Technical methods of application VCR technology in piston engines and their technical and operational features.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{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"}]},book:{item:{type:"book",id:"4503",leadTitle:null,fullTitle:"Selected Topics in Applications of Quantum Mechanics",title:"Selected Topics in Applications of Quantum Mechanics",subtitle:null,reviewType:"peer-reviewed",abstract:"This book has two sections. The section Selected Topics in Applications of Quantum Mechanics provides seven chapters about different applications of quantum mechanics in science and technology.\nThe section Selected Topics in Foundations of Quantum Mechanics provides seven chapters about the foundations of quantum mechanics.\nThis book is written by a community of expert scientists from different research institutes and universities from all over the world. \nWithout a doubt, quantum mechanics is the greatest discovery of the 20th century. Therefore, its history and foundations are of great interest to scientists and students. This book covers some of the applications of quantum mechanics in nuclear physics, medical science, information technology, atomic physics and material science, as well as selected topics of quantum mechanics through different bases and ideas about quantum mechanics. The basic idea of the publication of this book is to make scientists and researchers, as well as graduate students, familiar with the foundations of quantum mechanics.",isbn:null,printIsbn:"978-953-51-2126-8",pdfIsbn:"978-953-51-5056-5",doi:"10.5772/58514",price:139,priceEur:155,priceUsd:179,slug:"selected-topics-in-applications-of-quantum-mechanics",numberOfPages:468,isOpenForSubmission:!1,isInWos:1,hash:"49ea5b364e379eac3ca7747bc170c217",bookSignature:"Mohammad Reza Pahlavani",publishedDate:"May 13th 2015",coverURL:"https://cdn.intechopen.com/books/images_new/4503.jpg",numberOfDownloads:20154,numberOfWosCitations:14,numberOfCrossrefCitations:18,numberOfDimensionsCitations:24,hasAltmetrics:1,numberOfTotalCitations:56,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 24th 2014",dateEndSecondStepPublish:"May 15th 2014",dateEndThirdStepPublish:"August 19th 2014",dateEndFourthStepPublish:"November 17th 2014",dateEndFifthStepPublish:"December 17th 2014",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"101263",title:"Prof.",name:"Mohammad Reza",middleName:null,surname:"Pahlavani",slug:"mohammad-reza-pahlavani",fullName:"Mohammad Reza Pahlavani",profilePictureURL:"https://mts.intechopen.com/storage/users/101263/images/system/101263.jpg",biography:"Dr. Mohammad Reza Pahlavani was born on March 1958 in Daregaz, a city in the North of Khorasan Razavi Providence. He received his BSc from the Ferdowsi University of Mashad, MSc from the Tehran University and PhD from the Indian Institute of Technology Bombay-Mumbai India in experimental nuclear physics. He occupied the faculty member position in August 1991 and continued his duties as a professor in the Department of Nuclear Physics, Faculty of Basic Sciences - University of Mazandaran, Iran since. He has published more than 100 papers in ISI journals, mostly in Physical Review C, European physical journal A, International journal of modern physics A, Journal of physics G. He presented about 100 papers in national and international conferences and has written 5 books (one in Persian language) as author and 4 as editor in English language.",institutionString:"University of Mazandaran",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"University of Mazandaran",institutionURL:null,country:{name:"Iran"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1237",title:"Theoretical Physics",slug:"theoretical-physics"}],chapters:[{id:"47703",title:"Classical or Quantum? What is Reality?",doi:"10.5772/59115",slug:"classical-or-quantum-what-is-reality-",totalDownloads:1432,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"J. J. Sławianowski and V. Kovalchuk",downloadPdfUrl:"/chapter/pdf-download/47703",previewPdfUrl:"/chapter/pdf-preview/47703",authors:[{id:"103754",title:"Prof.",name:"Jan",surname:"Slawianowski",slug:"jan-slawianowski",fullName:"Jan Slawianowski"},{id:"172992",title:"Dr.",name:"Vasyl",surname:"Kovalchuk",slug:"vasyl-kovalchuk",fullName:"Vasyl Kovalchuk"}],corrections:null},{id:"47683",title:"Photons and Signals in the Age of Information",doi:"10.5772/59067",slug:"photons-and-signals-in-the-age-of-information",totalDownloads:1243,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Cynthia Kolb Whitney",downloadPdfUrl:"/chapter/pdf-download/47683",previewPdfUrl:"/chapter/pdf-preview/47683",authors:[{id:"103463",title:"Dr.",name:"Cynthia",surname:"Whitney",slug:"cynthia-whitney",fullName:"Cynthia Whitney"}],corrections:null},{id:"47652",title:"Path Integral Methods in Generalized Uncertainty Principle",doi:"10.5772/59106",slug:"path-integral-methods-in-generalized-uncertainty-principle",totalDownloads:1366,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Hadjira Benzair, Mahmoud Merad and Taher Boudjedaa",downloadPdfUrl:"/chapter/pdf-download/47652",previewPdfUrl:"/chapter/pdf-preview/47652",authors:[{id:"162659",title:"Prof.",name:"Mahmoud",surname:"Merad",slug:"mahmoud-merad",fullName:"Mahmoud Merad"},{id:"173057",title:"Prof.",name:"Boudjedaa",surname:"Tahar",slug:"boudjedaa-tahar",fullName:"Boudjedaa Tahar"},{id:"173058",title:"Dr.",name:"Benzair",surname:"Hadjira",slug:"benzair-hadjira",fullName:"Benzair Hadjira"}],corrections:null},{id:"47773",title:"Unification of Quantum Mechanics with the Relativity Theory, Based on Discrete Conservations of Energy and Gravity",doi:"10.5772/59169",slug:"unification-of-quantum-mechanics-with-the-relativity-theory-based-on-discrete-conservations-of-energ",totalDownloads:1439,totalCrossrefCites:3,totalDimensionsCites:3,signatures:"Aghaddin Mamedov",downloadPdfUrl:"/chapter/pdf-download/47773",previewPdfUrl:"/chapter/pdf-preview/47773",authors:[{id:"92808",title:"Prof.",name:"Aghaddin",surname:"Mamedov",slug:"aghaddin-mamedov",fullName:"Aghaddin Mamedov"}],corrections:null},{id:"47634",title:"The Measurement Problem in Quantum Mechanics Revisited",doi:"10.5772/59209",slug:"the-measurement-problem-in-quantum-mechanics-revisited",totalDownloads:1507,totalCrossrefCites:4,totalDimensionsCites:6,signatures:"M. E. Burgos",downloadPdfUrl:"/chapter/pdf-download/47634",previewPdfUrl:"/chapter/pdf-preview/47634",authors:[{id:"96880",title:"Prof.",name:"Maria Esther",surname:"Burgos",slug:"maria-esther-burgos",fullName:"Maria Esther Burgos"}],corrections:null},{id:"47728",title:"The Computational Unified Field Theory (CUFT) – Revising Quantum & Relativistic Models",doi:"10.5772/59175",slug:"the-computational-unified-field-theory-cuft-revising-quantum-relativistic-models",totalDownloads:1180,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Jehonathan Bentwich",downloadPdfUrl:"/chapter/pdf-download/47728",previewPdfUrl:"/chapter/pdf-preview/47728",authors:[{id:"99692",title:"Dr.",name:"Jonathan",surname:"Bentwich",slug:"jonathan-bentwich",fullName:"Jonathan Bentwich"}],corrections:null},{id:"47613",title:"A Lie-QED-Algebra and their Fermionic Fock Space in the Superconducting Phenomena",doi:"10.5772/59078",slug:"a-lie-qed-algebra-and-their-fermionic-fock-space-in-the-superconducting-phenomena",totalDownloads:1133,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Francisco Bulnes",downloadPdfUrl:"/chapter/pdf-download/47613",previewPdfUrl:"/chapter/pdf-preview/47613",authors:[{id:"92918",title:"Dr.",name:"Francisco",surname:"Bulnes",slug:"francisco-bulnes",fullName:"Francisco Bulnes"}],corrections:null},{id:"48411",title:"The Nuclear Mean Field Theory and Its Application to Nuclear Physics",doi:"10.5772/60517",slug:"the-nuclear-mean-field-theory-and-its-application-to-nuclear-physics",totalDownloads:1542,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"M.R. Pahlavani",downloadPdfUrl:"/chapter/pdf-download/48411",previewPdfUrl:"/chapter/pdf-preview/48411",authors:[{id:"101263",title:"Prof.",name:"Mohammad Reza",surname:"Pahlavani",slug:"mohammad-reza-pahlavani",fullName:"Mohammad Reza Pahlavani"}],corrections:null},{id:"47705",title:"Non-Extensive Entropies on Atoms, Molecules and Chemical Processes",doi:"10.5772/59139",slug:"non-extensive-entropies-on-atoms-molecules-and-chemical-processes",totalDownloads:1268,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"N. Flores-Gallegos, I. Guillén-Escamilla and J.C. Mixteco-Sánchez",downloadPdfUrl:"/chapter/pdf-download/47705",previewPdfUrl:"/chapter/pdf-preview/47705",authors:[{id:"171253",title:"Dr.",name:"Nelson",surname:"Flores-Gallegos",slug:"nelson-flores-gallegos",fullName:"Nelson Flores-Gallegos"}],corrections:null},{id:"47559",title:"Computation of Materials Properties at the Atomic Scale",doi:"10.5772/59108",slug:"computation-of-materials-properties-at-the-atomic-scale",totalDownloads:2298,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"Karlheinz Schwarz",downloadPdfUrl:"/chapter/pdf-download/47559",previewPdfUrl:"/chapter/pdf-preview/47559",authors:[{id:"171618",title:"Emeritus Prof.",name:"Karlheinz",surname:"Schwarz",slug:"karlheinz-schwarz",fullName:"Karlheinz Schwarz"}],corrections:null},{id:"47651",title:"Implications of Quantum Informational Entropy in Some Fundamental Physical and Biophysical Models",doi:"10.5772/59203",slug:"implications-of-quantum-informational-entropy-in-some-fundamental-physical-and-biophysical-models",totalDownloads:1349,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Maricel Agop, Alina Gavriluț, Călin Buzea, Lăcrămioara Ochiuz, Dan\nTesloianu, Gabriel Crumpei and Cristina Popa",downloadPdfUrl:"/chapter/pdf-download/47651",previewPdfUrl:"/chapter/pdf-preview/47651",authors:[{id:"24020",title:"Dr.",name:"Maricel",surname:"Agop",slug:"maricel-agop",fullName:"Maricel Agop"},{id:"99400",title:"Dr.",name:"Calin Gheorghe",surname:"Buzea",slug:"calin-gheorghe-buzea",fullName:"Calin Gheorghe Buzea"},{id:"171634",title:"Dr.",name:"Alina",surname:"Gavrilut",slug:"alina-gavrilut",fullName:"Alina Gavrilut"},{id:"171636",title:"Dr.",name:"Lacramioara",surname:"Ochiuz",slug:"lacramioara-ochiuz",fullName:"Lacramioara Ochiuz"},{id:"171638",title:"Dr.",name:"Cristina",surname:"Popa",slug:"cristina-popa",fullName:"Cristina Popa"},{id:"173061",title:"Dr.",name:"Gabriel",surname:"Crumpei",slug:"gabriel-crumpei",fullName:"Gabriel Crumpei"},{id:"173062",title:"Dr.",name:"Dan",surname:"Tesloianu",slug:"dan-tesloianu",fullName:"Dan Tesloianu"}],corrections:null},{id:"47567",title:"Physical Vacuum is a Special Superfluid Medium",doi:"10.5772/59040",slug:"physical-vacuum-is-a-special-superfluid-medium",totalDownloads:1847,totalCrossrefCites:11,totalDimensionsCites:13,signatures:"V.I. Sbitnev",downloadPdfUrl:"/chapter/pdf-download/47567",previewPdfUrl:"/chapter/pdf-preview/47567",authors:[{id:"93881",title:"Dr.",name:"Valeriy",surname:"Sbitnev",slug:"valeriy-sbitnev",fullName:"Valeriy Sbitnev"}],corrections:null},{id:"47611",title:"Husimi Distribution and the Fisher Information",doi:"10.5772/59126",slug:"husimi-distribution-and-the-fisher-information",totalDownloads:1153,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Sergio Curilef and Flavia Pennini",downloadPdfUrl:"/chapter/pdf-download/47611",previewPdfUrl:"/chapter/pdf-preview/47611",authors:[{id:"125424",title:"Prof.",name:"Sergio",surname:"Curilef",slug:"sergio-curilef",fullName:"Sergio Curilef"}],corrections:null},{id:"47818",title:"Implications of the “Subquantum Level” in Carcinogenesis and Tumor Progression via Scale Relativity Theory",doi:"10.5772/59233",slug:"implications-of-the-subquantum-level-in-carcinogenesis-and-tumor-progression-via-scale-relativity-th",totalDownloads:1413,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Daniel Timofte, Lucian Eva, Decebal Vasincu, Călin Gh. Buzea,\nMaricel Agop and Radu Florin Popa",downloadPdfUrl:"/chapter/pdf-download/47818",previewPdfUrl:"/chapter/pdf-preview/47818",authors:[{id:"24020",title:"Dr.",name:"Maricel",surname:"Agop",slug:"maricel-agop",fullName:"Maricel Agop"},{id:"99400",title:"Dr.",name:"Calin Gheorghe",surname:"Buzea",slug:"calin-gheorghe-buzea",fullName:"Calin Gheorghe Buzea"},{id:"173047",title:"Dr.",name:"Daniel",surname:"Timofte",slug:"daniel-timofte",fullName:"Daniel Timofte"},{id:"173048",title:"Dr.",name:"Lucian",surname:"Eva",slug:"lucian-eva",fullName:"Lucian Eva"},{id:"173049",title:"Dr.",name:"Decebal",surname:"Vasincu",slug:"decebal-vasincu",fullName:"Decebal Vasincu"},{id:"173050",title:"Dr.",name:"Radu Florin",surname:"Popa",slug:"radu-florin-popa",fullName:"Radu Florin Popa"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"1613",title:"Theoretical Concepts of Quantum Mechanics",subtitle:null,isOpenForSubmission:!1,hash:"f9c6e9ac171d39eecb718608fb626430",slug:"theoretical-concepts-of-quantum-mechanics",bookSignature:"Mohammad Reza Pahlavani",coverURL:"https://cdn.intechopen.com/books/images_new/1613.jpg",editedByType:"Edited by",editors:[{id:"101263",title:"Prof.",name:"Mohammad Reza",surname:"Pahlavani",slug:"mohammad-reza-pahlavani",fullName:"Mohammad Reza Pahlavani"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2138",title:"Measurements in Quantum Mechanics",subtitle:null,isOpenForSubmission:!1,hash:"3487ee0a57a3bb9087dcf65c25e1b73d",slug:"measurements-in-quantum-mechanics",bookSignature:"Mohammad Reza Pahlavani",coverURL:"https://cdn.intechopen.com/books/images_new/2138.jpg",editedByType:"Edited by",editors:[{id:"101263",title:"Prof.",name:"Mohammad Reza",surname:"Pahlavani",slug:"mohammad-reza-pahlavani",fullName:"Mohammad Reza Pahlavani"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2139",title:"Some Applications of Quantum Mechanics",subtitle:null,isOpenForSubmission:!1,hash:"78dac0afd6b5ae98402487ae1f1e836f",slug:"some-applications-of-quantum-mechanics",bookSignature:"Mohammad Reza Pahlavani",coverURL:"https://cdn.intechopen.com/books/images_new/2139.jpg",editedByType:"Edited by",editors:[{id:"101263",title:"Prof.",name:"Mohammad Reza",surname:"Pahlavani",slug:"mohammad-reza-pahlavani",fullName:"Mohammad Reza Pahlavani"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3513",title:"Advances in Quantum Mechanics",subtitle:null,isOpenForSubmission:!1,hash:"bbea1c081216f267a4480707f4ead9cf",slug:"advances-in-quantum-mechanics",bookSignature:"Paul Bracken",coverURL:"https://cdn.intechopen.com/books/images_new/3513.jpg",editedByType:"Edited by",editors:[{id:"92883",title:"Prof.",name:"Paul",surname:"Bracken",slug:"paul-bracken",fullName:"Paul Bracken"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1635",title:"Advances in Quantum Field Theory",subtitle:null,isOpenForSubmission:!1,hash:"f85baa6050940f123e42742ad20e437c",slug:"advances-in-quantum-field-theory",bookSignature:"Sergey Ketov",coverURL:"https://cdn.intechopen.com/books/images_new/1635.jpg",editedByType:"Edited by",editors:[{id:"106742",title:"Prof.",name:"Sergey",surname:"Ketov",slug:"sergey-ketov",fullName:"Sergey Ketov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1615",title:"Advances in Quantum Theory",subtitle:null,isOpenForSubmission:!1,hash:"292f0a763e50627eed224ef40ec75962",slug:"advances-in-quantum-theory",bookSignature:"Ion I. Cotaescu",coverURL:"https://cdn.intechopen.com/books/images_new/1615.jpg",editedByType:"Edited by",editors:[{id:"108083",title:"Prof.",name:"Ion",surname:"Cotaescu",slug:"ion-cotaescu",fullName:"Ion Cotaescu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1861",title:"Wavelet Transforms and Their Recent Applications in Biology and Geoscience",subtitle:null,isOpenForSubmission:!1,hash:"17f3d0e20293bdad1d8f4c760e6826b3",slug:"wavelet-transforms-and-their-recent-applications-in-biology-and-geoscience",bookSignature:"Dumitru Baleanu",coverURL:"https://cdn.intechopen.com/books/images_new/1861.jpg",editedByType:"Edited by",editors:[{id:"105623",title:"Dr.",name:"Dumitru",surname:"Baleanu",slug:"dumitru-baleanu",fullName:"Dumitru Baleanu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1660",title:"Quantum Gravity",subtitle:null,isOpenForSubmission:!1,hash:"f5e880374e06a33f8c90db6877074d51",slug:"quantum-gravity",bookSignature:"Rodrigo Sobreiro",coverURL:"https://cdn.intechopen.com/books/images_new/1660.jpg",editedByType:"Edited by",editors:[{id:"101446",title:"Dr.",name:"Rodrigo",surname:"Sobreiro",slug:"rodrigo-sobreiro",fullName:"Rodrigo Sobreiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7788",title:"Progress in Relativity",subtitle:null,isOpenForSubmission:!1,hash:"258de121f66ce548dbf7a88bc569b58e",slug:"progress-in-relativity",bookSignature:"Calin Gheorghe Buzea, Maricel Agop and Leo Butler",coverURL:"https://cdn.intechopen.com/books/images_new/7788.jpg",editedByType:"Edited by",editors:[{id:"99400",title:"Dr.",name:"Calin Gheorghe",surname:"Buzea",slug:"calin-gheorghe-buzea",fullName:"Calin Gheorghe Buzea"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"71744",slug:"corrigendum-to-technical-advances-in-chloroplast-biotechnology",title:"Corrigendum to: Technical Advances in Chloroplast Biotechnology",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/71744.pdf",downloadPdfUrl:"/chapter/pdf-download/71744",previewPdfUrl:"/chapter/pdf-preview/71744",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/71744",risUrl:"/chapter/ris/71744",chapter:{id:"65358",slug:"technical-advances-in-chloroplast-biotechnology",signatures:"Muhammad Sarwar Khan, Ghulam Mustafa and Faiz Ahmad Joyia",dateSubmitted:"June 12th 2018",dateReviewed:"August 31st 2018",datePrePublished:"January 25th 2019",datePublished:"October 23rd 2019",book:{id:"6976",title:"Transgenic Crops",subtitle:"Emerging Trends and Future Perspectives",fullTitle:"Transgenic Crops - Emerging Trends and Future Perspectives",slug:"transgenic-crops-emerging-trends-and-future-perspectives",publishedDate:"October 23rd 2019",bookSignature:"Muhammad Sarwar Khan and Kauser Abdulla Malik",coverURL:"https://cdn.intechopen.com/books/images_new/6976.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"212511",title:"Prof.",name:"Muhammad Sarwar",middleName:null,surname:"Khan",slug:"muhammad-sarwar-khan",fullName:"Muhammad Sarwar Khan"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"211046",title:"Dr.",name:"Ghulam",middleName:null,surname:"Mustafa",fullName:"Ghulam Mustafa",slug:"ghulam-mustafa",email:"drmustafa8@gmail.com",position:null,institution:{name:"University of Agriculture Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"212508",title:"Dr.",name:"Faiz",middleName:null,surname:"Ahmad",fullName:"Faiz Ahmad",slug:"faiz-ahmad",email:"faizahmad1980@gmail.com",position:null,institution:null},{id:"212511",title:"Prof.",name:"Muhammad Sarwar",middleName:null,surname:"Khan",fullName:"Muhammad Sarwar Khan",slug:"muhammad-sarwar-khan",email:"sarwarkhan_40@hotmail.com",position:null,institution:{name:"University of Agriculture Faisalabad",institutionURL:null,country:{name:"Pakistan"}}}]}},chapter:{id:"65358",slug:"technical-advances-in-chloroplast-biotechnology",signatures:"Muhammad Sarwar Khan, Ghulam Mustafa and Faiz Ahmad Joyia",dateSubmitted:"June 12th 2018",dateReviewed:"August 31st 2018",datePrePublished:"January 25th 2019",datePublished:"October 23rd 2019",book:{id:"6976",title:"Transgenic Crops",subtitle:"Emerging Trends and Future Perspectives",fullTitle:"Transgenic Crops - Emerging Trends and Future Perspectives",slug:"transgenic-crops-emerging-trends-and-future-perspectives",publishedDate:"October 23rd 2019",bookSignature:"Muhammad Sarwar Khan and Kauser Abdulla Malik",coverURL:"https://cdn.intechopen.com/books/images_new/6976.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"212511",title:"Prof.",name:"Muhammad Sarwar",middleName:null,surname:"Khan",slug:"muhammad-sarwar-khan",fullName:"Muhammad Sarwar Khan"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"211046",title:"Dr.",name:"Ghulam",middleName:null,surname:"Mustafa",fullName:"Ghulam Mustafa",slug:"ghulam-mustafa",email:"drmustafa8@gmail.com",position:null,institution:{name:"University of Agriculture Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"212508",title:"Dr.",name:"Faiz",middleName:null,surname:"Ahmad",fullName:"Faiz Ahmad",slug:"faiz-ahmad",email:"faizahmad1980@gmail.com",position:null,institution:null},{id:"212511",title:"Prof.",name:"Muhammad Sarwar",middleName:null,surname:"Khan",fullName:"Muhammad Sarwar Khan",slug:"muhammad-sarwar-khan",email:"sarwarkhan_40@hotmail.com",position:null,institution:{name:"University of Agriculture Faisalabad",institutionURL:null,country:{name:"Pakistan"}}}]},book:{id:"6976",title:"Transgenic Crops",subtitle:"Emerging Trends and Future Perspectives",fullTitle:"Transgenic Crops - Emerging Trends and Future Perspectives",slug:"transgenic-crops-emerging-trends-and-future-perspectives",publishedDate:"October 23rd 2019",bookSignature:"Muhammad Sarwar Khan and Kauser Abdulla Malik",coverURL:"https://cdn.intechopen.com/books/images_new/6976.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"212511",title:"Prof.",name:"Muhammad Sarwar",middleName:null,surname:"Khan",slug:"muhammad-sarwar-khan",fullName:"Muhammad Sarwar Khan"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10203",leadTitle:null,title:"Dyes and Pigments",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tThe use of dyes and pigments is narrowly associated with everyday life. Since ancient times, people have been using various types of dyes and pigments for both aesthetic and practical applications. Typically, the coloration of various materials e.g. textiles, clay, plastics, etc. has been their main purpose. Yet, the scope of contemporary dyes and pigments has become significantly broader and there is constant interest in new products fulfilling numerous requirements parallel to their ability to act as colorants. This trend has led to the development of functional dyes.
\r\n\r\n\tIn recent years, novel dyes and pigments with hi-tech applications have been developed and there is a continuous demand for new products with better properties and/or broader application scope. Of particular interest is the development of dyes and pigments with environment-responsive aptitudes i.e. products that can undergo some structural modification as a result of external stimuli e.g. light, heat, pressure, pH-changes, etc. These stimuli-responsive functional dyes have in turn found application in sensor technologies, optical data storage, molecular switches, etc. Acknowledging these facts, this book aims to cover current state-of-the-art research and development in the remarkably important area of environment-responsive (multi)functional dyes and pigments.
",isbn:"978-1-83968-615-3",printIsbn:"978-1-83968-614-6",pdfIsbn:"978-1-83968-616-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"624f533946a159bc8a03f109c2e1dc91",bookSignature:"Dr. Raffaello Papadakis",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10203.jpg",keywords:"Fluorescent Dyes, PH-Sensitive Dyes, Solvatochromism, Solvent Polarity Indicators, Chromic Betaines, Viscosity, Charge-Transfer Complexes, Spectroscopy, Piezochromism, Optoelectronics, Photochromism, Molecular Switches",numberOfDownloads:62,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 28th 2020",dateEndSecondStepPublish:"September 25th 2020",dateEndThirdStepPublish:"November 24th 2020",dateEndFourthStepPublish:"February 12th 2021",dateEndFifthStepPublish:"April 13th 2021",remainingDaysToSecondStep:"5 months",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Chemical Engineer with working experience at the Institute of Molecular Sciences, CNRS/Aix-Marseille University in the research group of Dr. Thierry Tron, and at Uppsala University in the research group of Dr. Henrik Ottosson. Currently a Senior Research Scientist at Tdb Labs, Uppsala, Sweden.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"251885",title:"Dr.",name:"Raffaello",middleName:null,surname:"Papadakis",slug:"raffaello-papadakis",fullName:"Raffaello Papadakis",profilePictureURL:"https://mts.intechopen.com/storage/users/251885/images/system/251885.jpg",biography:"Raffaello Papadakis is a Chemical Engineer (MEng 2005) majoring in organic chemical technology and polymer science and technology. He started his PhD in the field of physical organic chemistry in 2006 under the supervision of Prof. (Emer.) Dr. Athanase Tsolomitis (National Technical University of Athens, Greece) and graduated in 2010. During his PhD he concentrated on the synthesis of solvatochromic probes and molecular switches. He later on spent two years in Marseille, France (September 2010–January 2013) working as a postodoctoral researcher at the Institute of Molecular Sciences, CNRS/Aix-Marseille University, in the field of water oxidation catalysts in the research group of Dr. Thierry Tron before moving to to Uppsala, Sweden in 2014. There he joined the group of Dr. Henrik Ottosson (Uppsala University) and he worked as a postdoc researcher and later as a researcher (Forskare) focusing on excited state (anti)aromaticity and graphene photochemistry-related research. His current research interests revolve around physical organic and materials chemistry with an emphasis on the chemistry and photochemistry of graphene and novel covalent organic frameworks as well as polymer chemistry. He is the author and coauthor of 24 scientific research papers, two book chapters and he has more than 35 contributions in international conference proceedings. Furthermore, he is an active referee of scientific peer-reviewed papers of world-class chemistry journals and he has acted as a scientific expert evaluating international research-grant proposals. Currently he works as a Senior Research Scientist at TdB Labs AB (Sweden) and specializes in polysaccharide modifications and derivatization placing particular interest in fluorescent dye polysaccharide-functionalizations.",institutionString:"TdB Labs",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:[{id:"74730",title:"Treatment of Textile Dyeing Waste Water Using TiO2/Zn Electrode by Spray Pyrolysis in Electrocoagulation Process",slug:"treatment-of-textile-dyeing-waste-water-using-tio2-zn-electrode-by-spray-pyrolysis-in-electrocoagula",totalDownloads:63,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"247865",firstName:"Jasna",lastName:"Bozic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/247865/images/7225_n.jpg",email:"jasna.b@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"16940",title:"Eukaryotic Replication Barriers: How, Why and Where Forks Stall",doi:"10.5772/20383",slug:"eukaryotic-replication-barriers-how-why-and-where-forks-stall",body:'\n\t\tMaintaining genetic fidelity is paramount for all living organisms. The process of replicating DNA is especially dangerous for cells. Not only must the genetic sequence be replicated precisely by the replicative polymerases, but stalled replication forks and single-stranded DNA present at the forks increase risks of chromosome breakage leading to rearrangements. Also, once the cell commits itself to the replication process it has to be fully completed before chromosomes can be disentangled and condensed prior to their proper segregation in the subsequent mitosis. Many processes have evolved that ensure the precision and stability of the replication process; helicases remove bound proteins in front of the fork, topoisomerases ensure that topological entanglements generated during replication are resolved; checkpoint activation in response to stalled replication forks controls an array of molecular responses, repair polymerases and proteins to be recruited to stalled replication forks to allow replication restart; moreover, origin firing is controlled such that firing of origins is delayed in response to the replication checkpoint and dormant origins can be activated if replication is not completed. It is at first hand therefore surprising that at specific loci in the genome, molecular mechanisms exist where deliberate pausing or termination of the replication fork occur. This wonder is further confounded by the fact that several studies have shown that these replication barriers cause genetic instability (see MacFarlane, Al-Zeer and Dalgaard, Chapter 16). What the evolutionary benefits of these replication barriers might be remains a major question. More and more evidence is accumulating that indicates many replication barriers have opposing effects on genome stability; on one hand they promote genetic stability though a controlled stalling of the replication fork at specific sites or situations, however, in doing so they potentially cause fork collapse and genetic instability. In many cases these barriers “coordinate” transcription and replication, preventing collisions between the two types of enzymatic complexes, suggesting that such collisions are more detrimental to the stability of the genome than the instability induced by stalling at a replication barrier (references are given in the main text). Thus, one might argue that most replication barriers evolved to promote genetic stability while allowing “controlled” genetic instability, although other functions of replication barriers are also evident. Here, we review what different types of natural replication impediments are known, how they prevent replication fork progression, and what potential biological function they have.
\n\t\tEpstein-Barr virus or human herpes virus 4 DNA is replicated once per cell-cycle in latently infected cells. Here the DNA binding EBNA-1 protein plays several important roles for viral replication. First, EBNA-1 binds to inverted repeats at the cis-acting OriP sequence, where it acts to recruit cellular ORC proteins and as a consequence, other replication factors required for replication. Binding to the OriP sequence occurs at a region with dyad symmetry containing four low-affinity binding sites for EBNA-1 (Ambinder, et al. 1990). However, EBNA-1 also interacts with another region within OriP called FR (family of repeats), which contains twenty 30-bp high-affinity sites for the EBNA-1 dimer (Rawlins, et al. 1985). When replication is initiated at OriP it proceeds in a bi-directional manner but the replication fork moving toward FR is stalled by the bound EBNA-1, thus converting the bi-directional replication process into an uni-directional replication one. Reducing the number of FR repeats from 20 to 15, 6, 2 or 0 showed that 6, 15 or 20 copies promoted barrier activity (Dhar & Schildkraut, 1991). The FR region with bound EBNA-1 acts both as a barrier for the cellular MCM replicative helicase during viral replication as well as the SV40 large T-antigen for SV40 plasmids. The latter barrier activity has been observed both in vitro and in vivo (Dhar & Schildkraut, 1991, Ermakova, et al. 1996, Aiyar, et al. 2009). EBNA-1 also prevents strand unwinding by both the SV40 large T-antigen 3’ to 5’ helicase and the E. coli dnaB 5’ to 3’ helicase (Ermakova, et al. 1996). Interestingly, FR/EBNA-1 complexes containing 20 or 40 repeats also act as a barrier to RNA polymerase II transcription, and since a viral transcript (although catalysed by RNA polymerase III; Howe & Shu, 1989; Howe & Shu, 1993) is oriented toward FR, the FR/EBNA-1 barrier could have a role in preventing collisions between transcription and replication forks (Aiyar, et al. 2009). In addition to its role in replication, the FR/EBNA-1 element is also required for maintenance and partitioning of viral DNA. The element tethers the viral episome to a cellular chromosome, thereby allowing appropriate segregation into the daughter cells (Marechal, et al. 1999; Sears, et al. 2003; Sears, et al. 2004). Interestingly, the FR/EBNA-1 element also has a negative effect on plasmid maintenance; puromycin resistance encoding plasmids containing 20 or more copies of the element are not efficiently maintained in cell culture (Aiyar, et al. 2009). Thus, the FR/EBNA-1 replication barrier element might have both negative and positive effects on viral copy number.
\n\t\tMost organisms share the same basic arrangement of the rDNA, consisting of one or more arrays of a genetic unit, where each unit contains a RNA polymerase I transcribed pre-curser rRNA encoding the 25-28S large rRNA, the 16-18S small rRNA as well as the 5.8 S rRNAs. The latter is separated from the origin of replication by a non-transcribed spacer (NTS). This NTS contains one or more replication barriers that pause or stall replication forks, thus preventing them from entering the polymerase I transcribed unit. Such barriers have been described in many different organisms, including fission yeast (Schizosaccharomyces pombe), budding yeast (Saccharomyces cerevisiae), ciliated protozoa (Tetrahymena thermophila), Pea (Pisum sativum), frog (Xenopus laevis), mouse (Mus musculus) and human (see below for references). Generally these barriers are thought to prevent collisions (and therefore genetic instability) between the polymerase I transcription bubbles and the replication forks moving in opposite directions, but data suggests that they have both a positive and a negative effect on genome stability (see below).
\n\t\t\t2D-gel analysis of the rDNA of P. sativum detected several replication barriers in the NTS, located just downstream the RNA polymerase I transcript. The P. sativum replication barrier region maps to a 27 base pair direct repeat region with the consensus sequence TCCGCC(T/A)CTTGT-ATTCGTTGCGTTG(A/C)A that is either present in 9 or 3 copies in two different classes of arrays (Hernandez, et al. 1988; Hernandez, et al. 1993; Lopez-Estrano, et al. 1999). This repeated sequence motif shows some similarity with the sequence that mediates barrier activity in S. cerevisia (Hernandez, et al. 1993), and mobility shifts indicate that an unknown transacting factor(s) can bind to the repeats (Lopez-Estrano, et al. 1999).
\n\t\t\tIn T. thermophila the rDNA barriers are developmentally regulated. In the germ line micronucleus the 10.3 kb rDNA is present in a single copy, while in the differentiated macro nucleus the rDNA has been excised from the genome, arranged into an inverted repeat (the two polymerase I transcripts arranged in opposite directions), telomeres are added and the repeat is amplified 10000 fold (Reviewed in Tower, 2004). This amplification occurs within one cell cycle. Interestingly, here the 5’ NTS contains three replication barriers that pause the replication fork in a polar manner (MacAlpine, et al. 1997). These barriers are located between the site of replication initiation (that occurs at two sites flanking the centre of the inverted repeat) and the polymerase I transcript. Thus, here the barriers are upstream of the RNA polymerase I transcript. The consensus sequence of the three cis-acting sequences is 5’ A(A/T)TTTCANNNNNNNNNNNNNNNNNNA(A/G)TTTCATTCANNNNNNNNNTTTTTTTT 3’. These replication pause sites are active both during vegetative growth and when amplification occurs. In addition to the three pause sites, an additional replication barrier is present which only acts during amplification and not during vegetative growth. This barrier is present in the middle of the palindrome and acts to stall the fork until a converging replication fork initiated at the other side of the palindrome arrives to promote termination (Zhang, et al. 1997). Interestingly, this central barrier element is required for both proper excision of the rDNA before amplification in the macronucleus, as well as for maintaining genetic stability at the unamplified rDNA gene in the micronucleus (Yakisich & Kapler, 2006). In the absence of the barrier element breakage occurs at the loci leading to loss of the chromosome arm, which again has a dominant effect on the stability of the homologues chromosome present in the diploid nucleus.
\n\t\t\tSimilarly, developmentally regulated replication barriers have been described in X. laevis. Firstly, a barrier is present at the RNA polymerase I termination region. This barrier can be detected in cell culture and tissues where the rDNA is highly transcribed, but not in early embryos and in egg extracts where transcription is low or absent (Hyrien & Mechali, 1993; Wiesendanger, et al. 1994; Hyrien, et al. 1995). Secondly, 15 weaker pause sites distributed over the rDNA unit appear during the midgastrula stage, for then to disappear again at the neurula stage (Maric, et al. 1999). The appearance of these pause sites was proposed to reflect chromatin remodelling associated with the developmental regulation of polymerase I transcription.
\n\t\t\tThe replication barrier in the rDNA of S. cerevisiae was the first to be described (Brewer & Fangman, 1987; Linskens & Huberman, 1988). Like the other barriers it is located in one of two NTS regions downstream of both the coding regions of the polymerase I transcribed 35S rRNA and the RNA polymerase III transcribed 5S rRNA. However, unlike the other eukaryotic systems, the barrier activity is not mediated by the Reb1 factor involved in Polymerase I transcription termination (S. cerevisiae Reb1 is related to Mammalian TTF1 and S. pombe Reb1; see below) (Reeder, et al. 1999). Instead the barrier activity is mediated by an unrelated S. cerevisiae factor Fob1 that binds to the DNA at a region closer to the origin (Kobayashi & Horiuchi, 1996) and about 90% of replication forks are stalled at this barrier (Brewer et al. 1992). Barrier activity is independent of transcription (Brewer, et al. 1992) and Fob1 interacts with three sites, RFB1-3, where the latter two are the minor barrier sites (Brewer, et al. 1992; Gruber, et al. 2000; Ward, et al. 2000; Kobayashi, 2003). The cis-acting sequences show phylogenetic conservation between Saccharomyces species (Ganley, et al. 2005). Fob1 possesses a Zn2+-finger domain and a domain with similarity to integrases (Dlakic, 2002); mutations in the former affect DNA binding activity, barrier activity and HOT1 (HOT1 is a recombination hot spot in the rDNA) activity, whilst a mutation of the putative catalytic residue D291A of the integrase domain has no effect (Kobayashi, 2003). Using Atomic Force Microscopy (AFM) it was shown that Fob1 interacts with the barrier sequence in a fashion where the DNA is wound around the protein (Kobayashi, 2003). Moreover, the same data suggest that Fob1 acts as a dimer interacting with two sequences at the same time. The position of the stalled replication fork has been precisely mapped (Gruber, et al. 2000); the 3’ end of the leading-strand and the 5’ end of the lagging-strand map three nucleotides apart, 41 and 38 nucleotides in front of the sequences required for pausing at RFB1, respectively. However, weaker signals due to fork stalling were also observed in a region between RFB1 and RFB2 (Figure 1).
\n\t\t\t\tPositions of the sites of replication stalling for the S. cerevisiae rDNA barrier. Positions of stalling of the leading-strand polymerase (red arrows) and 5’-ends of the last lagging-strand Okazaki fragment (blue arrows) are shown relative to the binding sites of Fob1.
AFM analysis also shows that the RNA primer at the lagging-strand has been removed in the stalled replication complex. (Kobayashi, 2003). Stalling of the replication fork at the Fob1 barrier depends on Tof1 (S. pombe Swi1/Human TIMELESS) and Csm3 (S. pombe Swi3/ Human TIPIN), but not Mrc1 (S. pombe Mrc1/ Human Claspin) (Mohanty, et al. 2006). When the replication fork is stalled at the Fob1 barrier located at an ectopic site (Calzada, et al. 2005) the replisome (Mrc1, Tof1, MCM-Cdc45, GINS and DNA polymerases α and ε) is maintained intact, thus allowing the replication fork to restart. The stability of the stalled replication fork was also shown not to depend on replication checkpoint kinases Mec1 and Rad53 or the Sml1 factor (See Section 6.0), nor does the replication restart depend on the Rad52 recombinase. Stalling leads to the recruitment of the Rrm3 helicase, which was suggested to mediate restart. These data and suggestions were later verified by a study that showed that replication stalling was dependent on Tof1 and Csm3, but partly restored in Δtof1 Δrrm3 and Δcsm3 Δrrm3 mutants (Mohanty, et al. 2006). It was proposed that Tof1 and Csm3 mediate stalling by counteracting Rrm3, but since Rrm3 is required for efficient replication past many non-histone DNA binding proteins (See Section 10.0), the effect could be unspecific (Mohanty, et al. 2006). Similarly, the requirement for two other helicases, Sgs1 and Srs2, was tested in the absence of Tof1 but neither affected barrier activity. Another study looked at Sgs1, Top3, Dnl4 and Rad52 with again no major effects on barrier activity, although in all the mutants there was an increase in the amount of single-stranded DNA at the fork measured using electron microscopy (Fritsch, et al. 2010). However, increased barrier activity was observed in a Dna2 mutant, a helicase implicated in Okazaki fragment maturation, suggesting that events at the lagging strand affect the stalled fork (Weitao, et al. 2003a; Weitao, et al. 2003b). The biological function of the Fob1 barrier has been an area of intense research and resulted in some key findings. Firstly, Fob1 barrier activity promotes recombination between repeats in the rDNA array and has a role in repeat expansion through induction of recombination and unequal sister-chromatid exchange (Kobayashi & Horiuchi, 1996; Kobayashi, et al. 1998; Mayan-Santos, et al. 2008; Ganley, et al. 2009). Double stranded breaks have been detected at the barrier and related to replication fork pausing, potentially due to fork collapse (Weitao, et al. 2003a; Weitao, et al. 2003b; Fritsch, et al. 2010). Secondly, barrier activity acts to prevent collisions between the DNA replication fork and the polymerase I transcription forks, leading to fluctuations in copy numbers and formation of extra chromosomal rDNA circles (ERCs) (Takeuchi, et al. 2003). Thirdly, Fob1 barrier activity has also been implicated in ageing as its fork barrier activity leads to formation of ERCs that accumulate in the mother cell, as well as in an increased loss of heterozygosity of markers distal to the rDNA array on chromosome XII (Defossez, et al. 1999; Lindstrom, et al. 2011). However, recent data suggest that age related replication stress underlies the ageing process, and not the formation of ERCs (Lindstrom, et al. 2011). Forthly, Fob1 also has a role in silencing of the rDNA through the recruitment of the regulator of nucleolar silencing and telophase exit (RENT) complex that includes Net1, Sir2, CDC14, Tof2, Lrs4 and Csm1 as well as Cohesin (Huang & Moazed, 2003), but this role is independent of the replication barrier activity of the protein (Bairwa, et al. 2010). The RENT complex inhibits polymerase II transcription and represses recombination (Kobayashi, et al. 2004; Kobayashi & Ganley, 2005). Lastly, Fob1 also regulates the activity of Topoisomerase I, as Fob1 dependent but replication independent topoisomerase I catalysed nicks have been mapped within the replication barrier region (Burkhalter & Sogo, 2004; Di Felice, et al. 2005).
\n\t\t\tReplication barriers have also been identified in human and mouse rDNA arrays (Little, et al. 1993b; Langst, et al. 1998; Lopez-estrano, et al. 1998b). The barrier signals were detected by 2D-gel analysis of replication intermediates and map to the binding sites of the TTF-I transcription factor within the NTS region located downstream of the 38S rRNA polymerase I transcribed regions. The TTF-1 transcription factor belongs to the same family of proteins as S. pombe Rtf1 and Reb1 and S. cerevisiae Reb1 (see Figure 2). TTF-I mediates termination of polymerase I transcription, but also has additional roles in polymerase II termination as well as both polymerase I transcription activation and silencing (Langst, et al. 1998; Wang & Warner, 1998). TTF-I binds to ten 18 base-pair long or eleven 11 base-pair long Sal-boxes in mouse and human cells, respectively, which are located within the NTS region of the rDNA. TTF-I binding mediates polar polymerase I transcription termination (Grummt, et al. 1985a; Grummt, et al. 1985b; Lang, et al. 1994; Reeder & Lang, 1994). However, TTF-I Sal-box binding also promotes replication barrier activity. 2D-gel analysis of replication intermediates isolated from the human cell cultures suggests that the rDNA replication barriers are bi-polar, stalling forks moving in both directions (Little, et al. 1993a). A similar analysis of the mouse barriers showed that in this system the TTF-I dependent barriers are polar, mediating replication stalling at each of the four clusters of Sal-boxes of replication forks moving in the opposite direction to that of the flanking RNA polymerase I transcription (Lopez-estrano, et al. 1998a). Finally, an in vitro study suggests that only Sal-box 2 acts as a strong replication barrier (Gerber, et al. 1997). Using the SV40 in vitro\n\t\t\t\t
\n\t\t\t\t\n\t\t\t\tProtein domains and DNA interaction sequences of the related TTF-I, Reb1 and Rtf1 factors. Left, the positions of the structural myb DNA-binding motifs identified by a hidden Markov model analysis are shown (Eydmann, et al. 2008); Domains with defined functions are indicated by square horizontal brackets. The position of the Rtf1-S154L mutation that changes the polarity of the RTS1 element is indicated in red. Right, DNA recognition sequences of Reb1 and Rtf1 and Human/Mouse TTF-I.
replication system, this study also defined the Sal-box 2 cis-acting sequence requirements for site-specific replication termination, and verified the TTF-I dependence for barrier activity. When bound to Sal-box 2, TTF-I counteracts the strand displacement activity of the SV40 large-T antigen 3’-5’ helicase (Putter & Grummt, 2002b). Three cis-acting elements are required for full activity of Sal-box 2. Firstly, the in vitro barrier activity depends on the Sal-box 2 sequences that mediate TTF-I binding (Grummt, et al. 1985a; Putter & Grummt, 2002b). Secondly, this binding site is flanked by a GC-rich box that consists of 20 cytosine residues followed by a GC-rich stretch at the origin-proximal side. Introduction of point mutations within this region, shortening the stretch of cytosines (dC stretch), or inverting this region relatively to the Sal-box, abolished replication barrier activity and contra-helicase activities (Gerber, et al. 1997; Putter & Grummt, 2002a). The 20 base pair long dC stretch potentially forms a secondary structure, a poly dG-dG-dC triple helix that can act as a barrier for the progressing helicase or polymerase (Putter & Grummt, 2002a). Thirdly, flanking the GC rich sequence is a stretch of 26 thymidines that acts as an enhancer of the barrier activity; deletion of the thymidines causes a ~30% reduction in activity (Putter & Grummt, 2002a). The position of the in vitro leading-strand replication termination site has been mapped to 28 nucleotides from the Sal-box just in front of the long stretch of dC residues (Gerber, et al. 1997).
\n\t\t\t\tSeveral studies of the 883 amino acid long TTF-I factor have been performed. Two regions within the protein have been implicated in polymerization of the protein (Sander, et al. 1996a; Gerber, et al. 1997), (Figure 2). A 323 N-terminal truncated version of TTF-I is fully active for both in vitro transcription and replication termination, while a 445 amino acids N-terminal truncation leads to loss of both activities. Neither of these truncations affect the DNA binding of the protein, however, the region between residue 323 and 445 is required for polymeric TTF-1 to interact simultaneously with two DNA sites (Sander & Grummt, 1997; Evers & Grummt, 1995; Sander, et al. 1996b; Gerber, et al. 1997). Similar to the other replication barriers described below, the data suggest that passive binding of TTF-1 is not sufficient to cause replication barrier activity, but that in addition specific interactions with replication fork proteins must occur. Furthermore, dimerization or polymerization of TTF-I might be important for replication termination as observed recently for S. pombe Reb1 (see 3.6). Interestingly, TTF-I binds both in the promoter region and, as described above, in the transcription termination region of the polymerase I transcribed element, and a 3C analysis shows that these two regions interact by a mechanism that depends on TTF-I (Nemeth, et al. 2008). This interaction has been proposed to be important for regulation of transcription initiation; TTF-1 recruits the chromatin remodelling complex NoRC to the promoter region through a direct interaction in the N-terminal part of TTF-I to silence rDNA transcription (Nemeth, et al. 2004). The N-terminal domain of TTF-I has a negative effect on DNA binding through an interaction with the DNA binding domain. This inhibition is relieved through the interaction in trans with NoRC (Nemeth, et al. 2004). The described interaction between TTF-I molecules bound at the promoter and termination regions, also opens up the possibility that there might be coordination between transcription initiation at the promoter and replication barrier activity at the transcription termination region.
\n\t\t\t\tThe proteins Ku70 and Ku86 have also been implicated in replication barrier activity at the mammalian rDNA (Wallisch, et al. 2002). Using affinity purification with a bait that consisted of the GC-rich region that flanks the Sal\n\t\t\t\t\tbox 2, a protein fraction was isolated which stimulated in vitro replication termination. The stimulating activity could be depleted from the HeLa cell extracts using an oligonucleotide sequence containing the GC rich region bound to DYNA beads, and subsequently the depleted extracts could be complemented by addition of recombinant Ku70/Ku86. Thus, Ku70/Ku86 binding promotes replication termination at the Sal-box 2, potentially involving the formation of secondary structures when the DNA is unwound by the helicase or replicated by the polymerase.
\n\t\t\tThe rDNA barrier region of S. pombe is more complex than the other systems described, in that four different barrier elements have been defined; RBF1-4. These barrier elements are clustered downstream of the coding region of the 25S rRNA gene in the NTS. Again the elements act as polar barriers for replication forks initiated at the origin and moving toward the RNA polymerase I transcribed unit, thus preventing collisions between the two types of enzymatic complexes. Two different trans-acting factors have been identified that serve as barriers at these sites, Reb1 and Sap1.
\n\t\t\t\tSap1 is responsible for the barrier activity at the RFB1 site, which in one study was delineated to a 21 bp region (Krings & Bastia, 2005) and in another to a 30 bp region (Mejia-Ramirez, et al. 2005). Sap1 is an essential DNA binding protein involved in chromatin formation, checkpoint activation and maintenance of genome stability (Arcangioli & Klar, 1991; Ghazvini, et al. 1995; de Lahondes, et al. 2003; Noguchi & Noguchi, 2007). Loss of Sap1 causes chromosomal segregation defects, while overexpression causes toxic DNA replication dependent chromosome fragmentation and abnormal mitosis. Due to the fact that Sap1 is essential, the evidence for Sap1 binding at the RFB1 site is indirect. Firstly, Sap1 was purified from crude extracts as a factor that binds the cis-acting sequences at RFB1 (Mejia-Ramirez, et al. 2005). Secondly, RFB1 point mutations that affect Sap1 binding in vitro also affect barrier activity in vivo (Krings & Bastia, 2005). Lastly, supershifts can be achieved with antibodies against tagged-Sap1 in EMSA experiments (Krings & Bastia, 2005). Binding of the dimeric Sap1 protein to the RFB1 site causes a slight bending of the DNA in vitro (Krings & Bastia, 2005). Replication fork stalling at RFB1 is dependent of the trans-acting factors Swi1 and Swi3 (Mejia-Ramirez, et al. 2005). Sap1 also binds the SAS1 sequence required for mating-type switching (Arcangioli & Klar, 1991), but does not cause barrier activity at this locus (Kaykov, et al. 2004; Krings & Bastia, 2005; see Section 8.1). A comparison of the interactions between Sap1 and these two cis-acting sequences showed that the Sap1 dimer bound differently to the two sites; the interaction of the Sap1 protein with RFB1 covered successive major grooves, had translational symmetry and occurred with higher affinity; while the interaction with SAS1 was a minor groove interaction, occurred with a relatively lower affinity and had rotational symmetry (Krings & Bastia, 2006).
\n\t\t\t\tReb1 was identified as mediating barrier activity at the two cis-acting sites RFB2 and RFB3 (Sanchez-Gorostiaga, et al. 2004). Reb1 also mediates Polymerase I termination at the same sequences (Melekhovets, et al. 1997). Reb1 belongs to the same family of factors as Human/Mouse TTF1, S. cerevisiae Reb1 and S. pombe Rtf1, which are characterized by the presence of a repeated myb domain (Eydmann, et al. 2008) Figure 2). Reb1 acts as a dimer that dimerizes through a 146 amino acid long N-terminal domain (Biswas & Bastia, 2008). This dimerization allows the dimeric protein to interact with two recognition sites at the same time (Singh, et al. 2010). When the two sites are in cis the intervening DNA is looped out, however, the dimeric protein can also interact with two sites in trans. In the latter case, “chromosome kissing” was observed between a Reb1 dependent barrier on chromosome 2, Ter344314, and two sites on chromosome 1, Ter4257637 (Cyp8) and Ter4680236 (Srw1/Ste9) (Singh, et al. 2010). Furthermore, using weakened binding sites at the Ter344314 and Ter4680236 sites it was shown that this “chromosome kissing” was important for barrier activity. Only the middle 156-418 AA Section of Reb1 is absolutely required for barrier activity. Barrier activity at RFB2 and RFB3 depends on both Swi1 and Swi3, however, a Swi1 mutation (swi1-rtf) that abolishes barrier activity at the RTS1 element does not affect barrier activity at the RFB1-4 (see Section 8.0; Krings & Bastia, 2004). Interestingly, when the 156-418 AA Reb1 segment was expressed in S. cerevisia, it was unable to act as a barrier even though it was binding to the RFB3 sequence (Biswas and Bastia, 2008). Finally, Reb1 has also been shown to be important for gene regulation; Reb1 binding at the promoter of Ste9 is required for transcriptional activation and G1 arrest (Rodriguez-Sanchez, et al. 2011). Reb1 also acts as a replication barrier at this site.
\n\t\t\t\tThe RFB4 barrier is the weakest of the four barriers, and has been proposed to be generated by collisions between the polymerase I transcription machinery and the DNA replication machinery (Krings & Bastia, 2004). The intensity of the RFB4 barrier signal increases in the absence of Swi1, Swi3 or Reb1, potentially because more replication forks are colliding with the transcription machinery. Also, RFB4 does not act as a replication barrier when the region is moved onto a plasmid.
\n\t\t\tReplication pause sites have been described at both the S. cerevisiae telomeres and centromeres. At the Y’ elements of the telomeres the replication fork pauses at internal C1-3A/TG1-3 telomeric sequences as well as at the terminal C1-3A/TG1-3 repeats. The internal C1-3A/TG1-3 sequences promote stalling independent of the orientation relative to of the progressing replication fork, and the replication pausing is intensified in absence of the Rrm3 helicase (Ivessa, et al. 2002; Makovets, et al. 2004, Makovets, 2009). In the rrm3 mutant strain, pausing can also be observed at an inactive ARS element in the subtelomeric region. Insertion of Tetrahymena telomeric repeats in the subtelomeric region of S. cerevisiae did not lead to pausing suggesting that it is the binding of a trans-acting factor that leads to the barrier activity and not the repeat sequences themselves (Makovets, et al. 2004). However, mutation of the sub-telomeric binding sites of Tbf1 and Reb1, deletion of the Rif1, Rif2, Sir2 or Sir3 genes, or introduction of a C-terminal truncated version of Rap1, do not affect the replication pause (Makovets, et al. 2004; Makovets, 2009). Tbf1 and Reb1 act at chromatin barriers in the subtelomeric region, while Sir2 mediates silencing at the telomeres and Rap1 binds directly the telomeric repeats when they are double stranded. The C-terminal truncated version of Rap1 is unable to interact with the Rif proteins and deficient in the recruitment of Sir proteins to the telomeres, although DNA binding to the telomeric repeats is unaffected. Thus, it is argued that it is most likely Rap1 binding per se, potentially through the interaction with other unknown protein(s), which mediate the pause activity. Since the strength of the replication pause is dependent on the length of the telomeres, a potential role of the pause is to regulate the time in which the telomeres can be elongated; short telomeres do not cause pausing and are therefore replicated faster, thus giving telomerase longer time for elongation.
\n\t\t\tSeveral replication pause sites have also been observed at the sub-telomeric regions of S. pombe, however, it is not known what proteins mediate pausing at these sites (Miller, et al. 2006). In addition, a protein that binds the telomeric repeats, named Taz1, has been attributed an interesting role; in the absence of Taz1 replication defects are observed at the telomeric repeats, leading to loss of telomeric sequences and chromosome entanglement. In addition, in the absence of Taz1, replication pausing is observed at the junction between the telomeric repeats and the sub-telomeric region, as well as at repeats located internally within the chromosome. In the latter case, the requirement is independent of the orientation of the repetitive sequence (Miller, et al. 2006). One possibility is that Taz1 has a role in recruiting replicative helicases that act to aid fork progression through the repeats. With respect to this, it is interesting to note that the human homologues of Taz1, TRF1 and TRF2, have also been shown to affect telomeric replication, although in a different manner (Ohki & Ishikawa, 2004). Using the SV40 in vitro replication system, it was shown that addition of recombinant TRF1 and TRF2 lead to stalling of the replication fork at the telomeric region of the linear SV40 DNA. Similarly, overexpression of TRF1 in HeLa cells, leads to an increase of replication foci that overlap with telomeric signals, suggesting an increase of replication forks stalled at telomeres.
\n\t\t\tReplication pausing is also observed at the S. cerevisiae centromeres CEN1, CEN3 and CEN4, and presumably replication pausing occurs at all centromeres (Greenfeder & Newlon, 1992). Interestingly, pausing at the centromeric DNA is bipolar and thus occurs independently of the direction by which the replication fork enters the centromeric DNA. A mutational analysis of the cis-acting sequences showed that the barrier activity is dependent on the ability of the centromeric DNA to form a nuclease resistant core protein structure, suggesting that it is the interaction with centromeric proteins that causes the pause to replication fork progression (Greenfeder & Newlon, 1992). It is not known whether replication pausing is important for centromere function. Interestingly, recent papers describing the genome-wide localization of phosphorylated histone H2A show accumulation at the centromeric regions of both S. cerevisiae and S. pombe, thus, potentially replication stalling occurs at centromeres in both yeasts (see Section 11.0).
\n\t\tEarly work identified replication pause sites at Ty1-LTRs and tRNA genes in S. cerevisiae (Greenfeder & Newlon, 1992, Deshpande & Newlon, 1996). These tRNA gene replication barrier activities were shown to be polar only stalling replication forks moving in one direction, that opposite to the direction of Polymerase III transcription. Cis- and trans-acting mutations that reduce or abolish the efficiency of transcription initiation correspondingly reduced or abolished replication barrier activity. Indeed, a temperature sensitive mutation in the large subunit of RNA polIII, that affects transcription initiation but not the formation of the initiation complex consisting of TFIIIC and TFIIIB at the tRNA gene also abolished barrier activity. Therefore, the replication barrier activity most likely results from a direct interaction between the transcription machinery and the progressing replication fork complex, although a build up of supercoiling between the approaching transcription and replication forks was also proposed as a potential mechanism for fork pausing (Deshpande & Newlon, 1996). Importantly, a later study showed that barrier activity is abolished in a Δtof1 mutant (S. pombe Swi1/Human TIMELESS), but is restored in the Δtof1\n\t\t\t\tΔrrm3 double mutant (Mohanty, et al. 2006). In the same study, increased stalling was observed at the tRNA gene in the absence of the Rrm3 helicase.
\n\t\t\t\n\t\t\t\tS. pombe tRNA\n\t\t\t\t\tGLU\n\t\t\t\t and sup3-e tRNA genes have also been shown to pause replication forks. However, in this system the tRNAs act as bi-polar barriers stalling replication forks moving in both orientations. Furthermore, the tRNA gene barrier activity is independent of Swi1 function (McFarlane & Whitehall, 2009; Pryce, et al. 2009). Similarly, polar replication pausing has been observed at S. pombe retrotransposons Tf2 LTRs (Zaratiegui, et al. 2011). Interestingly, replication pausing at these elements is abolished by the sap1-c mutation. The sap1-c allele was isolated as a spontaneous mutation that restored growth and improves viability to a double mutant strain of the two CENP-B homologues Abp1 and Cbh1. The Δabp1\n\t\t\t\tΔcbh1 double mutant has poor viability due to increased levels of unreplicated regions and/or recombination structures, and the sap1-c allele was isolated as a spontaneous mutation that restored growth and viability. The sap1-c mutation reduces the Sap1 proteins ability to bind DNA. Thus, Abp1 and Cbh1 have roles preventing genetic instability and replication defects induced by Sap1 barrier activity. Δabp1 and Δcbh1 single mutants slightly increase the intensity of the Sap1 dependent barrier signal, and in the Δabp1 Δcbh1 double mutant recombination intermediates can also be observed by 2D-gel analysis of replication intermediates (Zaratiegui, et al. 2011). Abp1 also localizes to tRNA genes suggesting that it might have a role in maintaining genome stability at these replication barriers as well. Abp1 interacts with Mcm10 that has been shown to have primase activity (Locovei, et al. 2006), thus Abp1 might promote replication restart after pausing through a priming event.
\n\t\tReplication slow zones have been described in S. cerevisiae and are characterized by increased amounts of replication intermediates as measured by 2D-gel analysis (Cha & Kleckner, 2002). These zones are regularly spaced throughout the genome between active origins, except at the centromere. The replication slow zones were identified as regions of genetic instability in the mec1 mutant background. Mec1 is the homologue of Human ATR and S. pombe Rad3, and has multiple roles in DNA replication, replication checkpoint activation, DNA damage repair and recombination. Interestingly, the genetic instability is suppressed by a Δsml1 mutation, suggesting that the instability is due to low levels of dNTPs. Sml1 is an inhibitor of ribonucleotide reductase, and the lack of Sml1 leads to an increase in dNTP levels. Similarly, the Δrrm3 mutation partly suppresses the genetic instability observed at replication slow zones, which is correlated with a decrease in the Sml1 protein level (Hashash, et al. 2011). Thus, the data suggest that low levels of dNTPs cause replication forks to slow down even in an unperturbed S-phase, and that Mec1 is important for maintaining the stability of these slow moving forks, potentially via the function of Mec1 in regulating the nucleotide pools through inhibition of Sml1 and in intra-S and G2-M checkpoint activation. Whether replication slow zones are important for genome stability in higher organism has yet to be established.
\n\t\tInverted repeats and micro repeats, through formation of triplexes and G-quartets have all been shown to inhibit DNA polymerase progression in vitro (for a review see Mirkin & Mirkin, 2007). Similarly, there is growing in vivo evidence that structures and repetitive sequences in the DNA are difficult templates, which promote replication fork stalling and as a consequence genetic instability. Since formation of structures distinct to the double helix are not energetically favoured, especially in front of the replication fork where there is supercoiling, it is most likely that the structures are formed in the lagging-strand template (Mirkin & Mirkin, 2007). Sequences that have been shown to mediate fork stalling include inverted repeats as well as (CAG)n/(CTG)n, (CGG)n/(CCG)n, and (GAA)n/(TTC)n repeat sequences. In the case of the inverted repeats, a very elegant recent study showed that while two Alu sequences oriented as direct repeats did not affect replication fork progression, the same sequences oriented as inverted repeats caused fork stalling in E. coli, S. cerevisiae and a mammalian cell line (Voineagu, et al. 2008). In E. coli and the mammalian cell lines the ability of the inverted repeats to mediate stalling was dependent on the homology between the inverted sequences, and it gradually decreased with decreasing homology, thus supporting the idea that structures formed at the sequences were responsible for the pause. Furthermore, by varying the distance between the inverted sequences the authors were able to show they were most likely due to formation of hairpins in the lagging-strand template and not by cruciforms formed in front of the replication fork. The foundation of this conclusion was the fact that similar barrier activity was observed even in the presence of a 12 bp spacer, which would either reduce or abolish the ability of the repeated sequence to form a cruciform structure. Interestingly, S. cerevisiae Tof1 and Mrc1 (homologues of S. pombe Swi1 and Mrc1 and Human Timeless and Claspin) are required for efficient passage through the repeats and mutation of these factors leads to an increase in the intensity of the replication pause signal, an effect which is opposite to that observed at protein-mediated barriers. The repetitive sequences d(CGG)n, d(CCG)n d(CTG) and d(CAG) are also thought to form hairpin structures with both Watson-Crick and nonWatson-Crick base pairs, and d(CGG) sequences can form quartets (Chen, et al. 1995, Gacy, et al. 1995, Zheng, et al. 1996, Mariappan, et al. 1998). Both (CAG)n/(CTG)n and (CGG)n/(CCG)n repeats have been shown to stall replication forks in S. cerevisiae and mammalian cells, while (GAA)n/(TTC)n have been shown to stall forks in S. cerevisiae (Pelletier, et al. 2003; Krasilnikova & Mirkin; 2004a, Krasilnikova & Mirkin, 2004b; Kim, et al. 2008). The barrier activity was length dependent, although there were differences between systems; 10 (CGG)/(CCG) repeats were sufficient to stall replication forks in S. cerevisiae but 40 were required in mammalian cells (Voineagu, et al. 2009). Similarly, 60 (GAA)/(TTC) repeats do not cause any barrier activity, while increased barrier activity can be observed with increasing number of repeats (120, 230 and 340 units). There are also variations in whether the orientation of the repetitive sequences are important for barrier activity; in S. cerevisiae (GAA)n/(TTC)n barrier activity is orientation-dependent, whilst (CGG)n/(CCG)n repeats pause the replication fork in both orientations (Pelletier, et al. 2003; Kim, et al. 2008): In mammalian cells (CGG)n/(CCG)n repeats act as a barrier in both orientations (Voineagu, et al. 2009). Again, both S. cerevisiae factors Tof1 and Mrc1 were required for efficient replication through the repeat sequences as observed for an inverted repeat. Interestingly, a mutant Mrc1 protein (Mrc1AQ) that can not be phosphorylated by the checkpoint kinases did not affect the barrier activity, thus the authors concluded that it is not the checkpoint function of Mrc1, but this factor’s role in stabilizing stalled replication forks that is required (Voineagu, et al. 2009). Instability of stalled replication forks at repeat sequences is thought to underlie a range of Human diseases including fragile X-syndrome, Fraxe, Huntinton’s disease and myotonic dystrophy (reviewed in Pearson, et al. 2005).
\n\t\tIn the fission yeast S. pombe, a program of mating-type switching is mediated by a replication-coupled recombination event. Three different replication barriers are involved in setting up this cellular program of differentiation, where the expressed mating-type specific cassette at the mat1 locus is replaced with a gene cassette expressing the information of the opposite mating-type. The information is copied from one of the two transcriptionally silenced centromere-distally located donor loci,\n\t\t\t\tmat2P and mat3M, into to the expressed mat1 locus. In order for this program of cellular differentiation to occur, the mat1 locus has to be replicated in a centromere-distal direction. The unidirectional replication of the mat1 locus is maintained by the RTS1 element, which is located at the centromere-proximal side of mat1 and which acts as a polar replication terminator. Replication forks that move in the centromere-distal direction are terminated at the RTS1 element, while forks moving in the centromere-proximal direction are allowed to pass through unhindered (Dalgaard & Klar, 2001). At the sequence level the RTS1 element consists of two cis-acting regions that cooperate for function (Codlin & Dalgaard, 2003); a 446 base pair region named region B that contains four repeated ~55 bp long motifs as well as a 64 bp enhancer region called region A of similar length. Each of the repeated motifs of region B contributes to the overall barrier activity. A linker substitution analysis of region-B-motif-4 established that only a 20 bp region within the 55 bp long repeat is required for activity. This 20 base pair region shows similarity to the S. pombe Reb1 recognition site (Figure 2). Region A on the other hand is characterized by an uneven distribution of purines and pyrimidines on the two strands. In the absence of region A, the presence of each of the repeated motifs of region B has an additive effect on overall barrier activity. In the presence of region A, the region B motifs cooperate for function leading to a four-fold increase in overall barrier activity. Individually, region A does not possess any barrier activity. A recent study showed that the factor Sap1 binds to the enhancer region A (Zaratiegui, et al. 2011), however, it is not known whether Sap1 binding contributes to enhancer activity. Several factors have been identified that are required for efficient replication termination at the RTS1 element. Rtf1 is a member of the family of factors that include S. cerevisiae Reb1, S. pombe Reb1 and human/mouse TTF-I (Eydmann, et al. 2008, see Sections 3.4 & 3.5; Figure 2). Deletion of the rtf1 gene abolishes RTS1 barrier activity. This protein family is characterized by the presence of two myb-domains that respectively contain three and two myb DNA interacting motifs. Each of the two Rtf1-myb domains have been expressed and purified separately and have been shown to have DNA binding activity; Rtf1-domain I binds RTS1 DNA in vitro, interacting both with the repeated motifs of region B and the enhancer region A (Eydmann, et al. 2008). The Kd for the interaction with region A is 3467 nM, while the interaction with the repeated motif is somewhat stronger with a Kd for the interaction at 549 nM. A ten base pair substitution that abolishes barrier activity of the region B motif 4 in vivo strongly reduces binding of the Rtf1-domain I in vitro. Rtf1-domain II on the other hand only interacts weakly with the region B motif 4. A 10 bp substitution of the region flanking the binding site of domain I, that abolishes barrier activity of motif 4 in vivo, also abolishes binding of the Rtf1-domain II in vitro. Amino acid substitutions have been identified in both Rtf1-domain I and II that abolish barrier function, establishing genetically that they are of functional importance (Eydmann, et al. 2008). In addition, a point mutation has been identified in Rtf1-domain I (S154L) that changes the polarity of the RTS1 barrier, such that instead of terminating replication forks moving in the centromere-distal direction, it acts as a pause site for replication forks moving in the centromere-proximal direction. The Rtf1-domain I-S154L mutation slightly enhances the domain affinity for region A and motif 4, such that the Kd is now 343 nM for region A and 265 nM for the motif 4. This observation suggests that the Rtf1-S154L protein is binding the RTS1 element, but that it is unable to stall the replication fork, thus a protein-protein interaction(s) between Rtf1 and the progressing replication fork may be important for barrier activity. In addition, a dominant Rtf1-mutation has been identified that abolishes termination of replication. This non-sense mutation truncates the Rtf1 protein such that 120 amino acids of the C-terminus are missing. Two-hybrid analysis of this 120 AA C-terminal Rtf1 tail shows that it can interact with itself. This discovery suggests that Rtf1 self-interactions are required for barrier activity and that the tail-less Rtf1 allele interferes with the action of the wild-type protein at RTS1 (Eydmann, et al. 2008).
\n\t\t\tIn addition to DNA binding proteins other factors have been shown to be required for RTS1 function (Inagawa, et al. 2009). Rtf2 is required for efficient termination of DNA replication at the RTS1 element. An epistasis analysis of the enhancer region A deletion and the Δrft2 mutation suggest that Rtf2 acts through the region A deletion. In the absence of Rtf2 replication forks pause in an Rtf1-dependent manner, but are restarted again. This replication restart is dependent on the Srs2 helicase, but not the Rqh1 helicase. Potentially, Srs2 acts by removing Rtf1 from the DNA in front of the replication fork, in a manner similar to its role in preventing recombination by removing Rhp51/Rad51 from single-stranded DNA (Krejci, et al. 2003; Veaute, et al. 2003). Rtf2 is the defining member of a family of proteins that are conserved from S. pombe to humans, which are characterized by the presence of a novel type of C2HC2 ring finger motif that potentially only binds one Zn2+ atom. A similar Ring finger motif, named the SP motif, with only one Zn2+-atom binding site, is found in many E3 SUMO ligases including S. cerevisiae Siz1, Siz2; S. pombe Pli1, Nse2; human PIAS1, PIASxβ, PIAS3, PIASy, Mms21 (Watts, et al. 2007; Yunus & Lima, 2009) and an epistasis analysis suggests that Rtf2 and SUMO (pmt3) might act together in the same pathway (Inagawa, et al. 2009). However, Rtf2 also seems to have a role that is independent of SUMO, as slow moving replication forks are present at the RTS1 element in the Rtf2 single mutant that are absent in the SUMO single mutant. In addition, Rtf2 interacts with proliferating cell nuclear antigen (PCNA) and might be travelling with the replication fork. Sumorylation and ubiquitination of PCNA at residues K127 and K164 has in S. cerevisiae been shown to affect molecular events at stalled forks (Stelter & Ulrich, 2003). Of these residues only K164 is conserved in S. pombe PCNA (gene pcn1). Interestingly, when lysine K164 is mutated to an alanine, it has no effect on barrier activity measured by genetic assays, which utilize efficiency of sporulation as the readout (Figure 3B). Thus most likely, Rtf2 targets either other residues of PCNA or other replication proteins for SUMOylation. Finally, both Swi1 and Swi3 are required for barrier activity at the RTS1 element (Dalgaard & Klar, 2000). Swi1 and Swi3 travel with the replication fork as part of the Replication Progression Complex (RPC) and genetic evidence suggests that Swi1 might interact directly with Rtf1 to mediate replication barrier activity; a point mutation in Swi1, swi1-rtf3 G2785A, has been identified that abolishes termination of RTS1 but does not affect other replication barriers such as the rDNA barrier and the mat1 pause site MPS1 (Dalgaard & Klar, 2000; Krings & Bastia, 2004). Recent work has demonstrated that in vitro the hetromeric complex of Swi1 and Swi3 can interact with double-stranded DNA (Tanaka, et al. 2010). In addition, a super-shift can be achieved through an interaction with purified Mrc1, a replication checkpoint protein that is also traveling with the RPC. Furthermore, data suggested that the swi1-rtf3 G2785A mutation affects the super-shift caused by Mrc1 binding, thus providing a possible mechanism for the loss of barrier activity at RTS1 (Tanaka, et al. 2010). However,
\n\t\t\tA. Comparison of the effect on barrier activity of the Δmrc1 mutation and the swi1-rtf mutation. The upper two panels show replication intermediates that have been digested with SacI and PstI and separated on a 2D-gel as described earlier. T is a termination signal, D the descending arc and P the pause signal. The analysed RTS1 element is present on a plasmid (pBZ142) (Method is described in Codlin & Dalgaard, 2003). Below, as comparison, the effect of the swi1-rtf mutation on the RTS1 element at it wild-type genomic position is shown (reproduced from (Dalgaard & Klar, 2000). B. Sporulation assays used for identifying effects on replication pausing at the MPS1 element (left two panels) and replication termination at the RTS1 element (right two panels). In the first case a reduction of replication pausing will lead to reduced sporulation, while in the second case reduced termination will lead to increased sporulation (For a description of the assay see Codlin & Dalgaard, 2003).
our analysis of a Δmrc1 strain shows that this mutation does not affect the overall RTS1 barrier activity, although the region of stalling does seem to be slightly expanded and the intensity of the descending arc is slightly more intense suggesting an increase of replication restart (Figure 3A). Thus, the swi1-rtf3 G2785A mutation must affect other protein-protein interactions required for barrier activity at RTS1, the most likely candidate for the interacting partner being Rtf1. A model for the possible mechanism of replication termination at RTS1 is given in Figure 4.
\n\t\t\tModel for the molecular mechanism of replication termination at the RTS1 element. Rtf1 molecules interact with the repeated motifs present in the RTS1 element as well as the enhancer region A. Potentially, C-terminal interactions of Rtf1 are important for stabilizing the interactions and can provide additional constraints when the DNA template is unwound by the approaching helicase. The function of the interaction of Sap1 with the enhancer region (region A) is unknown. When the replication complex approaches the RTS1 element, protein-protein interactions stall the progression. These protein-protein interactions are most likely between Rtf1-domain I and Swi1. The interactions potentially lead to inhibition of DNA unwinding by the MCM2-7 replicative helicase. The stalled replication fork is stabilized by the action of Rtf2, potentially by SUMOylation of other replication factors (Inagawa, et al. 2009).
Another replication barrier required for S. pombe mating-type switching is the MPS1 site required for imprinting at the mat1 locus (Dalgaard & Klar, 1999; Dalgaard & Klar, 2000; Vengrova & Dalgaard, 2004). mat1 imprinting is required for mating-type switching. At MPS1 the replication forks are paused but then all re-started again. All cis- and trans-acting mutations that abolish replication pausing at MPS1 also abolish imprinting, suggesting a mechanistic role between imprinting and replication pausing. Also, inversion of the mat1 locus relative to the RTS1 element so that it is replicated in the opposite orientation, abolishes both pausing and imprinting (Dalgaard & Klar, 1999). The cis-acting sequences that are required for pausing at the MPS1 are named the abc region (Sayrac, et al. 2011). Replication pausing can be observed both in P and M cells and interestingly the required sequences are located within the two Plus (P) and Minus (M) DNA cassettes that are swapped during the switching process (Dalgaard & Klar, 2000; Vengrova & Dalgaard, 2004). Thus, different cis-acting sequences mediate barrier activity in the two cell-types. Generally there is no sequence similarity between the P and M cassettes, however, within the abc region there is some sequence similarity (Sayrac, et al. 2011). The part of the abc region that is required for pausing is about 60 bp long and is located approximately 30 nucleotides from where the imprint is introduced. Both the P- and M-abc regions act as pause sites for the replication fork when they are located on a plasmid. Furthermore, competition experiments suggest that a trans-acting factor is binding to the abc region to mediate pausing; introduction of two multi-copy plasmids each containing 10 copies of the M- or P-abc regions cause a 30-40% reduction in sporulation (the sporulation efficiency is dependent on the efficiency of mating-type switching and mating). Importantly, the data does suggest that the factor(s) binding to the abc region is present in the cells in a significant number of molecules. Interestingly, the abc region does not mediate replication pausing at the transcriptionally silenced donor loci, even though mat2P is replicated in the correct orientation for pausing. This observation is important as it establishes a mechanism by which replication barriers can be regulated in other systems through the regulation of heterochromatin formation.
\n\t\t\t\tAs mentioned above, replication pausing at MPS1 is required for introduction of an imprint that marks switchable cells of S. pombe. This imprint has been shown to consist of two ribonucleotides incorporated into the DNA (Vengrova & Dalgaard, 2004; Vengrova & Dalgaard, 2005; Vengrova & Dalgaard, 2006). Several cis-acting regions have been identified that are required for the introduction of the imprint. First, there is a small cis-acting sequence located distal to mat1 that is named SAS1 (Arcangioli & Klar, 1991). SAS1 mediates binding of the trans-acting factor Sap1 that is required for barrier activity at the rDNA and LTRs (see Sections 3.6 & 5.0). However, the deletion of a 264 bp region (Msmt0) that includes SAS1 does not affect replication pausing at MPS1, suggesting that Sap1 has another role during imprinting (Dalgaard & Klar, 2000). A study of the interaction between Sap1 and its binding sites SAS1 and in the rDNA suggests that the protein might be interacting differently with the DNA at the two sites and that this might cause the difference in whether the protein mediates barrier activity (see Section 3.6). Another cis-acting sequence that is required for the introduction of the imprint is a 204 bp spacer region that is located centromere-proximal to the abc region and the site of imprinting (Sayrac, et al. 2011). Deletion of this region leads to abolishment of imprinting but only a small decrease in the intensity of the MPS1 signal. Replacing the region with a randomized sequence only has a small effect on both imprinting and pausing. Similarly, gradually reducing the length of the spacer region gradually reduces imprinting. High-resolution Southern blot analysis of replication intermediates from the strain carrying the spacer deletion mapped the position both of the 3’ end of the leading-strand and the 5’ end of the lagging-strand to the imprinting site, suggesting that the imprint consists of ribonucleotides that originate from the priming of an Okazaki fragment. Furthermore, the high-resolution Southern blot analysis also detected a centromere-proximal lagging-strand priming site about 350 nucleotides from the site of the imprint in the wild-type strain, which also previously has been detected by RIP mapping (Vengrova & Dalgaard, 2004; Sayrac, et al. 2011). This priming site is absent in the spacer deletion strain (instead a diffuse set of priming sites are observed closer to the imprint), but restored when the spacer is replaced by a random sequence (Sayrac, et al. 2011). The analysis also showed that while the sequences within the abc region are required, there is no sequence requirement for the region where the imprint is introduced. The data suggest that the imprint is formed in response to a site-specific priming event induced by replication pausing, and that the position of subsequent priming sites for subsequent replication fork restart is important for the formation of the imprint. Potentially, topological restraints could prevent access of factors if the priming site chosen after the release of the fork is too close to the imprinting site. This is the first example of a cis-acting region affecting the position of priming sites and suggests that chromatin could affect primer localization during lagging-strand replication. Importantly, the data provide a mechanism by which replication barriers can act to differentiate sister-chromatids for cellular differentiation.
\n\t\t\t\tThe mat1 imprint/ribonucleotides are maintained in the DNA for one cell-cycle, potentially through the binding of a trans-acting factor to flanking cis-acting sequences and act themselves as a replication barrier in the S-phase of the next cell-cycle (the 3’-end of the leading-strand was mapped to the nucleotide preceeding the ribonucleotides), thus leading to induction of the replication-coupled recombination event that drives mating-type switching (Vengrova & Dalgaard, 2004). Ribonucleotides have been shown to frequently be incorporated during DNA replication (Nick McElhinny, et al. 2010a; Nick McElhinny, et al. 2010b) and to stall DNA polymerases when present in the replication template in vitro (Vengrova & Dalgaard, 2004). Interestingly, only a single ribonucleotide present in a DNA template has been show to act as a barrier for DNA polymerase ε (Nick McElhinny, et al. 2010). However, RNA can template DNA repair in vivo and both S. cerevisiae polymerases α and δ can use templates containing four ribonucleotides in a row, although with decreased efficiency (Storici, et al. 2007).
\n\t\t\tIn S. cerevisiae, RNA polymerase II transcription has been shown to interfere with DNA replication fork progression. Transcription associated recombination (TAR) increased when the orientation of polymerase II transcribed genes was head-on to the progressing replication fork (Prado & Aguilera, 2005). Using cell-cycle specific promoters they also showed that this increase was dependent on the S-phase. The study also detected a replication barrier by 2D-gel analysis of replication intermediates within the recombination substrate that was dependent on polymerase II transcription. The intensity of the replication barrier signal was increased in an Rrm3 mutant. Importantly, more recent data suggest that it is the formation of RNA-DNA hybrids (R-loops) that are the cause of TAR and not the collision of the two types of forks (Aguilera & Gomez-Gonzalez, 2008; Gonzalez-Aguilera, et al. 2008). Also, several mutations affecting the maturation of mRNPs increase TAR. While these experiments were done using a CEN-plasmid, a genome wide study identified 96 sites where there were high levels of DNA polymerase binding (Azvolinsky, et al. 2009). A significant number of these were genes highly transcribed by RNA Polymerase II. However, there was no correlation between the direction of replication and transcription at these sites. The sites also correlated with high occupancy of the Rrm3 helicase, but the absence of Rrm3 did not lead to an increase in the DNA polymerase occupancy. Similarly, 2D-gel analysis of replication intermediates detected replication fork barriers at some of these sites, but the absence of Rrm3 did not lead to an increase in pausing at these barriers. R-loops have also been proposed to act as barriers for replication fork progression in human cells (Tuduri, et al. 2009; Tuduri, et al. 2010). Topoisomerase 1 (Top1) together with ASF/SF2, a splicing factor of the SR family, act to suppress the formation of DNA-RNA hybrids during transcription, thus preventing these R-loops from interfering with the progression of replication forks. In Top1 deficient cells γH2AX, a phosphorylated specialized histone (see Section 11.), accumulates at genes that are highly expressed during S-phase such as histone genes. The Top1 deficiency might affect fork progression in two ways; through Top1’s role in releasing super-coiling between two types of converging forks, and through Top1’s role in regulation of mRNP assembly, presumably by binding and phosphorylating splicing factors of the SR family (Rossi, et al. 1996; Soret, et al. 2003; Malanga, et al. 2008). It has long been known that in bacterial genomes highly-expressed genes are oriented such that transcription does not interfere with replication and it has been proposed that this might also be true for a large fraction of the human genome (Huvet, et al. 2007).
\n\t\tThe S. cerevisiae Rrm3 5’ to 3’ helicase has been shown to have an important function at replication barriers. Rrm3, which is a member of a family conserved from yeast to humans (Zhou, et al. 2002), was originally identified because its absence caused an increase in recombination and formation of extra chromosomal circles at the rDNA array (Keil & McWilliams, 1993; Ivessa, et al. 2000). Rrm3 travels with the replication fork, interacts in vivo with Pol2 (the catalytic subunit of DNA polymerase ε) and has a role in replication at all the yeast chromosomes (Azvolinsky, et al. 2006). Importantly, in the absence of Rrm3 replication pausing/stalling is observed (or increased) at an estimated 1400 sites in the genome, including centromeres, tRNA genes, inactive replication origins, and the silent mating-type loci, as well as telomeric and rDNA sites (Ivessa, et al. 2003). Potentially, Rrm3 is required for proper replication through all stable, non-nucleosomal protein-DNA complexes. Replication through the rDNA is generally impaired in a Δrrm3 mutant leading to replication stalling at several sites including the polymerase III transcribed 5S rRNA gene, at inactive origins and at the beginning and end of the RNA polymerase I transcription unit (Ivessa, et al. 2000). In addition, the intensity of the Fob1-dependent replication barrier significantly increased and more replication termination was observed at the barrier. Rrm3 also affects replication at the telomeres and internal tracts of C1-3A/TG1-3 telomeric DNA; in the absence of Rrm3 replication slowing at the repeats were increased and in addition replication stalling was observed at multiple sites within the sub-telomeric regions including in active origins (Ivessa, et al. 2002). At the silent mating-type regions and at the tRNA genes the Rrm3-dependent stalling was shown to be dependent on the presence of the associated protein complexes (Ivessa, et al. 2003). Also, loss of the ATPase function of Rrm3 has the same effect as deletion alleles, establishing that the catalytic activity of the helicase is needed for this function. Due to the increased genetic instability of Rrm3 mutants, their viability is dependent on mrc1, mre11, rad50, sgs1, srs2, top3, xrs2 and dia2, genes involved in activation of the inter-S phase checkpoint and replication fork restart (Torres, et al. 2004; Morohashi, et al. 2009). Interestingly, Dia2 is an F-box protein (E3 ubiquitin ligase) that also travels with the replication fork and might have a role at stalled DNA replication forks at protein-DNA barriers, perhaps by interaction with key substrates (Mimura, et al. 2009; Morohashi, et al. 2009). However, a recent study looking at the Fob1-dependent barrier using 2D-gel analysis of replication intermediates did not detect any effect on intensity of the barrier signal in a Δdia2 mutant (Bairwa, et al. 2011).
\n\t\tStalling of replication forks generally leads to the activation of the protein kinases of the PI(3) kinase-like kinase (PIKK) family, S. pombe Rad3, S. cerevisiae Mec1 and Mammalian ATR. One function of the activation of these kinases is to stabilize replication forks to prevent their collapse (Desany, et al. 1998; Lopes, et al. 2001). The PIKK mediated phosphorylation of a specialized histone called H2A.X (mammalian) or H2A (yeast) might help stabilize the stalled fork (Cobb, et al. 2005; Papamichos-Chronakis & Peterson, 2008) but also recruits DNA damage repair proteins (Mammalian Mdc1 and S. pombe Crb2 and Brc1; Du, et al. 2006; Williams, et al. 2010). Two studies have utilized this molecular beacon for identifying sites of replication stalling genome wide (Szilard, et al. 2010; Rozenzhak et al. 2010). In S. cerevisiae, γ-H2A (the phosphorylated form of H2A) enriched loci are concentrated at the rDNA locus, telomeres, DNA replication origins, LTRs, tRNA genes and centromeres, all of which are known replication barriers, but also at actively repressed protein-coding genes (Szilard, et al. 2010). In the latter case, the analysis showed that actively repressed genes, which are notably enriched for the transcription factors Sum1 and Ume6 that are known to recruit the two Hst1 and Rpd3 histone deacetylases (HDACs) (Kadosh & Struhl, 1997; Xie, et al. 1999; Robert, et al. 2004). This observation suggests that hetero-chromatin may pose an obstacle to progression of DNA replication forks. Importantly, loss of Hst1 or Rpd3 histone deacetylase activity abolished the γ-H2A enrichment at genes specifically regulated by Hst1 or Rpd3. Generally, γ-H2A enrichment was depended on both Mec1 and Tel1 (the latter is activated by double-stranded breaks), suggesting that both replication fork stalling as well as collapse occurred at the identified loci. Also, increased γ-H2A enrichment was observed in a Δrrm3 mutant background, suggesting a decreased ability of replication forks to pass through the barriers, thus leading to an increase in γ-H2A accumulation. A similar genome wide study in S. pombe identified γ-H2A enriched loci that corresponded well with those observed in S. cerevisiae, including the mating-type locus (including the RTS1 element, the region containing MPS1 and the imprint, and the IR elements that flank the transcriptionally silenced donor loci), the rDNA loci (including the gene coding region and the replication barriers), and all heterochromatin regions, including the centromeres (at the otr elements, but not the cnt or imr elements nor at the flanking inverted repeats) and telomeres, both Tf2-type retrotransposons and wtf elements and finally in a subset of gene coding sequences that were characterized by the presence of repetitive sequences (Szilard, et al. 2010). Contrary to what was observed in S. cerevisia γ-H2A accumulation was almost exclusively dependent on Rad3 and only at the telomere (in the absence of Rad3) on Tel1. In the mating-type region (the RTS1 element and MPS1), γ-H2A accumulation was dependent on Swi1 and Swi3 function in pausing and termination, while at the hetrochromatic regions γ-H2A accumulation is associated with the presence of Clr4-dependent heterochromatin and partially depends on Swi6. Several γ-H2A sites found in budding yeast were absent in fission yeast, including tRNA genes, LTRs (in the absence of the transposon) and replication origins. The absence of γ-H2A accumulation at tRNA genes and LTRs is interesting, as fork stalling is observed at these sites by 2D-gel analysis (see Section 5.), and might reflect that either different types of stalled fork exist or that the duration of the stall is important for γ-H2A accumulation.
\n\t\tIt is evident that many types of replication barriers have been defined. Whilst there are differences between these elements, there are also similarities. At some barriers replication forks only pause and then restart again without fork collapse. However, at others the replication fork is stalled until an approaching fork arrives from the other side for mediation of replication termination. Different molecular responses and levels of genetic instability are observed at the barriers. What determines the fate of a stalled replication fork at a barrier is still generally unknown. However, it is evident that helicases, such as S. cerevisiae Rrm3 and S. pombe Srs2 promote replication through protein mediated barriers (Section 8. & 10.) and Tof1 and Mrc1 through barrier caused by “structure” in the template (Section 6.), while S. pombe Rtf2 acts to stabilize the stalled fork for replication termination (Section 8.). It is also evident, that many different proteins can act as replication impediments. Generally, these proteins do not promote barrier activity through the formation of “stable” complexes, although in the absence of S. cerevisiae Rrm3 barrier activity stalling at stable protein-DNA complexes can be observed (Section 9.). Barrier activity is most likely generated via direct interaction(s) with the progressing replisome. For example, most protein-mediated barriers are polar, only stalling replication forks when encountered from one side, while for S. pombe Sap1 acts as a barrier at some cis-acting sites but not others (Sections 8. & 3.6). It should be mentioned that strong replication barriers often consist of several closely spaced cis-acting sequences where one or more trans-acting factors mediate the replication barrier. Also, these trans-acting factors have the ability to dimerize or polymerize, potentially increasing the efficiency of interaction, but more likely providing additional topological constraints when the DNA is unwound by the replicative helicase. Also, it is common for known protein-mediated barrier activity to depend on the trans-acting factors Tof1/Csm3 (S. cereviaise) and Swi1/Swi3 (S. pombe), although there are some notable exceptions (for example, see Pryce et al. 2009). Putatively, the S. cerevisiae Tof1/Csm3 or S. pombe Swi1/Swi3 heteromeric complexes slide along the double-stranded DNA in front of the replicative helicase and senses the presence of barrier proteins. It has been shown earlier that in the absence of S. cerevisiae Tof1/Csm3 an uncoupling of the replicative helicase from the replicative polymerases can occur (Katou, et al. 2003; Nedelcheva, et al. 2005), thus Tof1/Csm3 (and phylogenetic related proteins) could directly inhibit MCM function when barrier proteins are encountered. Consistent with this model, the 3’ end of the leading-stand and the 5’ end of the lagging-strand have been mapped in close proximity about approximately 30-40 bp from the cis-acting sequences that mediate the barrier activity both at the S. cerevisiae rDNA barrier and at the S. pombe\n\t\t\t\tMPS1 site (Figure 5A; Sections 3.6 & 8.1).
\n\t\t\tInterestingly, DNA structures in the template can also stall replication fork progression in a site-specific manner. These barrier signals most likely act on the lagging-strand as impediments to polymerase progression (Figure 5B). Interestingly, here S. cerevisiae Tof1 and Mrc1 are required for efficient replication through the elements (Mrc1 does not affect barrier activity at protein barriers), but not through the checkpoint activation function of these proteins. Still, the characteristics of these barriers suggest that the mechanism by which this
\n\t\t\tThe two types of replication barriers described. A) DNA bound factors can stall replisome progression, leading to a 3’ leading-strand end and 5’ lagging-strand end a certain distance from the barrier. B) Structure at the lagging-strand template leads to stalling of replisome progression.
type of barriers stalls replication forks is different from the one by which protein barriers act. Potentially, structures in the lagging-strand template strand could also explain by S. pombe tRNA genes mediate barrier activity in a Swi1 independent manner.
\n\t\t\tIt is also evident from this comparison that replication barriers both prevent and cause genetic instability and a number of key points highlight this:
\n\t\t\tMany of the described barriers have either been shown or are thought to prevent conflicts between progressing RNA polymerases I, II and III and replication forks, thus promoting genetic stability.
Other barriers are thought to promote telomere addition for maintenance of genetic stability.
Several barriers have been shown to cause genetic instability, including rDNA barriers (see Section 2.4), the RTS1 element (Ahn, et al. 2005), transposons (Zaratiegui, et al. 2011), as well as DNA structure in the template (Section 7.).
Again others have specific roles in induction of recombination events, including genetic rearrangements important for contraction/expansions of rDNA arrays and cellular differentiation or development in S. pombe and Tetrahymena (Sections 3.2 & 8.).
It is highly likely that additional biological roles will be defined for replication barriers in the future. Here, research into such genetic elements’ roles in cellular differentiation and development in higher eukaryotes would be important. In addition, it will be interesting to understand how replication barriers drive evolution through instability at the stalled forks. It is already evident from studies of fragile sites, genomic rearrangements, repeat expansion/contraction and mutations that underlie the genetic instability of cancer cells, that replication barriers are likely to have a profound role in disease formation. Thus, the importance of a better understanding of the molecular processes that lead to stalling of replication forks and that control the events at these forks, should not be underestimated.
\n\t\tThe desire to limit the adverse external effects associated with the development of motorization and transport, mainly based on the reciprocating internal combustion engine as the primary power source, reveals primarily with limitation the allowable level of emissions of harmful substances in the exhaust gases, that is, carbon monoxide, CO; hydrocarbons, HC; nitrogen oxides, NOx; and particulate matter, PM. Moreover, in the perspective of growing global warming phenomenon and dropping resources of liquid fuels, particular attention is paid to the reduction of fuel consumption and thus CO2 emission. Unfortunately, the physical and chemical rules of working processes in piston engines do not allow to meet all the above requirements in a simple manner. Despite significant progress made in recent years, further improvement of the ecological and energetic parameters of reciprocating engines requires further changes in their design, covering practically all functional systems.
\nOne of the more effective paths, although at the current stage of development is still having many technical and operational difficulties, is the construction of engines in which the compression ratio becomes a regulation parameter and can be changed continuously in a wide range and relatively short time. In a conventional engine, the compression ratio—the ratio of the smallest to the largest cylinder volume at piston top dead center positions—is constant and determined by the geometry of the cylinder and crank mechanism. The new technology called variable compression ratio, and marked with the VCR symbol, completely changes the previously unchanged feature of the engines. Many companies have noticed significant potential hidden in variable compression systems and focused their entire attention on finding ways to apply and use this feature. Therefore, over the last years, there has been a growing interest in this type of innovative construction.
\nThe origination of the idea of variable compression ratio was the desire to use for the engine supplying fuels with different properties; it is the so-called flex-fuel capability. Although it is still a valuable property, currently in the development of internal combustion engines, a special emphasis is placed on reducing fuel consumption, and thus CO2 emissions, as well on reducing the emission of harmful exhaust components—carbon monoxide, hydrocarbons, nitrogen oxides, or particulates.
\nGlobal automotive industry as well science and research institutions involved in the development of VCR technology say about the potential for reducing fuel consumption by using a variable compression ratio in engines of different capacity. Significant economic benefits are particularly visible when variable compression ratio technology is used for high-power engines. It is significant also if these are naturally aspirated or boosted engines with direct injection (DFI) and variable-controlled valve actuation (VVA). Figure 1 illustrates the potential benefits for the individual and combined use of these solutions.
\nThe predicted increase in engine fuel economy with using VCR technology [1].
Significantly, greater benefits in the field of fuel economy and engine ecology can be obtained by combining the VCR and VVA variable valve actuation systems (Figure 2). The use of these systems allows, for example, the implementation of the Atkinson working cycle and the using engines of smaller dimensions with maintained high operational parameters, that is, according to the idea of “ultra-downsizing.”
\nThe foreseen decrease of CO2 emissions, thanks to the use of VCR and VVA technologies [1].
“Downsizing” is a relatively new development trend of piston engines, which gives a response to strong pressure on reducing fuel consumption and improving the overall engine efficiency. The idea of downsizing is to reduce the cubic capacity of the powerdrives and increase the power ratio, mainly by using still higher and higher boosting pressure. Reduced stroke volume can be also obtained, among others, by reducing the number of cylinders. It means the mechanical and thermal losses are reduced, as well cylinder charge exchange losses, the so-called “pumping” losses too. At the same, the overall efficiency of the engine increases. On the other hand, an increase in the boost pressure requires a reduction of geometric compression ratio to avoid adverse phenomena in the combustion process. Due to the direct relationship with the cycle efficiency, it is preferred to use as high compression ratio as possible. So, the compression ratio value must be a compromise between achieving the high thermal efficiency of the cycle and other restrictions, such as: knock limit, level of mechanical and/or thermal loads, maximum rate of pressure rising (engine run hardness), etc. However, these limitations are only in force at high engine loads, especially at high boosting. In conventional engines, the compression ratio is optimized and finally determined for these operating conditions. However, this is not a significant area of their usual operation. At low and moderate loads, the compression ratio could be much higher, giving increased operational efficiency of the vehicle. Therefore, the VCR technology enables a significant extension of the “downsizing” range, allowing further reduction of the displacement volume and the use of even higher boosting pressures. It is estimated that this method of adjusting the working parameters of the spark-ignition engine can result in a reduction in the fuel consumption by up to 30% without a significant increase of toxic exhaust compound emission [1].
\nFinally, the next area of using VCR technology is the possibility of effective implementation of advanced, low-temperature LTC combustion processes (low-temperature combustion). They are characterized by extremely low emission levels of toxic compounds as a result of high complementarity of the combustion phase, but conducted under conditions with reduced charge temperature. Especially, a lack of temperature gradients in the combustion chamber is the main cause of avoiding nitrogen oxides’ formation. There are, however, certain difficulties in obtaining low-temperature combustion stability under the high engine loads. Within this range of engine operation, a new VCR variable compression ratio technology exhibits a promising application potential, thanks to the high ability in moderating the thermodynamic conditions in the combustion chamber, which determine the initiation and course of combustion process.
\nTheoretically, there are several possible methods of using the variable compression ratio VCR technology in piston engines. Some of them were used in prototype engines and they undergo operational tests.
\n\nTable 1 schematically presents selected VCR layouts together with a brief analysis of their technical and operational features, including advantages or disadvantages in relation to the conventional construction of the engines. Noteworthy is the solution (f) of a complex lever-gear crank system, developed and applied by the French research group MCE-5 Development [2], as well as the SAAB SVC engine [3, 4], according the principle (a) and solution (c) implemented in the FEV Motorentechnik research engine [5].
\nTechnical methods of application VCR technology in piston engines and their technical and operational features.
↗—improvement, ↘—deterioration, ↑—high mark, ↓—low mark, and ≠—distinctive mark.
There are many specific and unique constructions of VCR engines or even engine ideas and patents. Table 1 collects the best-known approaches for VCR engine:
articulated monohead—the SAAB completely functional engine SVC [3, 4],
piston of variable deck height—different layouts presented by Daimler-Benz and Ford, as well [6],
eccentrics on crankshaft bearings developed by FEV [5],
multilink rod-crank mechanisms developed by Nissan [7],
secondary moving piston or valve in cylinder head—different Ford and Volvo/Alvar proposals [6],
precisely shifted cylinder block—cylinder head assembly—used in authors’ own project [8, 9].
Each of above are presented and widely discussed by Shaik et al. [6]. The SAAB’s SVC engine according to the solution (a) has been developed earlier by Larsen [3]. The compression ratio is variable from 8:1 to 14:1. Similarly to the shifted cylinder head method (g), it reveals good compression ratio control ability, but with slight change in piston kinematics. As a common drawback of both systems, a worse reliability and durability characteristic can be pointed. The solution (b) based on piston deck height variation uses a complicated special piston construction [6]. It also does not provide easy and precise control of compression ratio. Eccentric on main bearings (c) seems to be devoid of substantial disadvantages, but it makes the crankshaft block more complex. This solution is developed by FEV and used in their concept VCR car [5]. Nissan Motors developed a multilink rod-crank mechanism [6] according to the layout (d). It provides moderate compression ratio control ability at significant change in piston kinematics. Changing compression ratio using a small chamber with moving piston/valve (e) is relatively simple method to be applied in standard engines conversion into the VCR engines. As the drawback of this manner for changing compression ratio, the poor combustion chamber integrity can be pointed [6]. The gear-based crank mechanism (f) is very advanced technique extensively developed by MCE-5 research group [1, 2]. It shows high precision in CR control and profitable changes in piston kinematics that avoids side forces acting on the piston.
\nAnalyzing the possible solutions of VCR engines, both hypothetical constructions and actual prototype units, two general strategies for changing the value of the compression ratio during the engine run can be noticed.
The change and control of the compression ratio at the assumed level takes place by changing the position or geometry of the engine part, which consist of the cylinder head assembly. This method does not interfere with the moving parts of the crank-piston system, thus the friction losses and kinematics of the crank-piston system during engine operation remain unchanged or change in a very small extent comparing to a conventional engine.
The change of the compression ratio is a result of the intended changes in the geometry and/or kinematics of the crank-piston system due to special constructions of mechanisms allowing for the correction of the distance between the top plane of the piston and the bottom plane of the head. In this case the power of friction losses in the crank-piston system usually increases, although it is also possible to be reduced (e.g., solution (f)—Table 1). Sometimes variation of the compression ratio according to these concepts also causes an unfavorable change in the cylinder stroke volume (e.g., solution (d)—Table 1).
Despite the fact that the idea of variable-pressure VCR engines is associated with significant construction and technological complexity and many operational problems, it is estimated that it starts to become a technical standard for automotive piston engines in the near future (see Figure 3).
\nForecasts for the development and share of selected advanced technologies in the combustion powerdrives of motor vehicles [10].
Therefore, it was accepted that development and building a prototype variable compression ratio engine, along with the acquired knowledge and experience, will allow for successive improvement of the design and, as a result, get a fully functional, unique research instrument that makes possible to perform a number of innovative scientific works.
\nOn the basis of the analyses in the field of variable compression ratio technology, taking into account all advantages and disadvantages of the known technologies for of variable compression ratio engines and existing prototypes as well as own manufacturing capabilities, it was decided that the construction of the test engine will be carried out according to for the kinematic system shown on case (g) in Table 1, that is, consisting of controlled positioning and movement of the cylinder head assembly along the cylinder axis. This solution is characterized by relatively low implementation costs due to the possibility of conversion of a standard piston engine into the VCR one, simplicity of construction and control, while ensuring a relatively wide range of changes of compression ratio at a high accuracy in positioning. The engine will be based on a serial produced combustion engine. It was assumed that for the purposes of the assumed scope of experimental tests, it will be necessary to obtain a wide range of compression ratio variation covering typical values for both spark and diesel engines, that is, from around 9:1 up to 19:1. The test engine should be also liquid cooled to ensure good temperature stability during research.
\nA medium-speed, liquid-cooled 4-cylinder diesel engine manufactured by VEB IFA-Motorenwerk Nordhausen type 4 VD 14.5/12-1 SRW was selected for the construction of the VCR engine. The unique structural feature of this engine, which decided on its selection, was the physically existing plane that divides the crankcase from the cylinder assembly (see Figure 4).
\nThe main cross sections of the 4 VD 14.5/12-1 SRW engine as the basis for the own designed research unit in the VCR technology with the dividing planes of the engine body shown [11].
The basic parameters of the 4 VD engine are as follows: cylinder diameter—120 mm, piston stroke—145 mm, displacement—6560 ccm, original geometric compression ratio—18:1, valve drive system: OHV overhead valves with camshaft located in the crankshaft block, cam followers, sticks, valve arms mounted on the axle above the head. Detailed engine specifications are described in Table 2.
\nProducer | \nVEB IFA-Motorenwerk Nordhausen | \n
---|---|
Type | \n4-stroke, diesel | \n
Number of cylinders | \n4 | \n
Ignition order | \n1-3-4-2 | \n
Cylinder layout | \nIn-line | \n
Piston stroke | \n145 mm | \n
Cylinder diameter | \n120 mm | \n
Displacement | \n6560 ccm | \n
Compression ratio | \n18:1 | \n
Rated power | \n92 kW (125 KM) | \n
Cranckshaft speed at rated power | \n2300 rpm | \n
Maximum torque | \n430 Nm | \n
Cranckshaft speed at max. torque | \n1350 rpm | \n
Mean effective pressure | \n0.77 MPa | \n
Specific fuel consumption for rated power | \n240 g/kW·h (175 g/KM·h) | \n
Minimum specific fuel consumption | \n218 g/kW·h (160 g/KM·h) | \n
Lubrication system | \nClosed circulation, pressurized | \n
Fuel delivery | \nDirect injection (system MAN), single-hole sprayer, in-line section fuel pump with mechanical regulation of engine speed | \n
Initial pressure of injector opening | \n17.5 MPa | \n
Engine starter | \nElectric motor | \n
Power and supply voltage of engine starter | \n3 kW, 24 V | \n
Original technical specification of the 4 VD 14.5/12-1 SRW engine [11].
Geometric dimensions of the 4 VD 14.5/12-1 SRW engine allowed to determine how the compression ratio will change with the cylinder head assembly moving along the cylinder axis according to the relationship (Eq. (1)):
\nwhere ε´ is compression ratio as a function of the cylinder head assembly shift, ε is original compression ratio, Vc is cylinder displacement, D is cylinder diameter, h is shift value of cylinder head assembly relative to the initial position.
\n\nEq. (1), substituted with appropriate values, shows that the range of the cylinder head assembly tilting from initial position up to 10 mm travel gives the compression ratio changes from 19:1 to 9:1, according to the curve shown in the Figure 5. The range of these changes essentially coincides with the desired research scope of the engine. If necessary, it can be changed relatively easily by replacing the pistons with different volume of the combustion chamber [8, 9].
\nCompression ratio versus cylinder shift value for 4 VD 14.5/12-1 SRW engine.
The adopted concept of changing the compression ratio requires the use of an accurate, precise cylinder head assembly shifting mechanism in relation to the crankshaft block. The requirement of this mechanism, in addition to the high accuracy of positioning and rapid change of the position of the cylinders, is to transfer gaseous forces generated by the combustion process in individual engine cylinders. The value of these forces can be determined from Eq. (2):
\nwhere Fmax is the maximum force acting on the shifting system due to the gas pressure in the cylinder, pmax is maximum gas pressure in the cylinder, and D is cylinder diameter.
\nAssuming the maximum gas pressure in cylinders at 10 MPa, we obtain the force generated by a single cylinder at the level of 113 kN. Hence, the sliding mechanism must have adequate strength, but also rigidity, operational reliability, small dimensions and relatively high positioning resolution, especially in the range of high values of compression ratio.
\nThe task of the newly designed mechanism for compression ratio changing is precise shifting the 4-cylinder “cylinder head” assembly in the range of 0–10 mm by means of synchronously rotating two eccentric shafts that are connected to the sliding elements by kind of yokes—connecting rods. The layout diagram and the source of the main mechanical loads are shown in Figure 6. The analysis of forces and torques shows that the eccentric shafts will be loaded with a twisting torque Ms of approx. 300 Nm each.
\nDiagram of the yoke-eccentric cylinder sliding mechanism and the main sources of mechanical loads.
\nFigure 7 shows the location of eccentric shafts together with the shaft drive system. Both shafts have bearings on both ends and in the middle of their length. At the free ends of both shafts there are two geared right-angle power transmissions; their inputs are connected by a common drive shaft that is driven by a synchronous servomotor with a mechanical brake. The wheelbase of the shafts is approx. 380 mm, which directly fits to the design features of the test engine.
\nProject of the location of eccentric shafts with the drive system diagram.
Analysis of loads shows that each of the bevel-geared transmissions has to transfer a maximum torque less than 300 Nm, while the main servomotor has to generate a double value of that torque, that is, at least 600 Nm.
\nTherefore, an appropriate selection of working elements has been made, taking into account the structural safety factors. The bevel gearboxes TRAMEC in the version RA 38AC 1:1 E B3 with the rated torque Ma = 320 Nm are used as the right-angle drives. As the servomotor a two-stage flat reducer, type Stöber SMS version F402AGN0470 EZ503U EL1, with an acceleration torque of 700 Nm, driven by the Stöber POSIDRIVE MDS5110A/L 11.0 kW 3 × 400 V inverter is used (Figure 8). All gear units are with reduced mid-gear lash to the value below 10 arc minutes.
\nOverall views of the RA type TRAMEC bevel gearbox, Stöber SMS servomotor, and Stöber POSIDRIVE MDS inverter.
Construction work began with the reverse engineering process on the research engine, that is, scanning the spatial engine body with the determination of characteristic points, surfaces, distances, clearances, etc., allowing the design and manufacture of other engine components and subassemblies. As previously mentioned, the characteristic feature of IFA 4 VD 14.5/12-1 SRW engine, which influenced the decision on its selection for adaptation works is the fact that the engine block is not permanently fixed to the cylinders. The division plane is shown in Figure 9. Its physical presence gave the opportunity to design and build an appropriate drive mechanism to realize the movement of the cylinders (together with the heads) in the vertical direction.
\n3D scanning image of the IFA 4 VD engine as a base for performing necessary design and technological changes; the green plane is marked showing the division plane between the crankcase block and the cylinder blocks.
The basic elements of the cylinder sliding system are the servomotors chosen with catalogs, two bevel gears, drive couplings, and two eccentric shafts, connecting rods and a designed and made main support plate that keeps the cylinders. The main board (Figure 10, dark blue color) is seated and attached to the cylinder blocks using special threaded mounting bolts.
\nDesign of the cylinder support plate and its mounting on the screws fitted into the cylinder blocks.
To allow the additional space for insertion of a flexible seal gasket between crankshaft block and cylinder blocks it was necessary to change the pistons with the larger height ones by at least 5 mm. Suitable pistons that meet the necessary dimensions for the designed VCR engine were adopted from the HANOMAG D942 engines.
\nThe next key stage in the VCR engine design process was the exact machining of eccentric shafts for the cylinder sliding system together with a set of eight connecting yokes. To ensure proper dimensional accuracy, technological work was carried out on CNC machine tools. Figure 11 shows the connecting yokes fastened with the eccentric shafts.
\nConnecting yokes mounted with the eccentric shafts.
The movement of the supporting plate together with the cylinders is enforced by an eccentric-crank mechanism driven by a complex servomechanism (Figure 12), that is, through two angle bevel gears and two eccentric shafts. The elements shown in orange make the assembly fixing the axle passing through the connecting rod holes. Eccentric shafts are mounted in sleeves welded to the transverse beams (green and yellow). The drive for eccentric shafts is transmitted via two ROTEX GS clutches. Any disorders and risk of misalignments in movement of the cylinder-cylinder head assembly is secured by set of sliding barrels. Sliding barrels are permanently fixed in the crankcase and fitted into the precise holes made in the cylinders body.
\nView of the assembly of the cylinder blocks sliding system.
The entire design of the VCR engine, for a better illustration of its structure complexity, is presented in isometric views in Figure 13, while the finally completed research engine with variable compression ratio is presented in Figure 14.
\nAn isometric view of the VCR engine with assembled with the cylinder sliding system and the drive mechanism of eccentric shafts.
View of the complete VCR engine during functional tests.
Piston engine for many decades is a basic and commonly used source of mechanical drives in various types of machinery and technical equipment, including motor vehicles and other means of transportation. Despite the various controversial forecasts and views that have recently appeared, and not always are based on trusted and documented technical knowledge, the combustion engine will certainly remain an irreplaceable source of propulsion for many branches of transport and industry. One should keep in mind the intense scientific, technical, and technological progress that makes the final product even more and more technically perfect. Taking into account the current development trends that arisen from an experience of recent years, which are focused mainly on improving combustion processes, it can be noted that the presented technical development of VCR internal combustion engines gives a significant contribution in this process.
\nA great innovation and application potential is shown by the worked out original design, constructional and technological achievements covering a four-cylinder combustion engine with a variable compression ratio VCR feature. Attempts to develop such an original powerdrive unit, except for some major automotive industry efforts, were usually finished unsuccessfully. The developed design of the VCR engine opens up new research and development opportunities that were not available before. It concerns mainly to new directions of improvement of engine working processes and exploitation possibilities of internal combustion engines, that is, research on advanced, low-temperature combustion processes or research on the unification and flexible use of various fuels for transportation, including alternative fuels of different reactivities.
\nAuthors wish to thank to the Ministry for Science and Higher Education in the Republic of Poland for their financial support of this work.
\nIf you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links.
",metaTitle:"List of Institutions by Country",metaDescription:"If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. However, if your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).",metaKeywords:null,canonicalURL:"open-access-funding-institutions-list",contentRaw:'[{"type":"htmlEditorComponent","content":"Book Chapters and Monographs
\\n\\nBook Chapters
\\n\\nMonographs Only
\\n\\n\\n\\nBook Chapters and Monographs
\\n\\nMonographs Only
\\n\\nBook Chapters and Monographs
\\n\\n\\n\\nBook Chapters and Monographs
\\n\\n\\n\\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\\n\\nCSIC affiliated authors can also take advantage of a central Open Access fund (amounting to 10,000 EUR) to cover up to 50% of the rest of the OAPF until it expires. Effective for chapters accepted from January 1, 2020.
\\n\\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\\n\\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\\n\\n\\n\\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\\n\\nBook Chapters and Monographs
\\n\\nBook Chapters and Monographs
\\n\\nBook Chapters and Monographs
\\n\\nBook Chapters and Monographs
\\n\\nThe Claremont Colleges are pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\\n\\nCorresponding authors will receive a 15% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\\n\\nThe University of Massachusetts, Amherst is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\\n\\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\\n\\nThe University of Surrey is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\\n\\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\\n\\nMonographs Only
\\n\\n\\n\\nImportant: You must be a member or grantee of the above listed institutions in order to apply for their Open Access publication funds.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Book Chapters and Monographs
\n\n\n\nBook Chapters
\n\nMonographs Only
\n\n\n\nBook Chapters and Monographs
\n\nMonographs Only
\n\nBook Chapters and Monographs
\n\n\n\nBook Chapters and Monographs
\n\n\n\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\n\nCSIC affiliated authors can also take advantage of a central Open Access fund (amounting to 10,000 EUR) to cover up to 50% of the rest of the OAPF until it expires. Effective for chapters accepted from January 1, 2020.
\n\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\n\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\n\n\n\nCorresponding authors will receive a 25% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters. A 20% discount for publishing a long-form monographs, 25% for compacts and 23% for short-form monographs.
\n\nBook Chapters and Monographs
\n\nBook Chapters and Monographs
\n\nBook Chapters and Monographs
\n\n\n\nBook Chapters and Monographs
\n\nThe Claremont Colleges are pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\n\nCorresponding authors will receive a 15% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\n\nThe University of Massachusetts, Amherst is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\n\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\n\nThe University of Surrey is pledging funds via the Knowledge Unlatched program to ensure academics can publish Open Access content more easily.
\n\nCorresponding authors will receive a 10% discount on their Open Access Publication Fees (OAPF) for Open Access book chapters or monograph publications. To use the discount you will need to verify your institutional email address. These discounts are valid from 2020 to 2022.
\n\nMonographs Only
\n\n\n\nImportant: You must be a member or grantee of the above listed institutions in order to apply for their Open Access publication funds.
\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:5766},{group:"region",caption:"Middle and South America",value:2,count:5227},{group:"region",caption:"Africa",value:3,count:1717},{group:"region",caption:"Asia",value:4,count:10366},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15789}],offset:12,limit:12,total:118187},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"23"},books:[{type:"book",id:"10656",title:"Intellectual Property",subtitle:null,isOpenForSubmission:!0,hash:"135df9b403b125a6458eba971faab3f6",slug:null,bookSignature:"Dr. Sakthivel Lakshmana Prabu and Dr. Suriyaprakash TNK",coverURL:"https://cdn.intechopen.com/books/images_new/10656.jpg",editedByType:null,editors:[{id:"91590",title:"Dr.",name:"Sakthivel",surname:"Lakshmana Prabu",slug:"sakthivel-lakshmana-prabu",fullName:"Sakthivel Lakshmana Prabu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10658",title:"Multilingualism",subtitle:null,isOpenForSubmission:!0,hash:"a6bf171e05831c00f8687891ab1b10b5",slug:null,bookSignature:"Prof. Xiaoming Jiang",coverURL:"https://cdn.intechopen.com/books/images_new/10658.jpg",editedByType:null,editors:[{id:"189844",title:"Prof.",name:"Xiaoming",surname:"Jiang",slug:"xiaoming-jiang",fullName:"Xiaoming Jiang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10662",title:"Pedagogy",subtitle:null,isOpenForSubmission:!0,hash:"c858e1c6fb878d3b895acbacec624576",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10662.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10913",title:"Indigenous Populations",subtitle:null,isOpenForSubmission:!0,hash:"c5e8cd4e3ec004d0479494ca190db4cb",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10913.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10914",title:"Racism",subtitle:null,isOpenForSubmission:!0,hash:"0737383fcc202641f59e4a5df02eb509",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10914.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:14},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:3},{group:"topic",caption:"Business, Management and Economics",value:7,count:1},{group:"topic",caption:"Chemistry",value:8,count:6},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:5},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:24},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:2},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Social Sciences",value:23,count:2},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:12,limit:12,total:5},popularBooks:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9043",title:"Parenting",subtitle:"Studies by an Ecocultural and Transactional Perspective",isOpenForSubmission:!1,hash:"6d21066c7438e459e4c6fb13217a5c8c",slug:"parenting-studies-by-an-ecocultural-and-transactional-perspective",bookSignature:"Loredana Benedetto and Massimo Ingrassia",coverURL:"https://cdn.intechopen.com/books/images_new/9043.jpg",editors:[{id:"193200",title:"Prof.",name:"Loredana",middleName:null,surname:"Benedetto",slug:"loredana-benedetto",fullName:"Loredana Benedetto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5227},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8098",title:"Resources of Water",subtitle:null,isOpenForSubmission:!1,hash:"d251652996624d932ef7b8ed62cf7cfc",slug:"resources-of-water",bookSignature:"Prathna Thanjavur Chandrasekaran, Muhammad Salik Javaid, Aftab Sadiq",coverURL:"https://cdn.intechopen.com/books/images_new/8098.jpg",editedByType:"Edited by",editors:[{id:"167917",title:"Dr.",name:"Prathna",middleName:null,surname:"Thanjavur Chandrasekaran",slug:"prathna-thanjavur-chandrasekaran",fullName:"Prathna Thanjavur Chandrasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editedByType:"Edited by",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8415",title:"Extremophilic Microbes and Metabolites",subtitle:"Diversity, Bioprospecting and Biotechnological Applications",isOpenForSubmission:!1,hash:"93e0321bc93b89ff73730157738f8f97",slug:"extremophilic-microbes-and-metabolites-diversity-bioprospecting-and-biotechnological-applications",bookSignature:"Afef Najjari, Ameur Cherif, Haïtham Sghaier and Hadda Imene Ouzari",coverURL:"https://cdn.intechopen.com/books/images_new/8415.jpg",editedByType:"Edited by",editors:[{id:"196823",title:"Dr.",name:"Afef",middleName:null,surname:"Najjari",slug:"afef-najjari",fullName:"Afef Najjari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"158",title:"Metals and Nonmetals",slug:"metals-and-nonmetals",parent:{title:"Materials Science",slug:"materials-science"},numberOfBooks:113,numberOfAuthorsAndEditors:2715,numberOfWosCitations:2995,numberOfCrossrefCitations:2014,numberOfDimensionsCitations:4557,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"metals-and-nonmetals",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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",editedByType:"Edited by",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",authoredCaption:"Edited by"}},{type:"book",id:"8787",title:"Bismuth",subtitle:"Fundamentals and Optoelectronic Applications",isOpenForSubmission:!1,hash:"7751170d0b538f61d14a27a56e6567a5",slug:"bismuth-fundamentals-and-optoelectronic-applications",bookSignature:"Yanhua Luo, Jianxiang Wen and Jianzhong Zhang",coverURL:"https://cdn.intechopen.com/books/images_new/8787.jpg",editedByType:"Edited by",editors:[{id:"226148",title:"Dr.",name:"Yanhua",middleName:null,surname:"Luo",slug:"yanhua-luo",fullName:"Yanhua Luo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9949",title:"Lead Chemistry",subtitle:null,isOpenForSubmission:!1,hash:"b2f999b9583c748f957f612227976570",slug:"lead-chemistry",bookSignature:"Pipat Chooto",coverURL:"https://cdn.intechopen.com/books/images_new/9949.jpg",editedByType:"Edited by",editors:[{id:"197984",title:"Ph.D.",name:"Pipat",middleName:null,surname:"Chooto",slug:"pipat-chooto",fullName:"Pipat Chooto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9190",title:"Stability and Applications of Coordination Compounds",subtitle:null,isOpenForSubmission:!1,hash:"3f07c532e478beb8fcd2fe53b8c9bcfd",slug:"stability-and-applications-of-coordination-compounds",bookSignature:"Abhay Nanda Srivastva",coverURL:"https://cdn.intechopen.com/books/images_new/9190.jpg",editedByType:"Edited by",editors:[{id:"293623",title:"Dr.",name:"Abhay Nanda",middleName:"Nanda",surname:"Srivastva",slug:"abhay-nanda-srivastva",fullName:"Abhay Nanda Srivastva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7787",title:"Rare Earth Elements and Their Minerals",subtitle:null,isOpenForSubmission:!1,hash:"7ba4060b0830f7a68f00557da8ed8a39",slug:"rare-earth-elements-and-their-minerals",bookSignature:"Michael Aide and Takahito Nakajima",coverURL:"https://cdn.intechopen.com/books/images_new/7787.jpg",editedByType:"Edited by",editors:[{id:"185895",title:"Dr.",name:"Michael",middleName:"Thomas",surname:"Aide",slug:"michael-aide",fullName:"Michael Aide"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7722",title:"Recent Advancements in the Metallurgical Engineering and Electrodeposition",subtitle:null,isOpenForSubmission:!1,hash:"0d7ff67bd6f4c13830658bc6f9a75851",slug:"recent-advancements-in-the-metallurgical-engineering-and-electrodeposition",bookSignature:"Uday Basheer Al-Naib, Dhanasekaran Vikraman and K. Karuppasamy",coverURL:"https://cdn.intechopen.com/books/images_new/7722.jpg",editedByType:"Edited by",editors:[{id:"182041",title:null,name:"Uday",middleName:"M.",surname:"Basheer Al-Naib",slug:"uday-basheer-al-naib",fullName:"Uday Basheer Al-Naib"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7775",title:"Metallic Glasses",subtitle:null,isOpenForSubmission:!1,hash:"665fb007e1e410d119fc09d709c41cc3",slug:"metallic-glasses",bookSignature:"Dragica Minić and Milica Vasić",coverURL:"https://cdn.intechopen.com/books/images_new/7775.jpg",editedByType:"Edited by",editors:[{id:"30470",title:"Prof.",name:"Dragica",middleName:"M",surname:"Minić",slug:"dragica-minic",fullName:"Dragica Minić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8653",title:"Electromagnetic Materials and Devices",subtitle:null,isOpenForSubmission:!1,hash:"0cc0489a203ae888b1105719a4e70ecd",slug:"electromagnetic-materials-and-devices",bookSignature:"Man-Gui Han",coverURL:"https://cdn.intechopen.com/books/images_new/8653.jpg",editedByType:"Edited by",editors:[{id:"250649",title:"Prof.",name:"Man-Gui",middleName:null,surname:"Han",slug:"man-gui-han",fullName:"Man-Gui Han"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8886",title:"Cobalt Compounds and Applications",subtitle:null,isOpenForSubmission:!1,hash:"0241f740fc6e17cd9dc69362ef388d04",slug:"cobalt-compounds-and-applications",bookSignature:"Yasemin Yıldız and Aynur Manzak",coverURL:"https://cdn.intechopen.com/books/images_new/8886.jpg",editedByType:"Edited by",editors:[{id:"208129",title:"Dr.",name:"Yasemin",middleName:null,surname:"Yıldız",slug:"yasemin-yildiz",fullName:"Yasemin Yıldız"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8416",title:"Non-Equilibrium Particle Dynamics",subtitle:null,isOpenForSubmission:!1,hash:"2c3add7639dcd1cb442cb4313ea64e3a",slug:"non-equilibrium-particle-dynamics",bookSignature:"Albert S. Kim",coverURL:"https://cdn.intechopen.com/books/images_new/8416.jpg",editedByType:"Edited by",editors:[{id:"21045",title:"Prof.",name:"Albert S.",middleName:null,surname:"Kim",slug:"albert-s.-kim",fullName:"Albert S. Kim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8408",title:"Titanium Alloys",subtitle:"Novel Aspects of Their Manufacturing and Processing",isOpenForSubmission:!1,hash:"e5533136b732dc4ada818553023d4d55",slug:"titanium-alloys-novel-aspects-of-their-manufacturing-and-processing",bookSignature:"Maciej Motyka, Waldemar Ziaja and Jan Sieniawsk",coverURL:"https://cdn.intechopen.com/books/images_new/8408.jpg",editedByType:"Edited by",editors:[{id:"101690",title:"Associate Prof.",name:"Maciej",middleName:null,surname:"Motyka",slug:"maciej-motyka",fullName:"Maciej Motyka"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:113,mostCitedChapters:[{id:"37067",doi:"10.5772/35482",title:"Fourier Transform Infrared Spectroscopy for Natural Fibres",slug:"fourier-transform-infrared-spectroscopy-for-natural-fibres",totalDownloads:8290,totalCrossrefCites:119,totalDimensionsCites:285,book:{slug:"fourier-transform-materials-analysis",title:"Fourier Transform",fullTitle:"Fourier Transform - Materials Analysis"},signatures:"Mizi Fan, Dasong Dai and Biao Huang",authors:[{id:"104647",title:"Prof.",name:"Mizi",middleName:null,surname:"Fan",slug:"mizi-fan",fullName:"Mizi Fan"}]},{id:"60680",doi:"10.5772/intechopen.76082",title:"Environmental Contamination by Heavy Metals",slug:"environmental-contamination-by-heavy-metals",totalDownloads:12266,totalCrossrefCites:65,totalDimensionsCites:115,book:{slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. Muedi",authors:[{id:"225304",title:"Dr.",name:"Vhahangwele",middleName:null,surname:"Masindi",slug:"vhahangwele-masindi",fullName:"Vhahangwele Masindi"},{id:"241403",title:"M.Sc.",name:"Khathutshelo",middleName:"Lilith",surname:"Muedi",slug:"khathutshelo-muedi",fullName:"Khathutshelo Muedi"}]},{id:"46243",doi:"10.5772/57255",title:"Corrosion Inhibitors – Principles, Mechanisms and Applications",slug:"corrosion-inhibitors-principles-mechanisms-and-applications",totalDownloads:13e3,totalCrossrefCites:30,totalDimensionsCites:104,book:{slug:"developments-in-corrosion-protection",title:"Developments in Corrosion Protection",fullTitle:"Developments in Corrosion Protection"},signatures:"Camila G. Dariva and Alexandre F. Galio",authors:[{id:"169261",title:"Dr.",name:"Camila",middleName:"G.",surname:"Dariva",slug:"camila-dariva",fullName:"Camila Dariva"},{id:"170138",title:"Dr.",name:"Alexandre",middleName:"Ferreira",surname:"Galio",slug:"alexandre-galio",fullName:"Alexandre Galio"}]}],mostDownloadedChaptersLast30Days:[{id:"60680",title:"Environmental Contamination by Heavy Metals",slug:"environmental-contamination-by-heavy-metals",totalDownloads:12290,totalCrossrefCites:66,totalDimensionsCites:115,book:{slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. Muedi",authors:[{id:"225304",title:"Dr.",name:"Vhahangwele",middleName:null,surname:"Masindi",slug:"vhahangwele-masindi",fullName:"Vhahangwele Masindi"},{id:"241403",title:"M.Sc.",name:"Khathutshelo",middleName:"Lilith",surname:"Muedi",slug:"khathutshelo-muedi",fullName:"Khathutshelo Muedi"}]},{id:"59905",title:"Synthesis of Silver Nanoparticles",slug:"synthesis-of-silver-nanoparticles",totalDownloads:5054,totalCrossrefCites:2,totalDimensionsCites:6,book:{slug:"silver-nanoparticles-fabrication-characterization-and-applications",title:"Silver Nanoparticles",fullTitle:"Silver Nanoparticles - Fabrication, Characterization and Applications"},signatures:"Remziye Güzel and Gülbahar Erdal",authors:[{id:"226613",title:"Dr.",name:"Remziye",middleName:null,surname:"Güzel",slug:"remziye-guzel",fullName:"Remziye Güzel"},{id:"240772",title:"MSc.",name:"Gülbahar",middleName:null,surname:"Erdal",slug:"gulbahar-erdal",fullName:"Gülbahar Erdal"}]},{id:"59857",title:"Introductory Chapter: Introducing Heavy Metals",slug:"introductory-chapter-introducing-heavy-metals",totalDownloads:4331,totalCrossrefCites:3,totalDimensionsCites:9,book:{slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Martin Koller and Hosam M. Saleh",authors:[{id:"144691",title:"Prof.",name:"Hosam",middleName:"M.",surname:"Saleh",slug:"hosam-saleh",fullName:"Hosam Saleh"}]},{id:"60518",title:"Synthetic Methods for Titanium Dioxide Nanoparticles: A Review",slug:"synthetic-methods-for-titanium-dioxide-nanoparticles-a-review",totalDownloads:3286,totalCrossrefCites:10,totalDimensionsCites:17,book:{slug:"titanium-dioxide-material-for-a-sustainable-environment",title:"Titanium Dioxide",fullTitle:"Titanium Dioxide - Material for a Sustainable Environment"},signatures:"Pardon Nyamukamba, Omobola Okoh, Henry Mungondori,\nRaymond Taziwa and Simcelile Zinya",authors:[{id:"196100",title:"Dr.",name:"Raymond",middleName:null,surname:"Taziwa",slug:"raymond-taziwa",fullName:"Raymond Taziwa"},{id:"219920",title:"Prof.",name:"Omobola",middleName:null,surname:"Okoh",slug:"omobola-okoh",fullName:"Omobola Okoh"},{id:"226567",title:"Dr.",name:"Pardon",middleName:null,surname:"Nyamukamba",slug:"pardon-nyamukamba",fullName:"Pardon Nyamukamba"},{id:"239758",title:"Mr.",name:"Simcelile",middleName:null,surname:"Zinya",slug:"simcelile-zinya",fullName:"Simcelile Zinya"}]},{id:"58868",title:"Iron Ore Pelletizing Process: An Overview",slug:"iron-ore-pelletizing-process-an-overview",totalDownloads:3186,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"iron-ores-and-iron-oxide-materials",title:"Iron Ores and Iron Oxide Materials",fullTitle:"Iron Ores and Iron Oxide Materials"},signatures:"Sandra Lúcia de Moraes, José Renato Baptista de Lima and Tiago\nRamos Ribeiro",authors:[{id:"216788",title:"Dr.",name:"Sandra",middleName:"Lúcia",surname:"De Moraes",slug:"sandra-de-moraes",fullName:"Sandra De Moraes"},{id:"233466",title:"Prof.",name:"José Renato Baptista",middleName:null,surname:"De Lima",slug:"jose-renato-baptista-de-lima",fullName:"José Renato Baptista De Lima"},{id:"233467",title:"MSc.",name:"Tiago Ramos",middleName:null,surname:"Ribeiro",slug:"tiago-ramos-ribeiro",fullName:"Tiago Ramos Ribeiro"}]},{id:"58797",title:"Green Corrosion Inhibitors, Past, Present, and Future",slug:"green-corrosion-inhibitors-past-present-and-future",totalDownloads:2788,totalCrossrefCites:5,totalDimensionsCites:7,book:{slug:"corrosion-inhibitors-principles-and-recent-applications",title:"Corrosion Inhibitors, Principles and Recent Applications",fullTitle:"Corrosion Inhibitors, Principles and Recent Applications"},signatures:"Omnia S. Shehata, Lobna A. Korshed and Adel Attia",authors:[{id:"220734",title:"Associate Prof.",name:"Omnia",middleName:null,surname:"Shehata",slug:"omnia-shehata",fullName:"Omnia Shehata"},{id:"227918",title:"Prof.",name:"Adel",middleName:null,surname:"Attia",slug:"adel-attia",fullName:"Adel Attia"},{id:"227919",title:"Dr.",name:"Lobna",middleName:null,surname:"Korshed",slug:"lobna-korshed",fullName:"Lobna Korshed"}]},{id:"51497",title:"The Review of Some Commonly Used Methods and Techniques to Measure the Thermal Conductivity of Insulation Materials",slug:"the-review-of-some-commonly-used-methods-and-techniques-to-measure-the-thermal-conductivity-of-insul",totalDownloads:4196,totalCrossrefCites:13,totalDimensionsCites:28,book:{slug:"insulation-materials-in-context-of-sustainability",title:"Insulation Materials in Context of Sustainability",fullTitle:"Insulation Materials in Context of Sustainability"},signatures:"Numan Yüksel",authors:[{id:"178245",title:"Dr.",name:"Numan",middleName:null,surname:"Yüksel",slug:"numan-yuksel",fullName:"Numan Yüksel"}]},{id:"70661",title:"Bioremediation Techniques for Polluted Environment: Concept, Advantages, Limitations, and Prospects",slug:"bioremediation-techniques-for-polluted-environment-concept-advantages-limitations-and-prospects",totalDownloads:195,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",title:"Trace Metals in the Environment",fullTitle:"Trace Metals in the Environment - New Approaches and Recent Advances"},signatures:"Indu Sharma",authors:[{id:"301262",title:"Associate Prof.",name:"Indu",middleName:null,surname:"Sharma",slug:"indu-sharma",fullName:"Indu Sharma"}]},{id:"47427",title:"Corrosion and Surface Treatment of Magnesium Alloys",slug:"corrosion-and-surface-treatment-of-magnesium-alloys",totalDownloads:3470,totalCrossrefCites:10,totalDimensionsCites:24,book:{slug:"magnesium-alloys-properties-in-solid-and-liquid-states",title:"Magnesium Alloys",fullTitle:"Magnesium Alloys - Properties in Solid and Liquid States"},signatures:"Henry Hu, Xueyuan Nie and Yueyu Ma",authors:[{id:"170745",title:"Prof.",name:"Henry",middleName:null,surname:"Hu",slug:"henry-hu",fullName:"Henry Hu"}]},{id:"58695",title:"Organic Corrosion Inhibitors",slug:"organic-corrosion-inhibitors",totalDownloads:3133,totalCrossrefCites:4,totalDimensionsCites:13,book:{slug:"corrosion-inhibitors-principles-and-recent-applications",title:"Corrosion Inhibitors, Principles and Recent Applications",fullTitle:"Corrosion Inhibitors, Principles and Recent Applications"},signatures:"Bogumił Eugeniusz Brycki, Iwona H. Kowalczyk, Adrianna Szulc,\nOlga Kaczerewska and Marta Pakiet",authors:[{id:"197271",title:"Prof.",name:"Bogumil E.",middleName:null,surname:"Brycki",slug:"bogumil-e.-brycki",fullName:"Bogumil E. Brycki"},{id:"207547",title:"Dr.",name:"Iwona",middleName:null,surname:"Kowalczyk",slug:"iwona-kowalczyk",fullName:"Iwona Kowalczyk"},{id:"207548",title:"Dr.",name:"Adrianna",middleName:null,surname:"Szulc",slug:"adrianna-szulc",fullName:"Adrianna Szulc"},{id:"207549",title:"Dr.",name:"Olga",middleName:null,surname:"Kaczerewska",slug:"olga-kaczerewska",fullName:"Olga Kaczerewska"},{id:"220728",title:"MSc.",name:"Marta",middleName:null,surname:"Pakiet",slug:"marta-pakiet",fullName:"Marta Pakiet"}]}],onlineFirstChaptersFilter:{topicSlug:"metals-and-nonmetals",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/101637/katarina-topalov",hash:"",query:{},params:{id:"101637",slug:"katarina-topalov"},fullPath:"/profiles/101637/katarina-topalov",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var t;(t=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(t)}()