages of human digestion, a large quantity of CPP is produced in the stomach by partial hydrolysis of CN through pepsin action and in the small intestine by trypsin; these peptides are successively refined by endoproteases/exopeptidases. Although analysis of the intestinal contents of milk and yogurt ingestion has revealed the presence of CPP [60], their further resistance to gastrointestinal enzymes is poorly documented. Fragment β-CN (f1-24)4P has been previously identified in the lumen contents of rats after 60 min of digestion as a β-CN (f1-25)4P derived peptide [106]. Moreover, after yogurt ingestion, β-CN (f1-32)4P CPP was released in the human stomach [60] and β-CN (f1-31)4P was found in a yogurt sample. The fragment β-CN (f1-28)4P constitutes a clear example of the multi-functionality of milk-derived peptides because some regions in the primary structure of caseins contain overlapping peptide sequences that exert different biological effects, in this case both mineral binding and immunostimulatory action [107]. Even with the difference in the peptide pattern, it is evident that CPP binding iron (or other metal ions) remains soluble in the digestive tract, where they escape further enzyme digestion [106]. The authors have studied in depth the simulated digestion of CPP from peptide precursors. These studies greatly benefit from the knowledge of enzyme specificities and degradation mechanisms. CPase and chymotryptic activity of pancreatin exhibits broad specificity, cleaving bonds on the carboxyl side of several amino acid residues of CPP. The latter, which are in the mass range 960-7087 Da (Table 5), are good candidates for intestinal absorption and for playing a possible physiological role in mineral bioavailability. However, there are conflicting results on the lack of αs1-CN (f43-52)2P and αs2-CN (f1-19)4P identified by other authors after CN hydrolysis with pancreatin, an enzyme used during the intestinal step of simulated physiological digestion [108]. Generally, the physiological effects of CPP may not always be extended to precursor peptides, although they are structurally similar. There are not enough data concerning the effects of CPP addition to probiotic acid fermented milks. However, probiotic bacteria such as Lactobacillus acidophilus and Bifidobacterium spp., selected because of their beneficial action, which they may manifest on the health of the consumer, grow slowly in milk because of the lack of the proteolytic activity [109]. For this reason, and also to reduce the fermentation time, probiotic yogurt is manufactured by yogurt bacteria (Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus) with the addition of probiotic culture. In parallel, non-digestible food ingredients, i.e., “prebiotics”, resist digestion in the small intestine and reach the colon, where they act as a growth factor for Bifidobacterium species and are metabolized into short chain fatty acids by a limited number of the microorganisms also comprising the colonic microflora. Prebiotics are principally oligosaccharides (fructo-oligosaccharides, inulins, isomalto-oligosaccharides, lactilol, lactosucrose, lactulose, pyrodextrins, soy oligosaccharides, transgalacto-oligosaccharides, and xylo-oligosaccharides) that stimulate bifidobacteria growth. In probiotic yogurt containing inulin as a prebiotic, the number of bioactive peptides increased, which means that elevation in the proteolytic activity has a synergistic effect with probiotic counts of yogurt cultures. Therefore, the most proteolytic strains of St. thermophilus and Lb. delbrueckii subsp. bulgaricus, spp. enhance the growth of Lb. acidophilus and Bifidobacterium. In our studies, the overall opiate activity of the bio-yogurt preparation containing Lb. acidophilus and Bifidobacterium spp. and inulin as a prebiotic was approximately twice that typical of traditional yogurt. In addition, the above yogurt preparation contained a variety of opioid agonistic and antagonistic, immunomodulation, anti-thrombotic, ACE-inhibitor, and anti-microbial activities. Traditional and probiotic yogurt both possess a characteristic soluble fraction composed by peptides exhibiting biological activity, amongst others. This fraction was found to include CPP, β-casomorphins and antithrombotic peptide precursors that did not differ greatly from one another. In a study comparing the proteolytic, amino-, di-, tri- and endopeptidase activity of nine strains of St. thermophilus, six strains of Lb. delbrueckii, fourteen strains of Lb. acidophilus and thirteen strains of Bifidobacterium spp., aminopeptidase activity was detected for all bacterial strains – traditional yogurt strains and probiotic bifidobacteria - both at the extracellular and intracellular levels. High dipeptidase activity was demonstrated by all bacterial strains for Lb. delbrueckii ssp. bulgaricus, Lb. acidophilus, and Bifidobacterium spp., whereas St. thermophilus had greater dipeptidase activity at the extracellular level.
Whole milk contains a variety of endogenous plasmin-mediated CN peptides. In addition, CPP were released following cell lysis and release of intracellular LAB enzymes. This phenomenon was observed especially at the end of ripening in long-ripened cheeses, such as Comté [110], Grana Padano [111], Parmigiano-Reggiano and semi-hard Herrgard cheese [112]. In Grana Padano cheese, 45 CPP were identified, of which 24 originated from β-casein, 16 from αs1-casein and 5 from αs2-casein. These CPP formally derive from three parent peptides, namely β-CN (f7-28)4P, αs1-CN (f61-79)4P and αs2-CN (f7-21)4P [111]. By comparing CPP of Grana Padano and Herrgard cheese, it was clear that CPP were all progressively shortened and dephosphorylated during ripening. CPP were very resistant to enzymatic degradation, especially when SerP residue was at the N-terminal end. The number of CPP identified according to the different procedures was comparable for Grana Padano [111] and Herrgard cheese [112]. In both the cheeses, CPP were progressively shortened and dephosphorylated during ripening, with both cheeses constituting heterogeneous mixtures of peptides phosphorylated at various sites sharing N- and C-terminally truncated CPP. However, some peptides proved very resistant to enzymatic degradation, especially when SerP residue was present at the N-terminal end of CPP [111]. The only SerP residue located at the N-terminus of CPP was subjected to dephosphorylation, exposing the dephosphorylated residue to aminopeptidase action. A heterogeneous CPP pattern also differentiated the cheese samples within a given form because of the phosphatase gradient amongst peripheral and central parts of the Grana Padano cheese form (3 105\n\t\t\t\t\tvs. 3 102). This is due to heat sensitivity in the temperature range 57 and 62 °C and the acid pH at which these enzymes are denatured. These data explain the discrepancy in the amount of serine, which varied by as much as 50% of SerP from the periphery towards the center of the cheese form [113]. In contrast, the CPP fraction of Herrgard cheese was more uniform, with the two cheese varieties sharing active plasmin and amino-peptidases from lactic acid bacteria. Because milk pasteurization denatures alkaline phosphatase while it activates plasmin [114], proteolysis in the above cheese is plasmin-dependent. It is therefore likely that CPP of pasteurized milk cheeses are intrinsically more stable than raw milk cheeses [111]. CPP in artisanal PDO ovine Fiore Sardo cheese have been previously reported [115]. Patterns of CPP similar to that observed for bovine cheese indicated that mechanisms of formation and degradation of CPP were similar regardless of the milk species and cheese variety. The dephosphorylation mechanism in Fiore Sardo was different from that found in Grana Padano cheese, most likely because of the use of different rennet types. In PDO Fiore Sardo cheese, no apparent difference in susceptibility to dephosphorylation was found amongst the differently located SerP peptide residues. This resulted in the simultaneous occurrence of partly dephosphorylated peptides, either internally or externally. CPP enrichment by HA, for example of pH 4.6 soluble fractions of hard Parmigiano Reggiano (PR) (30-mo-old), semi-hard, pasta filata Provolone del Monaco (PM) (6-mo-old), semi-cooked Asiago d’Allevo (AA) (3-mo-old) and mold-ripened cheese Gorgonzola (GR) (2-mo-old) cheese, has allowed the identification of CPP in high number (Figure 5) which may explain the broad-specificity of the cheese enzymes involved in CN proteolysis. Some CPP were derived from the Lys-X or Arg-X cleavage by plasmin primarily located in the N-terminal region of caseins, such as β-CN (f1-28)4P (Lys28-Lys29) or β-CN (f1-29)4P (Lys29-Ile30), αs1-CN (f61-79)5P (Lys79-His80) and αs2-CN (f1-24)4P (Lys24-Asn25). The native plasmin-derived CPP were then further hydrolyzed by cheese aminopeptidases and CPase into shorter peptides.
It is likely that ingested cheese carries a concentrated pH 4.6 soluble CPP fraction and a variable number of CPP according to the cheese variety. Above all, the presence and integrity of plasmin-mediated products of CN is a function of the milk, whether raw or pasteurized. Pasteurization reduces the milk plasmin activity only by ~15 percent, whereas plasmin activity increases during milk storage. UHT does not inactivate the plasmin in milk, and proteolytic activity will continue to damage milk. Heat treatments modify the peptide profile by increasing the content of larger peptides. The CN breakdown occurring during the ripening of PR cheese proceeded more slowly in PM cheese.. This means that eating PR cheese increases the quota of the co-ingested mineral bound CPP. In contrast, GR cheese show a different CPP level such as that of β-CN (f1-27)4P (3350.2 Da), resulting the most abundant CPP, when compared with hard cheeses (Figure 5a and 6); β-CN (f1-27)4P was further hydrolyzed into the shorter β-CN (f7-27)4P (2580.4 Da), β-CN (f10-27)4P (2270.0 Da), β- CN (f12-27)4P (2083.8 Da) and β-CN (f15-27)4 (1742.4 Da). The most abundant CPP in all three cheeses derived from the peptide β-CN (f1-28)4P, but long-ripened PR cheese was dissimilar from the other cheeses in its content of αs1-CN (f62-79)5P (2332.9 Da) (Figure 5d and 6).
The MALDI spectra of CPP isolated by the addition of HA to pH 4.6 soluble fractions of Gorgonzola (a), Asiago (b), Provolone del Monaco (c), and Parmigiano Reggiano (d) cheeses. The inset magnifies the m/z values in the lower molecular mass peptide range 0.8-4 kDa.
Histogram representation of CPP at 100% relative intensity and their performance in four cheeses.
β-CN (f1-28)4P (3478.4 Da) in AA cheese was the most abundant signal of the MALDI spectra and it was partially hydrolyzed into the shorter peptides β-CN (f7-28)4P (2708.5 Da), β-CN (f15-28)4P (1869.7 Da) and β-CN (f17-28)3P (1589.6 Da) (Figure 5b and 6). Considering exclusively the CPP molecular mass in the 3-3.5 kDa range of AA and GR cheese, the intensity of a high number of peptides transformed into a number of progressively lower molecular weight CPP, with accompanying liberation of peptides (Figure 5). The most common group of CPP occurred in the mass range of 1.7-2.9, reaching the maximum intensity for β-CN (f12-28)4P (2212.0 Da) in PM and αs1-CN (f62-79)5P (2332.9 Da) in PR cheese (Figure 5c-d and 6). The presence of β-CN (f16-22)3P (977.7 Da) was discovered in both AA and PR cheeses and was not detected in the PM and GR cheeses (Figure 5). Our results show that longer plasmin-mediated peptides degraded into shorter CPP. These peptides became more evident when the chymosin retained in the cheese was largely inactivated by cooking the curd at high temperatures (~55 °C). The hydrolysis of CN by chymosin was covered by that of plasmin, which became the principal proteolytic enzyme in the cheese. This phenomenon is particularly evident in PM raw milk cheese for which the plasmin-mediated β-CN (f1-28)4P peptide, representing ~0.1% of the CPP, was almost completely hydrolyzed into the shorter peptides β-CN (f11-28)4P (2341.1 Da), β-CN (f12-28)4P (2212.0 Da), β-CN (f11-25)4P (1985.7 Da) and β-CN (f12-25)4P (1856.6 Da) (Figure 5c). When comparing the PR and PM cheese, the former had a high extent of β-CN (f1-28)4P as judged by the higher levels of the peptide. This demonstrates that CPP of PR cheese are progressively transformed into a number of lower-molecular-weight peptides. In contrast, the quasi-total absence in the PM cheese of β-CN (f1-28)4P and relatively few of the various sizes β-CN-derived CPP (Figure 6) could be the effect of the enzyme decline from the optimum level of activity to zero enzyme activity.
αs1-CN CPP originated for the greater parts from the internal regions of the amino acid sequence, namely αs1-CN (f61-79)5P and αs1-CN (f33-60)3P.
In PR cheese, 23 casein-derived CPP were found to derive from the internal region of αs1-CN, i.e., αs1-CN (f59-79)5P, whereas they were not detected in AA (Figure 7).
The number of CPP derived from αs1-CN (f59-79)5P and αs2-CN (f1-24)4P in Parmigiano Reggiano, Provolone del Monaco, Asiago and Gorgonzola cheeses.
Amino acid sequence of the αs1-CN (f59-79) 4P peptide and the CPP identified in PR cheese. Phosphoserine residues are indicated by red boxes.
The profile of the CPP depicts the mechanisms of both the proteolysis and dephosphorylation in a long ripened cheese. Peptide αs1-CN (f61-79)5P, most likely arising from the parent peptide αs1-CN (f1-79)7P through cleavage at Met60-Glu61, was dephosphorylated and concurrently hydrolyzed into shorter peptides. Alkaline and/or acid phosphatases acting on SerP residue dephosphorylated CPP. N-terminal Ser was then exposed to aminopeptidase and released as a free amino acid. Bacterial CPase or exopeptidase such as cathepsin D/chymosin release αs1-CN (f61-74)4P and other derived CPP through cleavage at Asn74-SerP75 (Figure 8). In PR aged 30 months, αs1-CN (f61-79)5P (2462.1 Da), αs1-CN (f62-79)5P (2332.9 Da), αs1-CN (f63-79)5P (2261.9 Da), αs1-CN (f64-79)5P (2132.8 Da), αs1-CN (f64-79)4P (2052.8 Da), αs1-CN (f65-79)4P (1965.7 Da), αs1-CN (f62-74)4P (1681.3 Da), αs1-CN (f64-74)4P (1481.2 Da), αs1-CN (f64-74)3P (1401.2 Da) and αs1-CN (f65-74)3P (1314.1 Da) were the dominant CPP (Figure 5d and 8). Indeed, only 7 CPP for PM cheese and 11 CPP for GR were derived from αs1-CN (f59-79)5P, namely αs1-CN (f61-79)5P (2462.1 Da) and αs1-CN (f61-74)4P (1810.5 Da) (Figure 5a and c and 7). Considering the αs2-CN peptide, the αs2-CN (f1-24)4P CPP were similar in number but significantly different in the case of the four cheese varieties (Figure 6). The dominant αs2-CN-derived CPP were αs2-CN (f1-24)4P (3132.9 Da) and αs2-CN (f1-21)4P (2747.6 Da) in AA cheese (Figure 5b). The most abundant αs2-CN-derived CPP were αs2-CN (f1-18)4P (2355.1 Da) for PM and αs2-CN (f6-18)4P (1751.4 Da), a shortened form of the primary CPP αs2-CN (f1-18)4P, for GR cheese (Figure 5a and c). αs2-CN (f7-18)4P (1614.3 Da) and αs2-CN (f8-18)4P (1515.1 Da) characteristically accumulated in PR cheese (Figure 5d). Similar and discrete phosphorylated CPP derived species for αs2-CN (f1-24) (3P and 4P) and β-CN (f1-28) (3P and 4P) occurred in all cheeses. For the other casein fractions, primary CPP are fully phosphorylated, such as αs1-CN (f61-79)5P, whereas the derived peptides show a level of phosphorylation less than native form as observed in PM and GR. A higher dephosphorylation level characterized the CPP profile of PR cheese (Figure 8). The different profile of CPP could derive from the different length of ripening and from the cheese variety.
Cheeses that contain CPP are also manufactured from ovine milk. Proteolytic enzymes in Pecorino cheese originate from chymosin, pepsin and other clotting preparations such as paste rennet. These enzymatic activities are complemented by those secreted by the vegetative spores of Penicillium roqueforti during the maturation of blue-veined cheeses. The CPP patterns of Pecorino and Roquefort cheese have been characterized and main components identified. The sequence alignment of the CPP released throughout the hydrolysis of the β-CN (f1-28)4P in Pecorino and Roquefort cheeses are compared in Figure 9.
In PR cheese of different ages, the released CPP were progressively degraded at C- and N-terminal ends. CPases work from the C-terminal end and aminopeptidases from the N-terminal end, both removing the terminal amino acid residues incrementally. LAB does not produce CPases; thus, the ability to liberate the carboxyterminal amino acid and peptides is typical of the mold. The N-terminal amino acid seemed to be released faster than the C-terminal residues because of the lower activity of CPases. There are negligible differences in the CPP level of different cheese lots primarily because of the action of the enzymes from P. roqueforti after its sporulation in blue-veined cheese. More long-chain CPP β-CN, such as β-CN (f1-28)5P-4P, β-CN (f1-27)5P-4P and β-CN (f1-24)5P-4P, were detected in Pecorino cheese, whereas β-CN (f7-28)5P-4P and β-CN (f7-27)5P-4P resulted from the longer CPP in Roquefort cheese (Figure 9). In these cheese varieties, both αs1- and β-CN have been described as completely hydrolyzed at the end of ripening. This contradicts other findings indicating ~50% CN hydrolysis. Plasmin, NSLAB, and Lactobacilli contaminating flora proteinases are mainly responsible for extensive proteolysis in Parmigiano-Reggiano cheese, which is ripened for ~24 months at ~18-20 °C [116]. Here, chymosin is denatured by the high cooking temperature used during the manufacture of cheese. Molds develop at approximately 2 to 5 weeks of ripening, concurrently degrading CN into peptides of various sizes [117]. A similar mechanism for β-CN-derived CPP was found in Grana Padano cheese. Ser was proteolytically cleaved by aminopeptidases, and SerP hindered cleavage by the latter and continued its action after dephosphorylatation of SerP.
Amino acid sequence of the β-CN (f1-28)4P peptide and the CPP identified in Pecorino (blue line) and Roquefort (yellow line) cheeses. CPP common to the two cheeses are indicated by crosses, and phosphoserine residues are indicated by red boxes.
Due to proteolytic activity, a great number of CPP are formed in raw milk cheese. In contrast, the enzymatic digestion of proteins to peptides can be reduced by milk pasteurization. Notwithstanding this, yogurt remains a consistent source of bioavailable CPP even if milk is heated to high temperatures (90 °C, 30 min) to create an inoculation medium in which the bacteria can grow and produce lactic acid. LAB provide plenty of CPP in the form of soluble complexes with Ca2+ that are effective in avoiding the life-threatening calcium phosphate precipitation, enhancing the intestinal absorption of minerals and retention in the human body [34,118]. The mineral-binding power of CPP also depends on the number of binding sites and their relative accessibility [119]. Dairy products such as cheese and yogurt are both rich in multi-phosphorylated peptides capable of interacting with colloidal calcium phosphate to manifest anticariogenic properties in human and animal [120-121,13]. The mechanism of anticariogenicity might be due to a direct chemical effect of casein and calcium phosphate components [122]. Tooth enamel is a polymeric substance consisting of crystalline calcium phosphate, embedded in a protein matrix. Thus, CPP can significantly enhance localization of ACP at the tooth surface, inhibiting enamel demineralization and promoting remineralization. In the development of teeth and bone, CPP act as hydroxyapatite nucleator and control the growth of the crystals, resulting in unique crystal morphology. A new calcium phosphate remineralization technology has been recently developed based on the complex CPP-ACP [RecaldentTM CASRN691364-49-5] [66]. This preparation is claimed to stabilize calcium and phosphate ions in high concentrations by binding ACP to pellicle and plaque of the tooth surface. Moreover, CPP-ACP inhibited the adhesion of Streptococcus mutans to the tooth surface producing a copious reservoir of bioavailable calcium ions [67]. Cheese and yogurt CPP have the ability to stabilize calcium phosphate in solution, forming small CPP-ACP nanocomplexes. The calcium-binding ability of CPP has been applied by clinical dentists to show that CPP stabilize high concentrations of calcium, phosphate, and fluoride ions on the tooth surface by binding them to pellicle and plaque [66,123]. In dental plaque, CPP-ACP binds onto the surface components of the intercellular plaque matrix. Incorporation of CPP-ACP into the plaque will increase the calcium and phosphate content by forming a stable supersaturated solution of calcium phosphate. Thus, the availability of calcium in plaque provides a natural anticaries protective effect, either by suppression of demineralization promoted by fermentative acids in mouth, through an increased remineralization by binding calcium ions to teeth enamel, or possibly a combination of both. An inverse relation between plaque calcium and caries incidence has been evidenced [124-125]. Reynolds (1997) [126] has demonstrated that CPP-ACP can actually remineralize subsurface lesions in human enamel, and this is indeed the basis of one claim of his patent [127]. The diffusion of available CPP-ACP in the mouth is controlled by two main factors: i) the molecular weight of the diffusing species, the square of which is inversely proportional to the diffusion coefficient; and ii) the binding characteristics of the diffusing species, which dictate how much CPP-ACP is free to diffuse at a given time [128]. At neutral pH, calcium diffusion is limited by the quantity of bound calcium, reducing the effective diffusion coefficient (De) and creating a measurable restricted effective diffusion coefficient (rDe), where rDe =De/(R + 1) and R is the ratio of bound to free calcium. A large number of potential binding sites for calcium can have significant effects on the calcium diffusion coefficient; this effect is maintained at low pH, although overall diffusion is slightly faster [129-130]. Conversely, one may infer that ACP may also bind to dental plaque and tooth enamel, thus having beneficial effects on teeth remineralization [67]. In addition, SerP residues of the CCP-HA complex are exposed to intestinal alkaline phosphatase, which favors metal ion bioavailability by releasing inorganic phosphate. Milk, ice cream, and cheese have been observed to lower the incidence of dental caries in rats [131]. Elderly people that eat cheese several times per week had a lower incidence of root surface caries development [132]. CPP of yogurt have been observed to have an inhibitory effect on demineralization and are able to promote remineralization of dental enamel [133]. Moreover, anticariogenic activity has also been reported for egg phosphopeptides (viz. phosvitin and phosphophorin) [134-135]. The heating process affects the bioavailability of CPP; for example, milk sterilization can induce dephosphorylation of phosphoseryl residues and dehydroalanine residue formation [136].
Some commercial products have been developed containing moderately hydrolyzed milk proteins as the sole protein source. Hypoallergenic formulas are based on partially or extensively hydrolyzed proteins. Both formulae are better tolerated by small premature infants than native cow milk protein. Ultrafiltered micellar casein and microfiltered whey protein concentrate are known to slow down the digestive process. Typical composition data of commercial phosphopeptide preparations (m/m) include 91.3% (TN x 6.47) or 94.8 (dry basis) protein, 16.0% CPP, and 6.0% free amino acids. Compared with the expected CPP composition, the commercial preparation contained ~5% undigested protein, ~30% peptides in the intermediate molecular mass 5000-20000 Da range, and ~48% of molecular mass in the 500-5000 Da range (Tatua, New Zealand). The preparation is generally very complex and dependent on the procedure used to perform casein hydrolysis. Therefore, commercial products can be considered to be an enriched-CCP preparation containing 16% CPP without specification of the peptide size and phosphorylation degree. Preliminary analysis performed by MALDI-TOF analysis indicated that the signal in the mass spectra originated exclusively from the β-CN digestion. The intensity of non-CPP such as β-CN (f191-209), β-CN (f184-209), β-CN (f177-209) and β-CN (f170-209) was sufficiently high to obscure other CN peptides (MALDI spectrum not shown). As reported above, a number of available techniques allow the separation of CPP and non-CPP. To reduce the large dynamic range of non-CPP, HA was used for CPP enrichment [90,94,102]. CPP included multiply phosphorylated peptides (up to 4 phosphorylation residues). CPP β-CN (f1-28)4P and 3P, β-CN (f1-25)4P, 3P and 2P and β-CN (f2-25)4P, 3P and 2P were found and may be indicative of the progressive CPP dephosphorylation (MALDI spectrum not shown). Interestingly, in addition to β-CN, the commercial CPP (Tatua, NZ) also displayed αs1- or αs2-CN-derived CPP, invisible or weakly visible before the sample was treated with HA (Table 6).
Finally, a method for reducing the complexity of peptide mixtures was the separation of non-CPP and CPP by trapping CPP on HA under neutral conditions. This could be the principle for an industrially based production of CPP.
CPP identified in a commercial CPP preparation (Tatua Co-operative Dairy Company Ltd) by tandem MS sequencing.
Starting from CN, the overall preparation process gave 16% CPP (Figure 10), less than the theoretical yield of 23% (Ytheor =22.8%), which means approximately 20% yield on the basis of weight, a yield higher than that obtained by other researchers [138-140]. In their production experiments, the authors obtained a CPP preparation as high as 18.8% degree of hydrolysis (DH).
Schematic representation of the process-scale isolation of tryptic CPP from caseinate, showing the protein flow through the process (source: [141]).
The example of 2000 L Na-caseinate solution containing 180 kg protein and 1 kg trypsin yielded 29 kg of calcium-enriched CPP, corresponding to a yield of ~16% (w/w) [141]. A variety of raw materials such as acid casein, sodium caseinate, and calcium caseinate, as well as skimmed raw milk, milk concentrate by ultrafiltration, pasteurized and UHT milk near the limit date for consumption, may be used as the substrate for CPP production. The optimal parameters for the hydrolysis with trypsin were 37 °C and pH between 7.5 and 8.5. The casein hydrolysate solution was roughly fractioned by ultrafiltration with appropriate membranes to obtain soluble CPP both in the “permeate” and “retentate”. Lower-molecular peptides/phosphopeptides occurred in the “permeate” and larger in the “retentate”. The diafiltrate containing the tryptic casein digest was loaded on the ion exchange resin, and the non-CPP flowed through and were recovered for further use, e.g., as substrate for bacterial culture. Bound CPP, free of non-CPP, are eluted using sodium hydroxide, e.g., 0.2 M, and conductivity and absorbance monitored at 280 nm. The eluate containing CPP is collected and then concentrated, typically by reverse osmosis. Peptides were pasteurized (85 °C, 15 s) and spray dried, yielding sodium enriched CPP (Na-CPP). In other cases, to obtain calcium-enriched CPP, the concentrate is added with CaCl2 in excess, diafiltered, and then CPP solution concentrated by reverse osmosis until the filtrate conductivity was negligible (less than 3 mS cm-1). The concentrate is spray dried, and the product is labeled as calcium-enriched CPP (Ca-CPP).
A Ca2+/ethanol selective precipitation procedure was used to produce a CPP and non-CPP concurrently from an alcalase digest of whole casein in which the traditional and new processes for CPP production were reported [142]. CN is trypsinized, and the pH of the solution is adjusted to 4.6 to separate the non-peptide material. The CPP-Ca2+ aggregation was induced by ethanol addition in the supernatant and recovered as precipitate for freeze drying. In the novel process, the step of non-peptide material removal was omitted, and non-CPP (CNPP) was recovered as supernatant for use in alimentary products. For casein, the use of alcalase, a cheap enzyme suitable for industrial application, for hydrolysis was suggested [142]. The CN hydrolysates were separated into the two types of peptides using combined treatment with CaCl2 and ethanol. CPP and non-CPP comprised components with molecular weight lower than 2509 Da and 2254 Da, respectively, as determined using size exclusion HPLC. A DH of 20% for the CN hydrolysate was achieved. At the end, the recovery of CPP reached 24%. The phosphorus component of CPP was 3.08%, and nitrogen recovery was approximately 76% [142]. CPP generally had an improved solubility and transparency even under acid conditions and could be used as ingredient for beverages such as sport drinks, soft drinks, health drinks, fermented products, vitamin concentrates, fruit or fruit fractions.
A method for the preparation of selected anticariogenic CPP comprised the steps of complete digestion of CN as soluble monovalent cation salt with a proteolytic enzyme: the addition of a mineral acid to the solution to adjust the pH to approximately 4.7; the removal of any produced precipitate; the addition of CaCl2 to a concentration of approximately 1.0% (w/v) to cause the aggregation of CPP; the separation of the aggregated CPP from the solution through a filter with a molecular weight exclusion limit within the range 10000 to 20000 while passing the bulk of the remaining CPP in solution; the diafiltration of the separated CPP with water through a filter; the concentration of the solution; and the drying the retentate [143]. Peptides not included in the aggregation were removed by ultrafiltration/diafiltration. By this means, anticariogenic CPP at purity greater than 90% were obtained [143]. CPP including calcium, magnesium or both salts (or zinc, ferric or other salts) are produced by submitting CN to proteolytic enzyme hydrolysis, ultrafiltering the resulting hydrolyzate to produce a permeate containing CPP, adding a bivalent cation salt to the peptides to form CPP aggregates, and separating by ultrafiltration the CPP aggregates and non-CPP [144]. When CPP salts need to be converted to free phosphopeptides, they can be restored by acidification with HCl; the solution is then diafiltered extensively through a 1000 molecular weight cut-off membrane to remove excess calcium chloride.
The CPP-salts complex can be added to different foods. A stable acidic beverage or other alimentary products can be obtained by digesting casein with trypsin, precipitating the insoluble components at acid pH, adjusting the pH of the obtained supernatant to approximately 6.0, then adding calcium chloride and ethanol to recover an acid-soluble calcium complex of CPP and the reaction product and adding them to a soft drink [145]. The acid-soluble calcium complex of CPP enhances calcium absorption from food because calcium may be absorbed by the body in the form of soluble calcium. Acid-soluble CPP is a mixture of αs1-, αs2- and β-CPP, forming essentially no turbidity in solution at pH of 3.0 or less, and having purity greater than 90%, molecular weights between approximately 2500 and 4600 Da, and the ability to solubilize at least 100 ppm calcium at a concentration of 0.5 mg/ml CPP. The acid-soluble CPP produced in vitro also have a solubilizing capability on iron. It is widely believed that iron must be solubilized for absorption through the small intestine. Accordingly, health may also be enhanced by the absorption of the soluble iron in the drink by the human body. Similarly, magnesium may be solubilized in a drink or edible product of this type [145]. Therefore, in addition to drinks, preparation of CPP with high negative charge could be used as additive for healthy foods or for dietetic or pharmaceutical compositions, as they are capable of increasing the in vivo absorption of calcium or other ions [146]. Another interesting invention relates to processes and the compositions that are useful to remineralize the teeth of mammals, particularly humans, and impart acid resistance thereto. These compositions included a gum base or carrier, sweetening agents, CPP-ACP preparation and food-grade acids [147]. Because many chewing gum and confectionery products usually contain acids, many consumers enjoying chewing gum and confectionery products ingest acids causing demineralization of the tooth surface. CPP-calcium phosphate complexes are known to have anticariogenic teeth strengthening effects that could be used address the problem of dissolution or demineralization of tooth enamel and the resultant formation of dental caries. Exogenous CPP-ACP preparations have also been added to milk in 2.0-5.0 g⁄L amounts to remineralize enamel subsurface lesions, which actually increased with respect to the control [148].
These inventions create functional foods with undoubted beneficial effects on human health, possibly promoting recalcification of bones, protecting the tooth enamel from decay and other possible health benefits.
Proteins are no longer considered merely nutritional components because they possess encrypted peptides with possible biological properties [149-153]. The cited literature has highlighted that bioactive peptides may be released in vitro or in vivo by digestive and bacterial enzymes starting from casein or generally inactive precursors [151,154-155]. We have examined the case of casein-derived phosphopeptides that can be applied as dietary supplements in “functional foods” and produced on an industrial scale. With this, it has been demonstrated that, each time a health-enhancing nutraceutical is required for a functional food, an appropriate enzymatic hydrolysis of casein needs to be designed [156-157]. In addition to the anticariogenic activity, the most important function displayed by CPP is that soluble and encrypted casein phosphopeptides can arrive without modification of the phosphorylated sequence to the brush border membrane. It is postulated that short-sequence peptides reach their putative receptors in many tissues without modification. Whether they enter blood circulation or whether their action is restricted to a peripheral circle are current questions that await response. In conclusion, this review has considered milk and cheese CPP for specific food ingredients. The contribution of in vitro casein digests by gastric proteases to potential biologically active substances in the intestine must be simultaneously considered. Scientists are currently involved in investigations to define the in vivo fate of all of the bioactive peptides. The in vitro studies have allowed the scientists to compare the predicted and the experimental sequence of CPP. This step is preliminary to the clinical investigations designed to determine the bioactivity of the milk hydrolysates. These findings open an industrial perspective that will permit the unrestricted use of CPP in healthy promoting food application.
Publication in partial fulfilment of the requirements for PhD in Sciences and Technologies of Food Productions - XXV Cycle, University of Naples ‘Federico II’. The Authors gratefully acknowledge the American Journal Experts Association for the text revision (http://www.journalexperts.com/). This work was partly supported by the financial aid to C.L. from MIUR, Program PRIN-2008 HNHAT7-004.
An overwhelming majority of transport vehicles are driven by internal combustion (IC) engines which use fossil fuels as the propellant. Fossil fuel used in vehicles is known to be one cause of environmental degradation. The global need to stem environmental degradation, climaxed at the 2015 United Nations Climate Change Conference, COP 21/CMP 11 held in Paris, France. The Conference came up with the target of limiting global warming to below 2°C. This tells us that additional and more stringent measures are likely to be imposed on fossil fuels in the future. This will negatively impact on the use of internal combustion (IC) engines in vehicles. Even now, new targets on fuel economy are being set: ‘by 2021, new cars in Europe should emit no more than 95 g/km of CO2, representing a reduction of 40% compared with the fleet average of 158.7 g/km in 2007. At the same time, CAFÉ regulations in the US will require light vehicles to achieve 54.5 mpg (23.2 km/l) by 2025. These developments make manufacturing costs more important than ever. With approximately 87 million vehicles sold in 2015 and this number expected to rise to 115 million by 2030, introducing lightweight materials and innovative processes will enable car manufacturers to meet these ambitious targets’ [1].
\nOne method used by the automobile industry to tackle this challenge posed by new emission regulations is for IC engines to burn fuel more efficiently. Lightweighting, which is building lighter vehicles, is used to have better fuel efficiency [2]
The main purpose of lightweighting vehicles is to increase fuel efficiency [3]. For example, while a conventional gasoline car weighing about 750 kg may have a fuel economy of 22 km/l, a Shell eco-marathon [4] urban-concept gasoline vehicle weighing about 45 kg may have a fuel efficiency of over 400 km/l. This vividly shows the benefit of weight reduction on fuel economy.
\nOther reasons for lightweighting include:
To achieve better vehicle performance to give better acceleration, braking and handling.
To have greater load-carrying capacity to engine power ratio.
The methods of automobile lightweighting include:
The use of lighter materials such as high-strength steel, aluminium, magnesium, lightweight composites and plastics [5].
The use of optimum structural designs such as boxlike geometries to achieve greater rigidity to weight ratio. Figure 1 shows a car bumper with stacked-joined hexagonal lightweight pipes [6].
The use of hot-forming techniques including hot-stamping to produce ultra-high strength parts such as used for reinforcements for vehicle doors, bumper beams, etc., which can reduce weight to the tune of 50% compared to cold-formed parts [1].
‘Body-in-white’ (BIW) technique in which the unpainted metal components are welded together to form the vehicle’s body, which can account for approximately 50% of weight saving [1].
The use of stacked-joined hexagonal lightweight pipes for a car bumper [6].
Table 1 shows the major types of lightweighting materials used in the automotive industry [7]. It shows that weight reduction could be as high as 70% when carbon fibre composites and magnesium are used to replace mild steel.
\nLightweighting material | \nMass reduction with respect to mild steel | \n
---|---|
Carbon fibre composites | \n50–70% | \n
Magnesium | \n30–70% | \n
Aluminium and its matrix composites | \n30–60% | \n
Titanium | \n40–55% | \n
Glass fibre composites | \n25–35% | \n
Advanced high-strength steel | \n15–25% | \n
High-strength steel | \n10–28% | \n
Comparison of different lightweighting materials (Adapted from [7]).
Lightweight engineering materials require high strength, long life, high wear and corrosion resistance. In the current drive for cleaner energy use, the application of lightweight materials in internal combustion engines becomes imperative as it makes for greater fuel efficiency which results in pollution reduction. Unfortunately, there are no naturally occurring engineering materials that perfectly possess all these properties at the same time. To achieve some of these qualities in a single engineering material, dissimilar materials with unique characteristics can be made together as alloys or composite materials to produce improved performance characteristics. ‘Such fabricated composite materials find very wide application [8] in electronics, sporting goods, aerospace parts, consumer goods, marine and oil industries, automobile components like IC engine parts, etc. because of the high requirements in product performance and rise in global market demand of lightweight components’ [9].
\nMaterial selection for IC engine components has been one active area of research. Proper selection of materials for the production of IC engines is critical because of the high temperature and fatigue stresses the engine is subjected to. In selecting a suitable material for IC engine components, important parameters or factors such as the physical properties (i.e. melting temperature, hardness, creep and flow, corrosion, weight and vibration absorption) and mechanical properties (i.e. strength, strain, elastic modulus, ultimate tensile strength, yield strength, elongation, fatigue strength, pressure tightness and machinability) as well as availability and cost of the materials must be considered.
\nPalm kernel and periwinkle are common sources of foods and are harvested and processed in very large quantities in most parts of Southern Nigeria. However, their shells are disposed of indiscriminately giving rise to environmental challenges to communities where they are processed because palm kernel shell (PKS) and periwinkle shell (PS) do readily undergo biological degradation [10, 11].
\nAluminium and magnesium alloys are commonly used as lightweight engineering materials, and they are gradually taking over from cast iron and steel in the automobile and aerospace industries and defence applications [12, 13]. To improve the properties of aluminium, they are usually alloyed with other very expensive elements like chromium, nickel, molybdenum, silicon, boron, vanadium, etc. However, these alloying metallic elements are expensive and difficult to source in most parts of the developing world such as Nigeria. This study is directed at exploring alternative substitute materials for production of metal matrix composites (MMC) that can be suitable for the production of automobile parts [14]. Thus, the purpose of the study is to develop a hybrid composite material with PKS and PS as the reinforcement particles in aluminium matrix, for the production of appropriate IC engine parts. In this work, the engine block is used as case study because it is particularly important in that it houses the power-producing chamber and forms the fixed point for all other members of the engine. It is hoped that this could be a cheaper alternative to existing aluminium alloy engine parts.
\nThe following materials were used:
\nCommercially pure aluminium pieces cut from an ingot with the composition shown in Table 2 was used.
\nMg | \nSi | \nMn | \nCu | \nZn | \nTi | \n
0.00118 | \n<0.03456 | \n0.00058 | \n<0.00035 | \n0.00058 | \n0.00438 | \n
Fe | \nNa | \nB | \nSn | \nPb | \nAl% | \n
<0.09775 | \n0.00118 | \n0.00024 | \n0.01160 | \n0.00116 | \n99.85 | \n
Chemical composition of the commercially pure aluminium.
Palm kernel shell, a common agro waste (Figure 2(a)), was collected from a palm oil processing factory in Uselu Community in Benin City, Nigeria. The PKS was washed thoroughly with detergent and spread in the sun to dry. The dry shell was pulverised into powder of particle size 425 μm. The PKS powder is shown in Figure 2(b). PKS is reported to have chemical properties which include 8.786% calcium oxide (CaO), 6.254% potassium oxide (K2O), 54.81% silicon oxide (SiO2), 6.108% magnesium oxide (MgO), 0.362% iron oxide, 11.40% alumina (Al2O3), 33% charcoal, 45% pyroligneous liquor and 22% combustible materials [15].
\nPalm kernel shell (PKS). (a) Broken shells and (b) 425 μm powder.
The periwinkle shell (Figure 3(a)), another agro waste belonging to the pozzolanic group, is available in large quantities in the estuaries and mangrove swamp forest of the South-South region of Nigeria [16]. A large quantity of PS was sourced from its dump site around New Benin Market in Benin City, Nigeria. The PS was soaked in a mixture of detergent and water for 24 h and later washed and spread in the sun to dry. The clean PS was then pulverised with an electrically driven crushing machine into a powder of particle size 75 μm as shown in Figure 3(b). PS is reported to have a chemical composition of calcium content of 8.25 × 103 mg/100 g, potassium content of 5.50 mg/100 g, sodium content of 5.30 mg/100 g and phosphorus content of 2.55 mg/100 g [16].
\nPeriwinkle shell. (a) Shells and (b) 75 μm powder.
The hybrid aluminium composite material used in this study was made up of appropriate percentages of commercially pure aluminium and particular percentages of PKS and PS [14, 17].
\nThe hybrid composite material of aluminium metal matrix using agro wastes of palm kernel shell (PKS) and periwinkle shell (PS) powder as the reinforcement agents was designed using the central composite design (CCD) of the response surface methodology (RSM). In order to aid homogenous mix of the reinforcement materials in the matrix, the hybrid composite was formulated and fabricated by stir casting [18, 19] process using a stir casting machine.
\nThe experimental design for the study was done to optimise operating conditions (i.e. factor levels of the input variables) of the fabricated composite with respect to the predicted response parameters. The CCD method was selected because it allows the addition of axial runs which in turn allows the quadratic terms to be incorporated into the model. Three input variables were used in the design: pure aluminium ingot, PKS and PS. A total of six response variables were investigated: wear rate (g/s), creep rate (% elongation/h), density (kg/m3), tensile strength (MPa), hardness (BHN) and melting temperature (°C). Figure 4 shows the computer interface of the preliminary experimental design using the CCD.
\nComputer interface of the preliminary design of experiment.
The commercially pure aluminium ingot was cut into smaller sizes. The smaller pieces of the ingots were soaked with detergent and hot water at 50°C for 10 h and then washed thoroughly with a hard brush and later rinsed in clean water. The ingots were dried at about 70°C for 1.5 hrs. A digital electronic scale with an accuracy of 0.01 g was used to weigh the ingots into the various percentage weights as obtained from the design of experiment using CCD of RSM.
\nThe crucible furnace was initially preheated to 100°C. The pure aluminium ingots that were measured for the different experimental specimen weights were preheated for about 1 h at a temperature of 450°C [20]. The PS and PKS reinforcement particles were also preheated to 250°C to remove moisture and oil contents [21]. For the first sample labelled A-1, aluminium ingot of 87.5 wt.% \n
The developed composite material was used as engineering material to produce the engine block of a bush cutting machine shown in Figure 5 in order to conduct practical application assessment on the material to ascertain its applicability in real-life situation. Performance test was carried out on the produced engine block.
\nThe bought-out bush cutting machine.
The engine block was produced by casting and thereafter machined. The material was initially cast into a box dimension of 80 mm \n
The engine block of the bush cutting machine.
The fabricated engine block and cylinder liner were assembled into the engine as shown in Figure 7. It was thereafter tested for 1 h. The temperature of the engine block was taken at 1 min intervals. This was repeated for the control cylinder block and liner. The bought-out bush cutting engine block was used as the control engine block.
\nProduced engine block in bush cutting machine.
Lightweighting and energy cost saving analyses were carried out on an existing gasoline engine used for powering a newly designed lightweight utility vehicle. The engine is rated at 7.1 kW at 5500 rpm with a maximum torque of 18.0 Nm at 3500 rpm. The new material was hypothetically used to replace the conventional materials used for the engine block, cylinder head, piston and connecting rod. The potential weight reduction of the engine was then determined. The potential cost saving in energy was also determined.
\nEbhojiaye et al. [17] developed the hybrid composite material of palm kernel shell (PKS) and periwinkle shell (PS) particles as reinforcements in pure aluminium matrix. The central composite design (CCD) of the response surface methodology (RSM) was used to carry out the design of experiment (DoE) as shown in Figure 4. Stir casting method was used to fabricate the specimens. The design of experiments by the CCD gave 20 runs (experimental samples) as shown in Table 3. The runs were replicated three times each, bringing the total number of runs to 60 for each of the six responses considered, and 360 specimens were fabricated in all. Three experimental values were obtained for each of the 120 runs for the wear rate, creep rate, density, tensile strength, hardness and melting temperature. The average values were determined and recorded. Control specimens with 100 wt.% pure aluminium matrix, 0 wt.% of PKS and PS reinforcement particles were prepared. The results showed that the reinforcement particles had significant improvement on mechanical properties of the pure aluminium as shown in Table 4 for hardness test of the various 20 fabricated composites and that of the control commercially pure aluminium.
\nStd. | \nRun | \nType | \nFactor 1 (aluminium, % wt) | \nFactor 2 (periwinkle shell, % wt) | \nFactor 2 (palm kernel shell, % wt) | \nResponse 1 (wear rate (g/s) 10−4) | \nResponse 2 (creep rate, % elongation/h) | \nResponse 3 (density, kg/m3) | \nResponse 4 (tensile strength, MPa) | \nResponse 5 (hardness BHN) | \nResponse 6 (melting temperature, °C) | \n
---|---|---|---|---|---|---|---|---|---|---|---|
15 | \n1 | \nCentre | \n82.16 | \n8.92 | \n8.92 | \nA1 | \nA2 | \nA3 | \nA4 | \nA5 | \nA6 | \n
16 | \n2 | \nCentre | \n82.16 | \n8.92 | \n8.92 | \nB1 | \nB2 | \nB3 | \nB4 | \nB5 | \nB6 | \n
17 | \n3 | \nCentre | \n82.16 | \n8.92 | \n8.92 | \nC1 | \nC2 | \nC3 | \nC4 | \nC5 | \nC6 | \n
18 | \n4 | \nCentre | \n82.16 | \n8.92 | \n8.92 | \nD1 | \nD2 | \nD3 | \nD4 | \nD5 | \nD6 | \n
19 | \n5 | \nCentre | \n82.16 | \n8.92 | \n8.92 | \nE1 | \nE2 | \nE3 | \nE4 | \nE5 | \nE6 | \n
20 | \n6 | \nCentre | \n82.16 | \n8.92 | \n8.92 | \nF1 | \nF2 | \nF3 | \nF4 | \nF5 | \nF6 | \n
9 | \n7 | \nAxial | \n79.76 | \n10.12 | \n10.12 | \nG1 | \nG2 | \nG3 | \nG4 | \nG5 | \nG6 | \n
10 | \n8 | \nAxial | \n84.04 | \n7.98 | \n7.98 | \nH1 | \nH2 | \nH3 | \nH4 | \nH5 | \nH6 | \n
11 | \n9 | \nAxial | \n85.95 | \n−4.72 | \n9.33 | \nI1 | \nI2 | \nI3 | \nI4 | \nI5 | \nI6 | \n
12 | \n10 | \nAxial | \n72.44 | \n19.70 | \n7.86 | \nJ1 | \nJ2 | \nJ3 | \nJ4 | \nJ5 | \nJ6 | \n
13 | \n11 | \nAxial | \n85.95 | \n9.33 | \n−4.72 | \nK1 | \nK2 | \nK3 | \nK4 | \nK5 | \nK6 | \n
14 | \n12 | \nAxial | \n72.44 | \n7.86 | \n19.70 | \nL1 | \nL2 | \nL3 | \nL4 | \nL5 | \nL6 | \n
1 | \n13 | \nFact | \n97.56 | \n1.22 | \n1.22 | \nM1 | \nM2 | \nM3 | \nM4 | \nM5 | \nM6 | \n
2 | \n14 | \nFact | \n97.93 | \n1.05 | \n1.05 | \nN1 | \nN2 | \nN3 | \nN4 | \nN5 | \nN6 | \n
3 | \n15 | \nFact | \n80.81 | \n18.18 | \n1.01 | \nO1 | \nO2 | \nO3 | \nO4 | \nO5 | \nO6 | \n
4 | \n16 | \nFact | \n83.33 | \n15.79 | \n0.88 | \nP1 | \nP2 | \nP3 | \nP4 | \nP5 | \nP6 | \n
5 | \n17 | \nFact | \n80.81 | \n1.01 | \n18.18 | \nQ1 | \nQ2 | \nQ3 | \nQ4 | \nQ5 | \nQ6 | \n
6 | \n18 | \nFact | \n83.33 | \n0.88 | \n15.79 | \nR1 | \nR2 | \nR3 | \nR4 | \nR5 | \nR6 | \n
7 | \n19 | \nFact | \n68.96 | \n15.52 | \n15.52 | \nS1 | \nS2 | \nS3 | \nS4 | \nS5 | \nS6 | \n
8 | \n20 | \nFact | \n72.52 | \n13.74 | \n13.74 | \nT1 | \nT2 | \nT3 | \nT4 | \nT5 | \nT6 | \n
Assigned letter codes to the response parameters.
Composite label | \nDiameter of indenter (D) mm | \nDiameter of indentation (d) mm | \nLoad (Kg) | \nBHN (HBS 10/1000) | \n
---|---|---|---|---|
A5 | \n10.00 | \n2.08 | \n1000 | \n291.08 | \n
B5 | \n10.00 | \n2.12 | \n1000 | \n280.07 | \n
C5 | \n10.00 | \n2.11 | \n1000 | \n282.77 | \n
D5 | \n10.00 | \n2.10 | \n1000 | \n285.49 | \n
E5 | \n10.00 | \n2.08 | \n1000 | \n291.08 | \n
F5 | \n10.00 | \n2.11 | \n1000 | \n282.77 | \n
G5 | \n10.00 | \n3.20 | \n1000 | \n121.07 | \n
H5 | \n10.00 | \n1.75 | \n1000 | \n412.54 | \n
I5 | \n10.00 | \n2.54 | \n1000 | \n194.12 | \n
J5 | \n10.00 | \n3.00 | \n1000 | \n138.00 | \n
K5 | \n10.00 | \n2.77 | \n1000 | \n162.69 | \n
L5 | \n10.00 | \n2.50 | \n1000 | \n200.48 | \n
M5 | \n10.00 | \n3.00 | \n1000 | \n138.00 | \n
N5 | \n10.00 | \n3.40 | \n1000 | \n106.86 | \n
O5 | \n10.00 | \n1.98 | \n1000 | \n321.56 | \n
P5 | \n10.00 | \n1.97 | \n1000 | \n342.86 | \n
Q5 | \n10.00 | \n2.05 | \n1000 | \n299.75 | \n
R5 | \n10.00 | \n2.13 | \n1000 | \n277.42 | \n
S5 | \n10.00 | \n2.05 | \n1000 | \n299.75 | \n
T5 | \n10.00 | \n2.50 | \n1000 | \n200.48 | \n
U5 | \n10.00 | \n2.78 | \n1000 | \n98.50 | \n
Results of hardness test of the fabricated composites and pure aluminium.
In optimising the results obtained for the six responses using the central composite design (CCD) of the response surface methodology (RSM), three of the responses [i.e. wear rate (y1), creep rate (y2) and density (y3)] were minimised, while the other three responses [i.e. tensile strength (y4), hardness (y5) and melting temperature (y6)] were maximised. The optimal equations obtained for the actual factors [commercially pure aluminium (A), periwinkle shell (B) and palm kernel shell (C)] for the six responses are shown in Eqs. (1)–(6).
Wear rate (\n
Creep rate (\n
Density (\n
Tensile strength (\n
Hardness (\n
Melting temperature (\n
The result of the RSM analysis gave an optimal blend ratio of 80.98 wt.% aluminium, 13.55 wt.% periwinkle shell and 5.47 wt.% palm kernel shell particles. This optimum blend ratio when used to produce an engineering composite material will have the following properties: wear rate of 0.62 × 10−4 g/s, creep rate of 19.09% elongation/h, density of 2598.62 kg/m3, tensile strength of 94.04 MPa, hardness of 278.83BHN and melting temperature of 935°C. This solution that was selected with the aid of the design expert software 7.01 has a desirability value of 97.3%.
\nTable 5 shows the comparison of the chemical compositions of the as-received commercially pure aluminium with the fabricated aluminium composite. The as-received composition was given by the manufacturer, while that of the fabricated composite was determined in our laboratory using the EPA Method 3050B (concentrated HCl, HNO3 and HClO4). The results show that all the elements detected in the as-received sample increased in the fabricated composite (except for the ones that were not detected: boron and tin), while the aluminium decreased in the fabricated composite. However, the elements, cadmium, calcium, chromium and potassium, were added into the fabricated composite. The increase of elements and additions could have come from the palm kernel shell (PKS) and periwinkle shell (PS) as seen from Sections 2.1.2 and 2.1.3, especially for the elements silicon, calcium, potassium, iron and sodium.
\nElement | \nAs-received | \nFabricated aluminium composite | \nRemark | \n
---|---|---|---|
Magnesium (Mg) | \n0.00118 | \n0.027 | \nIncreased | \n
Silicon (Si) | \n<0.03456 | \n0.28 | \nIncreased | \n
Manganese (Mn) | \n0.00058 | \n0.19 | \nIncreased | \n
Copper (Cu) | \n<0.00035 | \n0.02 | \nIncreased | \n
Zinc (Zn) | \n0.00058 | \n0.03 | \nIncreased | \n
Titanium (Ti) | \n0.00438 | \n— | \nNot detected | \n
Iron (Fe) | \n0.09775 | \n0.26 | \nIncreased | \n
Sodium (Na) | \n0.00118 | \n0.19 | \nIncreased | \n
Boron (B) | \n0.00024 | \n— | \nNot detected | \n
Tin (Sn) | \n0.0116 | \n— | \nNot detected | \n
Lead (Pb) | \n0.00116 | \n0.06 | \nIncreased | \n
Aluminium (Al) | \n99.85 | \n96.90 | \nDecreased | \n
Cadmium (Cd) | \n— | \n0.001 | \nAdded | \n
Calcium (Ca) | \n— | \n0.11 | \nAdded | \n
Chromium (Cr) | \n— | \n0.0001 | \nAdded | \n
Potassium (K) | \n— | \n0.16 | \nAdded | \n
Chemical compositions of the as-received and fabricated composite samples.
The optimum blend ratio obtained from the RSM analysis, when used to produce an engineering composite material, gave the properties as shown in Table 6. This is compared with properties of the control commercially pure aluminium tested under same conditions and those predicted by the RSM analysis. The table shows that there is improvement on properties of the fabricated aluminium composite over the control commercially pure aluminium. The creep rate, wear rate and density are reduced by 75.6, 78.2 and 3.4%, respectively, while the tensile strength, hardness and melting point are increased by 30.7, 184.8 and 31.4%, respectively. Except for density, these improvements are quite significant.
\nProperty | \nCommercially pure aluminium control | \nFormulated hybrid aluminium composite | \nOptimal solution values obtained from RSM (predicted values) | \nAs-used values of existing engine blocks | \n
---|---|---|---|---|
Creep rate (% elongation/h) | \n74.04 | \n18.04 | \n19.09 | \nNot available | \n
Wear rate (g/s) | \n2.61 × 10−4 | \n0.57 × 10−4 | \n0.62 × 10–4 | \nNot available | \n
Density (kg/m3) | \n2709.13 | \n2617.39 | \n2598.62 | \n2570–2830 | \n
Tensile strength (MPa) | \n73.99 | \n96.74 | \n94.04 | \n130–280 | \n
Hardness (BHN) | \n98.5 | \n280.49 | \n278.83 | \n80–137 | \n
Melting temperature (°C) | \n685 | \n900 | \n935 | \n645–710 | \n
Physical and mechanical properties of the formulated hybrid aluminium composite [14].
From the table, the values of the actual formulated hybrid aluminium composite and the values predicted from the RSM analysis are reasonably close, with all the absolute deviations of the predicted from the actual ones not greater than 10%. For example, the deviations are 5.8, 8.7, 0.7, 2.8, 0.6 and 3.9% for creep rate, wear rate, density, tensile strength, hardness and melting point, respectively.
\nValues of the above properties obtained from this research study (i.e. As-cast values) were compared with existing properties of aluminium alloys used for the production of engine block (i.e. As-used values). From Table 5, out of the six properties of the engine block examined, the book values of two of the As-used (or existing) engine block properties (i.e. wear rate and creep rate) were not readily available in the literature. However, the other four properties (i.e. density, tensile strength, hardness and melting temperature) were available [27, 28]. The value of density obtained in this study was found to be within an acceptable range with the book value. The value of tensile strength was below the range found in literature. However, it is hoped that with further research work, an appreciable tensile strength value which will fall within the range of values found in the literature would be obtained. The value of the composite material hardness (As-cast value) was found to be far above the range of values of As-used (or existing) engine block. This shows that besides production of IC engine blocks, the developed composite material could also be used for the production of other engineering components where material hardness is of utmost importance. Again, the melting temperature of the developed composite material was found to be far higher than the range of values for aluminium engine blocks (As-used values) as currently used. The developed composite material therefore could withstand the high temperatures that exist within the combustion chamber of IC engines.
\nThe fabricated engine block and cylinder liner were assembled into the engine and tested for 1 h. The temperature of the engine block was taken at 1 min intervals. This was repeated for the control cylinder block and liner. The initial temperatures (i.e. before the engine was switched on) of the control engine block and the produced engine block were recorded as 25.6°C (room temperature).
\nFigure 8 shows the temperature variations for each test. The fabricated engine block had a mean temperature of 151.7°C, while that for the control engine block was 156.9°C giving a deviation of 3.3% from the control value. The lower mean value of the fabricated engine block indicates that it may have a slightly lower heat dissipating ability than the control engine block.
\nTemperature reading of produced against control engine blocks.
This is expected as it is a fabricated material from aluminium, periwinkle shell and palm kernel shell, the last two being non-metallic materials with lower thermal conductivities. Heywood [29] stated that the combustion temperature within the combustion chamber of the IC engine is about 250°C. Despite this relatively lower heat dissipating ability, the developed hybrid composite material may still be regarded as a good heat conductor because within the first minute, it shot up the engine block temperature from the initial room temperature value of 25.6°C to about 80.7°C, showing an upsurge of 3.2 times the room temperature value. This is comparable to the 3.9 times for the control engine block. This heat conducting phenomenon is good for engine blocks so as to preserve their life span.
\nA gasoline engine rated at 7.1 kW at 5500 rpm generating a maximum torque of 18.0 Nm at 3500 rpm used to power a new lightweight utility vehicle is considered. Table 7 shows potential weight reductions if this new aluminium hybrid material were to be used as materials for the engine parts indicated, volume for volume. The table shows that:
The weight of the engine block is reduced by 63.03% if the new material were to replace the grey cast iron used.
The weights of the cylinder head, piston and connecting rod will be reduced by 1.93, 2.13 and 6.37%, respectively, if the new aluminium hybrid material were to replace the aluminium alloys indicated.
The weight reduction for the engine block, cylinder head, piston and connecting rod totalling 13.501 kg will be 48.37% if the new aluminium hybrid material were used to make these parts.
The weight reduction for the whole engine weighing 25.75 kg will be 25.36% if the new material were used to make the engine block, cylinder head, piston and connecting rod.
Engine part | \nMaterial | \nDensity (kg/m3) [30] | \nWeight (kg) | \nVolume (m3) | \nWeight of equivalent aluminium hybrid material (kg) (density = 2617 kg/m3) | \nWeight reduction | \n||
---|---|---|---|---|---|---|---|---|
(kg) | \n(%) (on individual parts) | \n(%) (on total parts) | \n||||||
Engine block | \nGrey cast iron | \n7079 | \n10.25 | \n0.001448 (1448cm3) | \n3.789 | \n6.461 | \n63.03 | \n— | \n
Aluminium alloy (A356) | \n2670 | \n(3.866) | \n0.001448 (1448cm3) | \n(3.789) | \n(0.077) | \n(1.99) | \n— | \n|
Cylinder head | \nAluminium alloy (A356) | \n2670 | \n3 | \n0.001124 (1124cm3) | \n2.942 | \n0.058 | \n1.93 | \n— | \n
Piston | \nAluminium alloy (A4032) | \n2690 | \n0.094 | \n0.000035 (35cm3) | \n0.092 | \n0.002 | \n2.13 | \n— | \n
Connecting rod | \nAluminium alloy (A7075) | \n2803 | \n0.157 | \n0.000056 (56cm3) | \n0.147 | \n0.010 | \n6.37 | \n— | \n
Total | \n— | \n— | \n13.501 (7.117) | \n— | \n6.970 (6.970) | \n6.531 (0.147) | \n— | \n48.37 (2.07) | \n
Whole engine | \n— | \n— | \n25.75 | \n— | \n— | \n6.531 | \n— | \n25.36 | \n
Potential lightweighting by the new aluminium hybrid material.
The table also shows the comparison of weight reductions if the conventional aluminium alloy A356 and the new hybrid aluminium material were to be used to make the engine block. As the new material has a slightly lower density, it produces a slightly greater weight reduction of 1.99% over the A356 aluminium alloy. When all the above parts are made with their conventional aluminium alloy materials, the weight reduction will be 2.07% when the new aluminium hybrid material is used for the indicated engine parts.
\nThese results show that lightweighting of the engine and consequently the vehicle powered by it will be achieved if this new aluminium hybrid material is used.
\nIt is envisaged that the use of this new material in manufacturing engines will not only lead to lightweighting but also energy saving. If we consider melting in an induction furnace, the energy consumption for melting cast iron ranges from 550 to 575 kWh/ton, while that for melting light and solid aluminium scraps ranges from 500 to 625 kWh/ton [31].
\nUsing the average values of the above energy ranges, we have that the:
Cost of energy required to melt the cast iron engine block in Table 7 = ((550 + 575 kWh)/2 × (10.25 kg/1000)) × $0.13/kWh = $0.75.
Cost of energy required to melt the aluminium hybrid engine block in Table 7 = ((500 + 625 kWh)/2 × (3.789 kg/1000)) × $0.13/kWh = $0.28, where $0.13/kWh is the cost of electricity.
The above shows that there could be an energy cost saving of 62.67% in melting which accounts for a significant part of the manufacturing cost, if the new aluminium hybrid material is used in place of cast iron in manufacturing the engine block.
\nThis fabricated aluminium composite seems to present an interesting material which requires further work: while its tensile strength is about 53% less than the mean value for the commercially as-used, its hardness and melting points are 159 and 33% more than the mean values for the commercially as-used, respectively. While its tensile strength may further be improved, it could find uses not only for engine blocks but also for other engine parts such as parts of the linkage mechanism in the combustion chamber and other non-engine applications. Also, there is the need to determine its porosity due to these non-metallic combustible materials used as reinforcements.
\nThe search for lightweighting materials for automobiles is a continuing process that opens up opportunities for development of new engineering materials. This work which is a part of this process has shown that agro wastes such as palm kernel shell (PKS) and periwinkle shell (PS) may be used as reinforcement materials for metal matrix composites giving good results for fabrication of some IC engine parts such as the engine block. This new material has the potential of lightweighting engines and giving significant energy cost saving in the manufacturing process. Due to the interesting properties it has, further work is necessary to determine additional and/or proper areas of application.
\nThe authors wish to thank the Shell Petroleum Development Company of Nigeria Limited (SPDC) for being part sponsors of this work through the Shell Professorial Chair in Lightweight Automobile Engine Development at the Federal University of Petroleum Resources, Effurun, Delta State, Nigeria. The authors also thank the Federal University of Petroleum Resources and the University of Benin, Nigeria, for their support for the project.
\nOur thanks also go to Dr. P.E. Amiolemhen, Department of Production Engineering, and Dr. E.G. Sadjere, Department of Mechanical Engineering, both of the University of Benin, Nigeria, who were part of the original work.
\nBook - collection of Works distributed in a book format, whose selection, coordination, preparation, and arrangement has been performed and published by IntechOpen, and in which the Work is included in its entirety in an unmodified form along with one or more other contributions, each constituting separate and independent sections, but together assembled into a collective whole.
",metaTitle:"Attribution Policy",metaDescription:"DEFINITION OF TERMS",metaKeywords:null,canonicalURL:"/page/attribution-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\\n\\nAttribution – appropriate credit for the used Work or book.
\\n\\nCreative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\\n\\nWith the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\\n\\nIn case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
\\n\\nAll rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\\n\\nA Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\\n\\nIn instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\\n\\nEvery single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\\n\\nIndividual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\\n\\nEvery single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\\n\\nIn the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\\n\\nIntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\\n\\nAll these rules apply to BOTH online and offline use.
\\n\\nParts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
\\n\\nAll the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
\\n\\nPolicy last updated: 2016-06-09
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\n\nAttribution – appropriate credit for the used Work or book.
\n\nCreative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\n\nWith the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\n\nIn case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
\n\nAll rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\n\nA Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\n\nIn instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\n\nEvery single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\n\nIndividual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\n\nEvery single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\n\nIn the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\n\nIntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\n\nAll these rules apply to BOTH online and offline use.
\n\nParts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
\n\nAll the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
\n\nPolicy last updated: 2016-06-09
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5160},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15608}],offset:12,limit:12,total:117096},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateEndThirdStepPublish'"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:18},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:8},{group:"topic",caption:"Computer and Information Science",value:9,count:11},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:16},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:6},{group:"topic",caption:"Materials Science",value:14,count:5},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:67},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:2},{group:"topic",caption:"Robotics",value:22,count:2},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7796",title:"Human 4.0",subtitle:"From Biology to Cybernetic",isOpenForSubmission:!1,hash:"5ac5c052d3a593d5c4f4df66d005e5af",slug:"human-4-0-from-biology-to-cybernetic",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7796.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9711",title:"Pests, Weeds and Diseases in Agricultural Crop and Animal Husbandry Production",subtitle:null,isOpenForSubmission:!1,hash:"12cf675f1e433135dd5bf5df7cec124f",slug:"pests-weeds-and-diseases-in-agricultural-crop-and-animal-husbandry-production",bookSignature:"Dimitrios Kontogiannatos, Anna Kourti and Kassio Ferreira Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/9711.jpg",editors:[{id:"196691",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kontogiannatos",slug:"dimitrios-kontogiannatos",fullName:"Dimitrios Kontogiannatos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10178",title:"Environmental Emissions",subtitle:null,isOpenForSubmission:!1,hash:"febf21ec717bfe20ae25a9dab9b5d438",slug:"environmental-emissions",bookSignature:"Richard Viskup",coverURL:"https://cdn.intechopen.com/books/images_new/10178.jpg",editors:[{id:"103742",title:"Dr.",name:"Richard",middleName:null,surname:"Viskup",slug:"richard-viskup",fullName:"Richard Viskup"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9534",title:"Banking and Finance",subtitle:null,isOpenForSubmission:!1,hash:"af14229738af402c3b595d7e124dce82",slug:"banking-and-finance",bookSignature:"Razali Haron, Maizaitulaidawati Md Husin and Michael Murg",coverURL:"https://cdn.intechopen.com/books/images_new/9534.jpg",editors:[{id:"206517",title:"Prof.",name:"Razali",middleName:null,surname:"Haron",slug:"razali-haron",fullName:"Razali Haron"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5124},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7796",title:"Human 4.0",subtitle:"From Biology to Cybernetic",isOpenForSubmission:!1,hash:"5ac5c052d3a593d5c4f4df66d005e5af",slug:"human-4-0-from-biology-to-cybernetic",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7796.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9711",title:"Pests, Weeds and Diseases in Agricultural Crop and Animal Husbandry Production",subtitle:null,isOpenForSubmission:!1,hash:"12cf675f1e433135dd5bf5df7cec124f",slug:"pests-weeds-and-diseases-in-agricultural-crop-and-animal-husbandry-production",bookSignature:"Dimitrios Kontogiannatos, Anna Kourti and Kassio Ferreira Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/9711.jpg",editors:[{id:"196691",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kontogiannatos",slug:"dimitrios-kontogiannatos",fullName:"Dimitrios Kontogiannatos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10178",title:"Environmental Emissions",subtitle:null,isOpenForSubmission:!1,hash:"febf21ec717bfe20ae25a9dab9b5d438",slug:"environmental-emissions",bookSignature:"Richard Viskup",coverURL:"https://cdn.intechopen.com/books/images_new/10178.jpg",editors:[{id:"103742",title:"Dr.",name:"Richard",middleName:null,surname:"Viskup",slug:"richard-viskup",fullName:"Richard Viskup"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1253",title:"Industrial Robot",slug:"android-science-industrial-robot",parent:{title:"Android Science",slug:"android-science"},numberOfBooks:2,numberOfAuthorsAndEditors:2,numberOfWosCitations:58,numberOfCrossrefCitations:43,numberOfDimensionsCitations:83,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"android-science-industrial-robot",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"3604",title:"Recent Advances in Multi Robot Systems",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"recent_advances_in_multi_robot_systems",bookSignature:"Aleksandar Lazinica",coverURL:"https://cdn.intechopen.com/books/images_new/3604.jpg",editedByType:"Edited by",editors:[{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3598",title:"Humanitarian Demining",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"humanitarian_demining",bookSignature:"Maki K. Habib",coverURL:"https://cdn.intechopen.com/books/images_new/3598.jpg",editedByType:"Edited by",editors:[{id:"80821",title:"Dr.",name:"Maki K.",middleName:null,surname:"Habib",slug:"maki-k.-habib",fullName:"Maki K. Habib"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,mostCitedChapters:[{id:"875",doi:"10.5772/5477",title:"Flocking Controls for Swarms of Mobile Robots Inspired by Fish Schools",slug:"flocking_controls_for_swarms_of_mobile_robots_inspired_by_fish_schools",totalDownloads:2849,totalCrossrefCites:10,totalDimensionsCites:15,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Geunho Lee and Nak Young Chong",authors:null},{id:"805",doi:"10.5772/5407",title:"Humanitarian Demining: the Problem, Difficulties, Priorities, Demining Technology and the Challenge for Robotics",slug:"humanitarian_demining__the_problem__difficulties__priorities__demining_technology_and_the_challenge_",totalDownloads:3686,totalCrossrefCites:1,totalDimensionsCites:14,book:{slug:"humanitarian_demining",title:"Humanitarian Demining",fullTitle:"Humanitarian Demining"},signatures:"Maki K. Habib",authors:null},{id:"817",doi:"10.5772/5419",title:"Land Robotic Vehicles for Demining",slug:"land_robotic_vehicles_for_demining",totalDownloads:3022,totalCrossrefCites:9,totalDimensionsCites:10,book:{slug:"humanitarian_demining",title:"Humanitarian Demining",fullTitle:"Humanitarian Demining"},signatures:"Stefan Havlik",authors:null}],mostDownloadedChaptersLast30Days:[{id:"887",title:"Mobile Robot Team Forming for Crystallization of Proteins",slug:"mobile_robot_team_forming_for_crystallization_of_proteins",totalDownloads:1623,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Yuan F. Zheng and Weidong Chen",authors:null},{id:"884",title:"A Novel Modeling Method for Cooperative Multirobot Systems Using Fuzzy Timed Agent Based Petri Nets",slug:"a_novel_modeling_method_for_cooperative_multirobot_systems_using_fuzzy_timed_agent_based_petri_nets",totalDownloads:1935,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Hua Xu",authors:null},{id:"877",title:"Dispersion and Dispatch Movement Design for a Multi-Robot Searching Team Using Communication Density",slug:"dispersion_and_dispatch_movement_design_for_a_multi-robot_searching_team_using_communication_density",totalDownloads:1946,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Feng-Li Lian, You-Ling Jian and Wei-Hao Hsu",authors:null},{id:"820",title:"Power Tillers for Demining in Sri Lanka: Participatory Design of Low-cost Technology",slug:"power_tillers_for_demining_in_sri_lanka__participatory_design_of_low-cost_technology",totalDownloads:3503,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"humanitarian_demining",title:"Humanitarian Demining",fullTitle:"Humanitarian Demining"},signatures:"Cepolina Emanuela Elisa",authors:null},{id:"875",title:"Flocking Controls for Swarms of Mobile Robots Inspired by Fish Schools",slug:"flocking_controls_for_swarms_of_mobile_robots_inspired_by_fish_schools",totalDownloads:2849,totalCrossrefCites:10,totalDimensionsCites:15,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Geunho Lee and Nak Young Chong",authors:null},{id:"885",title:"Cooperative Control of Multiple Biomimetic Robotic Fish",slug:"cooperative_control_of_multiple_biomimetic_robotic_fish",totalDownloads:2762,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Junzhi Yu, Min Tan and Long Wang",authors:null},{id:"881",title:"A User Multi-Robot System Interaction Paradigm for a Multi-Robot Mission Editor",slug:"a_user_multi-robot_system_interaction_paradigm_for_a_multi-robot_mission_editor",totalDownloads:1586,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Saidi Francois and Pradel Gilbert",authors:null},{id:"872",title:"A Networking Framework for Multi-Robot Coordination",slug:"a_networking_framework_for_multi-robot_coordination",totalDownloads:1921,totalCrossrefCites:3,totalDimensionsCites:3,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Antonio Chella, Giuseppe Lo Re, Irene Macaluso, Marco Ortolani and Daniele Peri",authors:null},{id:"819",title:"A Human-Animal-Robot Cooperative System for Anti-Personal Mine Detection",slug:"a_human-animal-robot_cooperative_system_for_anti-personal_mine_detection",totalDownloads:2521,totalCrossrefCites:4,totalDimensionsCites:6,book:{slug:"humanitarian_demining",title:"Humanitarian Demining",fullTitle:"Humanitarian Demining"},signatures:"Thrishantha Nanayakkara, Tharindu Dissanayake, Prasanna Mahipala and K. A. Gayan Sanjaya",authors:null},{id:"883",title:"Formation Control for Non-Holonomic Mobile Robots: A Hybrid Approach",slug:"formation_control_for_non-holonomic_mobile_robots__a_hybrid_approach",totalDownloads:2270,totalCrossrefCites:0,totalDimensionsCites:3,book:{slug:"recent_advances_in_multi_robot_systems",title:"Recent Advances in Multi Robot Systems",fullTitle:"Recent Advances in Multi Robot Systems"},signatures:"Juan Marcos Toibero, Flavio Roberti, Ricardo Carelli and Paolo Fiorini",authors:null}],onlineFirstChaptersFilter:{topicSlug:"android-science-industrial-robot",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/109333/peter-pong",hash:"",query:{},params:{id:"109333",slug:"peter-pong"},fullPath:"/profiles/109333/peter-pong",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()