List of some medicinal plants suggested for beneficial effects in cancer.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"},{slug:"intechopen-s-chapter-awarded-the-guenther-von-pannewitz-preis-2020-20200715",title:"IntechOpen's Chapter Awarded the Günther-von-Pannewitz-Preis 2020"},{slug:"suf-and-intechopen-announce-collaboration-20200331",title:"SUF and IntechOpen Announce Collaboration"}]},book:{item:{type:"book",id:"405",leadTitle:null,fullTitle:"Computational Simulations and Applications",title:"Computational Simulations and Applications",subtitle:null,reviewType:"peer-reviewed",abstract:"The purpose of this book is to introduce researchers and graduate students to a broad range of applications of computational simulations, with a particular emphasis on those involving computational fluid dynamics (CFD) simulations. The book is divided into three parts: Part I covers some basic research topics and development in numerical algorithms for CFD simulations, including Reynolds stress transport modeling, central difference schemes for convection-diffusion equations, and flow simulations involving simple geometries such as a flat plate or a vertical channel. Part II covers a variety of important applications in which CFD simulations play a crucial role, including combustion process and automobile engine design, fluid heat exchange, airborne contaminant dispersion over buildings and atmospheric flow around a re-entry capsule, gas-solid two phase flow in long pipes, free surface flow around a ship hull, and hydrodynamic analysis of electrochemical cells. Part III covers applications of non-CFD based computational simulations, including atmospheric optical communications, climate system simulations, porous media flow, combustion, solidification, and sound field simulations for optimal acoustic effects.",isbn:null,printIsbn:"978-953-307-430-6",pdfIsbn:"978-953-51-5558-4",doi:"10.5772/921",price:159,priceEur:175,priceUsd:205,slug:"computational-simulations-and-applications",numberOfPages:574,isOpenForSubmission:!1,isInWos:1,hash:"84a582eb7ec291ae468bc75d0fc9a101",bookSignature:"Jianping Zhu",publishedDate:"October 26th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/405.jpg",numberOfDownloads:70266,numberOfWosCitations:37,numberOfCrossrefCitations:17,numberOfDimensionsCitations:43,hasAltmetrics:0,numberOfTotalCitations:97,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 24th 2010",dateEndSecondStepPublish:"December 22nd 2010",dateEndThirdStepPublish:"April 28th 2011",dateEndFourthStepPublish:"May 28th 2011",dateEndFifthStepPublish:"July 27th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"62225",title:"Dr.",name:"Jianping",middleName:null,surname:"Zhu",slug:"jianping-zhu",fullName:"Jianping Zhu",profilePictureURL:"https://mts.intechopen.com/storage/users/62225/images/1785_n.jpg",biography:"Dr. Jianping Zhu received his Ph.D. in applied mathematics from the State University of New York at Stony Brook in 1990. He was on the faculty of the Department of Mathematics and Statistics at Mississippi State University from 1990 to 2001, and was chair of the Department of Theoretical and Applied Mathematics at the University of Akron from 2001 – 2005. Since 2005, he has been chair of the Department of Mathematics at the University of Texas at Arlington. His research interests are in the areas of numerical algorithms, computational simulations, and scientific computing. He received the second place award in the 1990 IBM Supercomputing Competition and the Intel Research Fellowship Award in 1992. He has written one book, edited two books, published over 80 refereed papers, and made 120 conference and colloquium presentations in 21 countries. He also served on the editorial boards of six international journals and numerous conference organizing committees. Over the last two decades, his research and education projects have been funded by over $6 million in grants from the USA federal agencies and industrial partners.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"The University of Texas at Arlington",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"599",title:"Computer Simulation",slug:"numerical-analysis-and-scientific-computing-computer-simulation"}],chapters:[{id:"21774",title:"Reynolds Stress Transport Modelling",doi:"10.5772/23171",slug:"reynolds-stress-transport-modelling",totalDownloads:8435,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Sharaf F. Al-Sharif",downloadPdfUrl:"/chapter/pdf-download/21774",previewPdfUrl:"/chapter/pdf-preview/21774",authors:[{id:"50900",title:"Dr.",name:"Sharaf",surname:"Al-Sharif",slug:"sharaf-al-sharif",fullName:"Sharaf Al-Sharif"}],corrections:null},{id:"21775",title:"Study of Some Key Issues for Applying LES to Real Engineering Problems",doi:"10.5772/24559",slug:"study-of-some-key-issues-for-applying-les-to-real-engineering-problems",totalDownloads:1539,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Xiaolong Yang",downloadPdfUrl:"/chapter/pdf-download/21775",previewPdfUrl:"/chapter/pdf-preview/21775",authors:[{id:"58145",title:"Prof.",name:"Xiaolong",surname:"Yang",slug:"xiaolong-yang",fullName:"Xiaolong Yang"}],corrections:null},{id:"21776",title:"An Introduction of Central Difference Scheme Stability for High Reynolds Number",doi:"10.5772/23442",slug:"an-introduction-of-central-difference-scheme-stability-for-high-reynolds-number",totalDownloads:2544,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"A. R. da Silva, A. Silveira-Neto and A. M. G. de Lima",downloadPdfUrl:"/chapter/pdf-download/21776",previewPdfUrl:"/chapter/pdf-preview/21776",authors:[{id:"52052",title:"Dr.",name:"Alice",surname:"Da Silva",slug:"alice-da-silva",fullName:"Alice Da Silva"},{id:"61762",title:"Dr.",name:"Aristeu",surname:"Silveira-Neto",slug:"aristeu-silveira-neto",fullName:"Aristeu Silveira-Neto"},{id:"61763",title:"Prof.",name:"Antonio Marcos Gonçalves",surname:"De Lima",slug:"antonio-marcos-goncalves-de-lima",fullName:"Antonio Marcos Gonçalves De Lima"}],corrections:null},{id:"21777",title:"A Fourth-Order Compact Finite Difference Scheme for Solving Unsteady Convection-Diffusion Equations",doi:"10.5772/25149",slug:"a-fourth-order-compact-finite-difference-scheme-for-solving-unsteady-convection-diffusion-equations",totalDownloads:6439,totalCrossrefCites:1,totalDimensionsCites:2,signatures:"Wenyuan Liao and Jianping Zhu",downloadPdfUrl:"/chapter/pdf-download/21777",previewPdfUrl:"/chapter/pdf-preview/21777",authors:[{id:"62225",title:"Dr.",name:"Jianping",surname:"Zhu",slug:"jianping-zhu",fullName:"Jianping Zhu"},{id:"62769",title:"Dr.",name:"Wenyuan",surname:"Liao",slug:"wenyuan-liao",fullName:"Wenyuan Liao"}],corrections:null},{id:"21778",title:"Internal Waves Radiation by a Turbulent Jet Flow in a Stratified Fluid",doi:"10.5772/23481",slug:"internal-waves-radiation-by-a-turbulent-jet-flow-in-a-stratified-fluid",totalDownloads:1673,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Oleg Druzhinin",downloadPdfUrl:"/chapter/pdf-download/21778",previewPdfUrl:"/chapter/pdf-preview/21778",authors:[{id:"52172",title:"Dr.",name:"Oleg",surname:"Druzhinin",slug:"oleg-druzhinin",fullName:"Oleg Druzhinin"}],corrections:null},{id:"21779",title:"Numerical Study on Flow Structures and Heat Transfer Characteristics of Turbulent Bubbly Upflow in a Vertical Channel",doi:"10.5772/24405",slug:"numerical-study-on-flow-structures-and-heat-transfer-characteristics-of-turbulent-bubbly-upflow-in-a",totalDownloads:1751,totalCrossrefCites:3,totalDimensionsCites:8,signatures:"Mitsuru Tanaka",downloadPdfUrl:"/chapter/pdf-download/21779",previewPdfUrl:"/chapter/pdf-preview/21779",authors:[{id:"57146",title:"Dr.",name:"Mitsuru",surname:"Tanaka",slug:"mitsuru-tanaka",fullName:"Mitsuru Tanaka"}],corrections:null},{id:"21780",title:"Mathematical Modelling of the Motion of Dust-Laden Gases in the Freeboard of CFB Using the Two-Fluid Approach",doi:"10.5772/24488",slug:"mathematical-modelling-of-the-motion-of-dust-laden-gases-in-the-freeboard-of-cfb-using-the-two-fluid",totalDownloads:1558,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Alexander Kartushinsky and Andres Siirde",downloadPdfUrl:"/chapter/pdf-download/21780",previewPdfUrl:"/chapter/pdf-preview/21780",authors:[{id:"57704",title:"Dr.",name:"Alexander",surname:"Kartushinsky",slug:"alexander-kartushinsky",fullName:"Alexander Kartushinsky"},{id:"60545",title:"Prof.",name:"Anders",surname:"Siirde",slug:"anders-siirde",fullName:"Anders Siirde"}],corrections:null},{id:"21781",title:"Computation of Non-Isothermal Reversed Stagnation-Point Flow over a Flat Plate",doi:"10.5772/23343",slug:"computation-of-non-isothermal-reversed-stagnation-point-flow-over-a-flat-plate",totalDownloads:1703,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Vai Kuong Sin and Chon Kit Chio",downloadPdfUrl:"/chapter/pdf-download/21781",previewPdfUrl:"/chapter/pdf-preview/21781",authors:[{id:"51648",title:"Dr.",name:"Vai Kuong",surname:"Sin",slug:"vai-kuong-sin",fullName:"Vai Kuong Sin"},{id:"68251",title:"BSc",name:"Chon Kit",surname:"Chio",slug:"chon-kit-chio",fullName:"Chon Kit Chio"}],corrections:null},{id:"21782",title:"Numerical Modelling and Optimization of the Mixture Formation Processby Multi-Hole Injectors in a GDI Engine",doi:"10.5772/16547",slug:"numerical-modelling-and-optimization-of-the-mixture-formation-processby-multi-hole-injectors-in-a-gd",totalDownloads:3588,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Michela Costa and Luigi Allocca",downloadPdfUrl:"/chapter/pdf-download/21782",previewPdfUrl:"/chapter/pdf-preview/21782",authors:[{id:"10031",title:"Dr.",name:"Michela",surname:"Costa",slug:"michela-costa",fullName:"Michela Costa"},{id:"47843",title:"Dr.",name:"Luigi",surname:"Allocca",slug:"luigi-allocca",fullName:"Luigi Allocca"}],corrections:null},{id:"21783",title:"Turbulent Combustion Simulation by Large Eddy Simulation and Direct Numerical Simulation",doi:"10.5772/25165",slug:"turbulent-combustion-simulation-by-large-eddy-simulation-and-direct-numerical-simulation",totalDownloads:1972,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Fang Wang",downloadPdfUrl:"/chapter/pdf-download/21783",previewPdfUrl:"/chapter/pdf-preview/21783",authors:[{id:"13674",title:"Prof.",name:"Fang",surname:"Wang",slug:"fang-wang",fullName:"Fang Wang"}],corrections:null},{id:"21784",title:"Numerical Simulation of Dense Gas-Solid Multiphase Flows Using Eulerian-Eulerian Two-Fluid Model",doi:"10.5772/24244",slug:"numerical-simulation-of-dense-gas-solid-multiphase-flows-using-eulerian-eulerian-two-fluid-model",totalDownloads:3508,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Teklay Weldeabzgi Asegehegn, Matthias Schreiber and Hans Joachim Krautz",downloadPdfUrl:"/chapter/pdf-download/21784",previewPdfUrl:"/chapter/pdf-preview/21784",authors:[{id:"56273",title:"Mr",name:"Teklay",surname:"Asegehegn",slug:"teklay-asegehegn",fullName:"Teklay Asegehegn"},{id:"61986",title:"Mr",name:"Matthias",surname:"Schreiber",slug:"matthias-schreiber",fullName:"Matthias Schreiber"},{id:"61987",title:"Prof.",name:"Hans",surname:"Krautz",slug:"hans-krautz",fullName:"Hans Krautz"}],corrections:null},{id:"21785",title:"Numerical Simulation Techniques for the Prediction of Fluid-Dynamics, Combustion and Performance in IC Engines Fuelled by CNG",doi:"10.5772/25081",slug:"numerical-simulation-techniques-for-the-prediction-of-fluid-dynamics-combustion-and-performance-in-i",totalDownloads:3100,totalCrossrefCites:4,totalDimensionsCites:4,signatures:"Mirko Baratta and Ezio Spessa",downloadPdfUrl:"/chapter/pdf-download/21785",previewPdfUrl:"/chapter/pdf-preview/21785",authors:[{id:"61664",title:"Prof.",name:"Ezio",surname:"Spessa",slug:"ezio-spessa",fullName:"Ezio Spessa"},{id:"61671",title:"Dr.",name:"Mirko",surname:"Baratta",slug:"mirko-baratta",fullName:"Mirko Baratta"}],corrections:null},{id:"21786",title:"Development of Two-Phase Flow Correlation for Fluid Mixing Phenomena in Boiling Water Reactor",doi:"10.5772/24557",slug:"development-of-two-phase-flow-correlation-for-fluid-mixing-phenomena-in-boiling-water-reactor",totalDownloads:2129,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Hiroyuki Yoshida and Kazuyuki Takase",downloadPdfUrl:"/chapter/pdf-download/21786",previewPdfUrl:"/chapter/pdf-preview/21786",authors:[{id:"58130",title:"Dr.",name:"Hiroyuki",surname:"Yoshida",slug:"hiroyuki-yoshida",fullName:"Hiroyuki Yoshida"},{id:"62143",title:"Dr.",name:"Kazuyuki",surname:"Takase",slug:"kazuyuki-takase",fullName:"Kazuyuki Takase"}],corrections:null},{id:"21787",title:"Numerical Simulations of Unsteady Fluid Forces in Heat Exchanger Tube Bundles",doi:"10.5772/25404",slug:"numerical-simulations-of-unsteady-fluid-forces-in-heat-exchanger-tube-bundles",totalDownloads:2268,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"H. Omar, M. Hassan and A. Gerber",downloadPdfUrl:"/chapter/pdf-download/21787",previewPdfUrl:"/chapter/pdf-preview/21787",authors:[{id:"63215",title:"Dr.",name:"Hossin",surname:"Omar",slug:"hossin-omar",fullName:"Hossin Omar"},{id:"106914",title:"Dr.",name:"Marwan",surname:"Hassan",slug:"marwan-hassan",fullName:"Marwan Hassan"},{id:"106916",title:"Prof.",name:"Andrew",surname:"Gerber",slug:"andrew-gerber",fullName:"Andrew Gerber"}],corrections:null},{id:"21788",title:"Large-Eddy Simulation of Turbulent Flow and Plume Dispersion in a Spatially-Developing Turbulent Boundary Layer Flow",doi:"10.5772/23276",slug:"large-eddy-simulation-of-turbulent-flow-and-plume-dispersion-in-a-spatially-developing-turbulent-bou",totalDownloads:2179,totalCrossrefCites:1,totalDimensionsCites:1,signatures:"Hiromasa Nakayama",downloadPdfUrl:"/chapter/pdf-download/21788",previewPdfUrl:"/chapter/pdf-preview/21788",authors:[{id:"51377",title:"Dr.",name:"Hiromasa",surname:"Nakayama",slug:"hiromasa-nakayama",fullName:"Hiromasa Nakayama"}],corrections:null},{id:"21789",title:"Computations of Flowfield over Reentry Modules at High Speed",doi:"10.5772/24259",slug:"computations-of-flowfield-over-reentry-modules-at-high-speed",totalDownloads:3426,totalCrossrefCites:0,totalDimensionsCites:3,signatures:"R. C. Mehta",downloadPdfUrl:"/chapter/pdf-download/21789",previewPdfUrl:"/chapter/pdf-preview/21789",authors:[{id:"56358",title:"Dr.",name:"R. C.",surname:"Mehta",slug:"r.-c.-mehta",fullName:"R. C. Mehta"}],corrections:null},{id:"21790",title:"Numerical Simulation of Dense Phase Pneumatic Conveying in Long-Distance Pipe",doi:"10.5772/25200",slug:"numerical-simulation-of-dense-phase-pneumatic-conveying-in-long-distance-pipe",totalDownloads:5359,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Zongming Liu, Guangbin Duan and Kun Wang",downloadPdfUrl:"/chapter/pdf-download/21790",previewPdfUrl:"/chapter/pdf-preview/21790",authors:[{id:"62481",title:"Prof.",name:"Zongming",surname:"Liu",slug:"zongming-liu",fullName:"Zongming Liu"},{id:"136419",title:"Dr.",name:"Guangbin",surname:"Duan",slug:"guangbin-duan",fullName:"Guangbin Duan"},{id:"136422",title:"Prof.",name:"Kun",surname:"Wang",slug:"kun-wang",fullName:"Kun Wang"}],corrections:null},{id:"21791",title:"A Three-Dimensional Numerical Simulation of the Free Surface Flow Around a Ship Hull",doi:"10.5772/24501",slug:"a-three-dimensional-numerical-simulation-of-the-free-surface-flow-around-a-ship-hull",totalDownloads:2208,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"J. B. V. Wanderley, M. Vitola, S. H. Sphaier and C. Levi",downloadPdfUrl:"/chapter/pdf-download/21791",previewPdfUrl:"/chapter/pdf-preview/21791",authors:[{id:"57804",title:"Dr.",name:"Juan",surname:"B. V. Wanderley",slug:"juan-b.-v.-wanderley",fullName:"Juan B. V. Wanderley"},{id:"123701",title:"Dr.",name:"Marcelo",surname:"Vitola",slug:"marcelo-vitola",fullName:"Marcelo Vitola"},{id:"123703",title:"Prof.",name:"Sergio",surname:"Sphaier",slug:"sergio-sphaier",fullName:"Sergio Sphaier"},{id:"123704",title:"Prof.",name:"Carlos",surname:"Levi",slug:"carlos-levi",fullName:"Carlos Levi"}],corrections:null},{id:"21792",title:"Hydrodynamic Analysis of Electrochemical Cells",doi:"10.5772/23218",slug:"hydrodynamic-analysis-of-electrochemical-cells",totalDownloads:2430,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"Cesar Augusto Real-Ramirez and Jesus Isidro Gonzalez-Trejo",downloadPdfUrl:"/chapter/pdf-download/21792",previewPdfUrl:"/chapter/pdf-preview/21792",authors:[{id:"51156",title:"Dr.",name:"Cesar",surname:"Real-Ramirez",slug:"cesar-real-ramirez",fullName:"Cesar Real-Ramirez"},{id:"51343",title:"Dr.",name:"Jesus Isidro",surname:"Gonzalez-Trejo",slug:"jesus-isidro-gonzalez-trejo",fullName:"Jesus Isidro Gonzalez-Trejo"}],corrections:null},{id:"21793",title:"Upper Burst Error Bound for Atmospheric Correlated Optical Communications Using an Alternative Matrix Decomposition",doi:"10.5772/24119",slug:"upper-burst-error-bound-for-atmospheric-correlated-optical-communications-using-an-alternative-matri",totalDownloads:1512,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Antonio Jurado-Navas, José María Garrido-Balsells, Miguel Castillo-Vázquez and Antonio Puerta-Notario",downloadPdfUrl:"/chapter/pdf-download/21793",previewPdfUrl:"/chapter/pdf-preview/21793",authors:[{id:"55578",title:"Dr.",name:"Antonio",surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas"},{id:"60012",title:"Dr.",name:"José María",surname:"Garrido-Balsells",slug:"jose-maria-garrido-balsells",fullName:"José María Garrido-Balsells"},{id:"60013",title:"Dr.",name:"Miguel",surname:"Castillo-Vazquez",slug:"miguel-castillo-vazquez",fullName:"Miguel Castillo-Vazquez"},{id:"60014",title:"Prof.",name:"Antonio",surname:"Puerta-Notario",slug:"antonio-puerta-notario",fullName:"Antonio Puerta-Notario"}],corrections:null},{id:"21794",title:"Climate System Simulations: An Integrated, Multi-Scale Approach for Research and Decision-Making",doi:"10.5772/24229",slug:"climate-system-simulations-an-integrated-multi-scale-approach-for-research-and-decision-making",totalDownloads:1628,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Ángel G. Muñoz, Alfredo Nuñez and Ramón J. Cova",downloadPdfUrl:"/chapter/pdf-download/21794",previewPdfUrl:"/chapter/pdf-preview/21794",authors:[{id:"56219",title:"Dr.",name:"Ramón",surname:"Cova",slug:"ramon-cova",fullName:"Ramón Cova"},{id:"99327",title:"Prof.",name:"Ángel G.",surname:"Muñoz",slug:"angel-g.-munoz",fullName:"Ángel G. Muñoz"},{id:"99328",title:"Mr.",name:"Alfredo",surname:"Nunez",slug:"alfredo-nunez",fullName:"Alfredo Nunez"}],corrections:null},{id:"21795",title:"The Effect of Tomography Imaging Artefacts on Structural Analysis and Numerical Permeability Simulations",doi:"10.5772/24306",slug:"the-effect-of-tomography-imaging-artefacts-on-structural-analysis-and-numerical-permeability-simulat",totalDownloads:2478,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Viivi Koivu and Tuomas Turpeinen",downloadPdfUrl:"/chapter/pdf-download/21795",previewPdfUrl:"/chapter/pdf-preview/21795",authors:[{id:"56586",title:"Dr.",name:"Viivi",surname:"Koivu",slug:"viivi-koivu",fullName:"Viivi Koivu"},{id:"60276",title:"MSc",name:"Tuomas",surname:"Turpeinen",slug:"tuomas-turpeinen",fullName:"Tuomas Turpeinen"}],corrections:null},{id:"21796",title:"Nongray EWB and WSGG Radiation Modeling in Oxy-Fuel Environments",doi:"10.5772/24669",slug:"nongray-ewb-and-wsgg-radiation-modeling-in-oxy-fuel-environments",totalDownloads:2649,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"Osama A. Marzouk and E. David Huckaby",downloadPdfUrl:"/chapter/pdf-download/21796",previewPdfUrl:"/chapter/pdf-preview/21796",authors:[{id:"58820",title:"Dr.",name:"Osama",surname:"Marzouk",slug:"osama-marzouk",fullName:"Osama Marzouk"},{id:"62179",title:"Mr.",name:"E David",surname:"Huckaby",slug:"e-david-huckaby",fullName:"E David Huckaby"}],corrections:null},{id:"21797",title:"Numerical Modeling of Solidification Process",doi:"10.5772/24496",slug:"numerical-modeling-of-solidification-process",totalDownloads:2477,totalCrossrefCites:5,totalDimensionsCites:14,signatures:"Bohdan Mochnacki",downloadPdfUrl:"/chapter/pdf-download/21797",previewPdfUrl:"/chapter/pdf-preview/21797",authors:[{id:"57756",title:"Dr.",name:"Bohdan",surname:"Mochnacki",slug:"bohdan-mochnacki",fullName:"Bohdan Mochnacki"}],corrections:null},{id:"21798",title:"Performance Evaluation of Adaptive Algorithms for Wave Field Analysis/Synthesis Using Sound Field Simulations",doi:"10.5772/24513",slug:"performance-evaluation-of-adaptive-algorithms-for-wave-field-analysis-synthesis-using-sound-field-si",totalDownloads:1715,totalCrossrefCites:2,totalDimensionsCites:3,signatures:"Paolo Peretti, Stefania Cecchi, Laura Romoli and Francesco Piazza",downloadPdfUrl:"/chapter/pdf-download/21798",previewPdfUrl:"/chapter/pdf-preview/21798",authors:[{id:"57865",title:"Dr",name:"Paolo",surname:"Peretti",slug:"paolo-peretti",fullName:"Paolo Peretti"},{id:"62002",title:"Dr.",name:"Stefania",surname:"Cecchi",slug:"stefania-cecchi",fullName:"Stefania Cecchi"},{id:"62003",title:"Dr.",name:"Laura",surname:"Romoli",slug:"laura-romoli",fullName:"Laura Romoli"},{id:"62004",title:"Prof.",name:"Francesco",surname:"Piazza",slug:"francesco-piazza",fullName:"Francesco Piazza"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"1485",title:"Applications of Monte Carlo Method in Science and Engineering",subtitle:null,isOpenForSubmission:!1,hash:"08abe20f1549c83cfb208c83e12ee7df",slug:"applications-of-monte-carlo-method-in-science-and-engineering",bookSignature:"Shaul Mordechai",coverURL:"https://cdn.intechopen.com/books/images_new/1485.jpg",editedByType:"Edited by",editors:[{id:"21994",title:"Prof.",name:"Shaul",surname:"Mordechai",slug:"shaul-mordechai",fullName:"Shaul Mordechai"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editedByType:"Edited by",editors:[{id:"12289",title:"Prof.",name:"Vasilios",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3036",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 2",isOpenForSubmission:!1,hash:"39d85d5d566c24744e4ac69fc297bb36",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-2",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/3036.jpg",editedByType:"Edited by",editors:[{id:"12289",title:"Prof.",name:"Vasilios",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1025",title:"Engineering Education and Research Using MATLAB",subtitle:null,isOpenForSubmission:!1,hash:"6e4cf9f0e6d7dccba13bc8edc4bf8e70",slug:"engineering-education-and-research-using-matlab",bookSignature:"Ali H. Assi",coverURL:"https://cdn.intechopen.com/books/images_new/1025.jpg",editedByType:"Edited by",editors:[{id:"12279",title:"Dr.",name:"Ali",surname:"Assi",slug:"ali-assi",fullName:"Ali Assi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1027",title:"Applications of MATLAB in Science and Engineering",subtitle:null,isOpenForSubmission:!1,hash:"64f208a73ca0da9038418788e86dfe28",slug:"applications-of-matlab-in-science-and-engineering",bookSignature:"Tadeusz Michałowski",coverURL:"https://cdn.intechopen.com/books/images_new/1027.jpg",editedByType:"Edited by",editors:[{id:"35273",title:"Prof.",name:"Tadeusz",surname:"Michalowski",slug:"tadeusz-michalowski",fullName:"Tadeusz Michalowski"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3037",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 3",isOpenForSubmission:!1,hash:"1de63ac4f2c398a1304a7c08ee883655",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-3",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/3037.jpg",editedByType:"Edited by",editors:[{id:"12289",title:"Prof.",name:"Vasilios",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1026",title:"MATLAB for Engineers",subtitle:"Applications in Control, Electrical Engineering, IT and Robotics",isOpenForSubmission:!1,hash:"81f855a543e6deaabe4b7cd8f5fae020",slug:"matlab-for-engineers-applications-in-control-electrical-engineering-it-and-robotics",bookSignature:"Karel Perutka",coverURL:"https://cdn.intechopen.com/books/images_new/1026.jpg",editedByType:"Edited by",editors:[{id:"11909",title:"Dr.",name:"Karel",surname:"Perutka",slug:"karel-perutka",fullName:"Karel Perutka"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5323",title:"Modeling and Simulation in Engineering Sciences",subtitle:null,isOpenForSubmission:!1,hash:"684a6db4422b067b280c33faf661d747",slug:"modeling-and-simulation-in-engineering-sciences",bookSignature:"Noreen Sher Akbar and O. Anwar Beg",coverURL:"https://cdn.intechopen.com/books/images_new/5323.jpg",editedByType:"Edited by",editors:[{id:"184401",title:"Dr.",name:"Noreen",surname:"Sher Akbar",slug:"noreen-sher-akbar",fullName:"Noreen Sher Akbar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2830",title:"Advances in Modeling of Fluid Dynamics",subtitle:null,isOpenForSubmission:!1,hash:"63b0031c4189b213e315fe50e17bab66",slug:"advances-in-modeling-of-fluid-dynamics",bookSignature:"Chaoqun Liu",coverURL:"https://cdn.intechopen.com/books/images_new/2830.jpg",editedByType:"Edited by",editors:[{id:"143219",title:"Dr.",name:"Chaoqun",surname:"Liu",slug:"chaoqun-liu",fullName:"Chaoqun Liu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3756",title:"Discrete Event Simulations",subtitle:null,isOpenForSubmission:!1,hash:"e9f24c7c9f97e73f3045a0f71a760745",slug:"discrete-event-simulations",bookSignature:"Aitor Goti",coverURL:"https://cdn.intechopen.com/books/images_new/3756.jpg",editedByType:"Edited by",editors:[{id:"10806",title:"Dr.",name:"Aitor",surname:"Goti",slug:"aitor-goti",fullName:"Aitor Goti"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"59773",slug:"corrigendum-to-systematic-study-of-ethylene-vinyl-acetate-eva-in-the-manufacturing-of-protector-devi",title:"Corrigendum to: Systematic Study of Ethylene-Vinyl Acetate (EVA) in the Manufacturing of Protector Devices for the Orofacial System",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/59773.pdf",downloadPdfUrl:"/chapter/pdf-download/59773",previewPdfUrl:"/chapter/pdf-preview/59773",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/59773",risUrl:"/chapter/ris/59773",chapter:{id:"56614",slug:"systematic-study-of-ethylene-vinyl-acetate-eva-in-the-manufacturing-of-protector-devices-for-the-oro",signatures:"Reinaldo Brito e Dias, Neide Pena Coto, Gilmar Ferreira Batalha and\nLarissa Driemeier",dateSubmitted:"January 25th 2017",dateReviewed:"May 31st 2017",datePrePublished:null,datePublished:"February 14th 2018",book:{id:"5951",title:"Biomaterials in Regenerative Medicine",subtitle:null,fullTitle:"Biomaterials in Regenerative Medicine",slug:"biomaterials-in-regenerative-medicine",publishedDate:"February 14th 2018",bookSignature:"Leszek A. Dobrzański",coverURL:"https://cdn.intechopen.com/books/images_new/5951.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"15880",title:"Prof.",name:"Leszek A.",middleName:null,surname:"Dobrzański",slug:"leszek-a.-dobrzanski",fullName:"Leszek A. Dobrzański"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"204968",title:"Dr.",name:"Neide",middleName:null,surname:"Pena Coto",fullName:"Neide Pena Coto",slug:"neide-pena-coto",email:"neidecoto@gmail.com",position:null,institution:null}]}},chapter:{id:"56614",slug:"systematic-study-of-ethylene-vinyl-acetate-eva-in-the-manufacturing-of-protector-devices-for-the-oro",signatures:"Reinaldo Brito e Dias, Neide Pena Coto, Gilmar Ferreira Batalha and\nLarissa Driemeier",dateSubmitted:"January 25th 2017",dateReviewed:"May 31st 2017",datePrePublished:null,datePublished:"February 14th 2018",book:{id:"5951",title:"Biomaterials in Regenerative Medicine",subtitle:null,fullTitle:"Biomaterials in Regenerative Medicine",slug:"biomaterials-in-regenerative-medicine",publishedDate:"February 14th 2018",bookSignature:"Leszek A. Dobrzański",coverURL:"https://cdn.intechopen.com/books/images_new/5951.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"15880",title:"Prof.",name:"Leszek A.",middleName:null,surname:"Dobrzański",slug:"leszek-a.-dobrzanski",fullName:"Leszek A. Dobrzański"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"204968",title:"Dr.",name:"Neide",middleName:null,surname:"Pena Coto",fullName:"Neide Pena Coto",slug:"neide-pena-coto",email:"neidecoto@gmail.com",position:null,institution:null}]},book:{id:"5951",title:"Biomaterials in Regenerative Medicine",subtitle:null,fullTitle:"Biomaterials in Regenerative Medicine",slug:"biomaterials-in-regenerative-medicine",publishedDate:"February 14th 2018",bookSignature:"Leszek A. Dobrzański",coverURL:"https://cdn.intechopen.com/books/images_new/5951.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"15880",title:"Prof.",name:"Leszek A.",middleName:null,surname:"Dobrzański",slug:"leszek-a.-dobrzanski",fullName:"Leszek A. Dobrzański"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"9731",leadTitle:null,title:"Oxidoreductase",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tIt has been said that oxidation- reduction(redox) reactions are the foundation of life – an accurate reflection in that much of cellular anabolic and catabolic metabolism is based on enzyme-catalyzed redox reactions. Oxidoreductases consist of a huge class of enzymes catalyzing the electrons transfer from an electron donor (reductant) to an electron acceptor (oxidant) molecule, taking several co-factors as nicotinamide adenine dinucleotide phosphate (NADP) or nicotinamide adenine dinucleotide (NAD) or Flavin dinucleotide (FAD). As there are several chemical and biochemical transformations reactions that comprise oxidation/reduction processes, it has long been an important goal in biotechnology to develop applications of oxidoreductases enzymes. During the last few years, significant breakthrough has been made in the development of oxidoreductase-based diagnostic tests. The proper names of oxidoreductases are in a form of "donor:acceptor oxidoreductase"; while in most cases "donor dehydrogenase" is much more common. Common names also sometimes appeared as "acceptor reductase", such as NAD+ reductase. "Donor oxidase" is a special case when O2 serves as the acceptor.
\r\n\r\n\tOxidoreductase have several functions. Oxidoreductase enzymes play significant roles in both aerobic and anaerobic metabolism. They have an important role in biological procedures like glycolysis, TCA cycle, oxidative phosphorylation, and amino acid metabolism. In glycolysis, glyceraldehydes-3-phosphate dehydrogenase accelerates the reduction of NAD+ to NADH in aerobic and anaerobic conditions. However, the re-oxidization of the generated NADH to NAD+ occurs in the oxidative phosphorylation pathway in order to maintain the redox state of the cell. In addition, during anaerobic glycolysis, the oxidation of NADH is accomplished through the reduction of pyruvate to lactate. The glycolysis product pyruvate takes part in the TCA cycle in a form of acetyl-CoA. Moreover, the pyruvate is further oxidized in the TCA cycle. All twenty of the amino acids, except for leucine and lysine, can be degraded to intermediates in TCA cycle, which allows the carbon skeletons of the amino acids to be converted into oxaloacetate and subsequently into pyruvate. The gluconeogenic pathway can then exploit the formed pyruvate.
",isbn:"978-1-83880-901-0",printIsbn:"978-1-83880-900-3",pdfIsbn:"978-1-83880-902-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",bookSignature:"Prof. Mahmoud Ahmed Mansour",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",keywords:"Oxidoreductase, Oxidoreduction Reactions, Oxidant, Reductant, Cofactors, Enzyme Structure, Enzyme Kinetics, Temperature, Purification, Applications of Oxidoreductases, Free Radicals, Diseases",numberOfDownloads:366,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 14th 2020",dateEndSecondStepPublish:"September 10th 2020",dateEndThirdStepPublish:"November 9th 2020",dateEndFourthStepPublish:"January 28th 2021",dateEndFifthStepPublish:"March 29th 2021",remainingDaysToSecondStep:"4 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Mansour obtained his PhD from Karolinska Institute and Al-Azhar University and is currently working as Professor at King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. Dr. Mansour received State Encouragement award from Scientific Research Academy.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour",profilePictureURL:"https://mts.intechopen.com/storage/users/224662/images/system/224662.jpg",biography:"Mahmoud Mansour PhD, is a professor of Biochemistry at Pharmaceutical Sciences Department, College of Pharmacy King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia. His specialization includes molecular biology, biochemical pharmacology, pharmacogenetics and biochemistry. His research fields are biochemical pharmacological studies in cancers (especially hepatic cancer), antioxidants, oxidative stress, proteasome (and its role in the treatment of hepatic cancer), experimental gastroenterology, clinical gastroenterology and diabetes. He published more than 60 papers in peer-reviewed journals. He received State Encouragement award from Scientific Research Academy, (1998). Fourteen of his students were appointed as full university professors in Egypt, and Saudi Arabia.",institutionString:"King Saud bin Abdulaziz University for Health Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"King Saud bin Abdulaziz University for Health Sciences",institutionURL:null,country:{name:"Saudi Arabia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"}],chapters:[{id:"73576",title:"Oxidoreductases: Significance for Humans and Microorganism",slug:"oxidoreductases-significance-for-humans-and-microorganism",totalDownloads:75,totalCrossrefCites:0,authors:[null]},{id:"73110",title:"Biological Application and Disease of Oxidoreductase Enzymes",slug:"biological-application-and-disease-of-oxidoreductase-enzymes",totalDownloads:93,totalCrossrefCites:0,authors:[null]},{id:"73831",title:"Applications of Oxidoreductases",slug:"applications-of-oxidoreductases",totalDownloads:69,totalCrossrefCites:0,authors:[null]},{id:"73142",title:"Role of Subcellular ROS in Providing Resilience to Vascular Endothelium",slug:"role-of-subcellular-ros-in-providing-resilience-to-vascular-endothelium",totalDownloads:55,totalCrossrefCites:0,authors:[null]},{id:"73905",title:"Bulk and Nanocatalysts Applications in Advanced Oxidation Processes",slug:"bulk-and-nanocatalysts-applications-in-advanced-oxidation-processes",totalDownloads:64,totalCrossrefCites:0,authors:[null]},{id:"73434",title:"The Impact of Oxidoreductases-Related MicroRNAs in Glucose Metabolism of Renal Cell Carcinoma and Prostate Cancer",slug:"the-impact-of-oxidoreductases-related-micrornas-in-glucose-metabolism-of-renal-cell-carcinoma-and-pr",totalDownloads:10,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270941",firstName:"Sandra",lastName:"Maljavac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270941/images/7824_n.jpg",email:"sandra.m@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:"6966",title:"Lipid Peroxidation Research",subtitle:null,isOpenForSubmission:!1,hash:"f1f45176e765ecb65a1c6d1496e75b5b",slug:"lipid-peroxidation-research",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/6966.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6694",title:"New Trends in Ion Exchange Studies",subtitle:null,isOpenForSubmission:!1,hash:"3de8c8b090fd8faa7c11ec5b387c486a",slug:"new-trends-in-ion-exchange-studies",bookSignature:"Selcan Karakuş",coverURL:"https://cdn.intechopen.com/books/images_new/6694.jpg",editedByType:"Edited by",editors:[{id:"206110",title:"Dr.",name:"Selcan",surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"54745",title:"Lycopene: Multitargeted Applications in Cancer Therapy",doi:"10.5772/68131",slug:"lycopene-multitargeted-applications-in-cancer-therapy",body:'\nNatural products, which can be defined as simple or complex molecules (primary and secondary metabolites) produced naturally by any organism, constitute a diverse group of substances some of which are part of our food, and others have medicinal properties. Over the past few decades, there has been a tremendous increase in research on isolation and purification of compounds of botanical origin and establishing the efficacy of these compounds as potential therapeutic and preventive agents. The natural products have received considerable attention as potential drugs, and a large number of medicinal plants and their formulations have been investigated and found useful in cancer chemotherapy [1]. According to an estimate, more than half of potent anticancer drugs have natural product origin [2]. Some of the plant species that have been used for medicinal purpose and suggested for their beneficial effect in cancer are listed in Table 1.
\nPlant species | \nPreparation | \nEffect |
---|---|---|
Acacia nilotica | \nAqueous extracts of bark, gum, flower, and leaves | \nEffective in chemically-induced hepatocellular carcinoma (HCC) [3] and skin papillomagenesis [4] |
Aegle marmelos | \nHydro-alcoholic extract of leaf | \nRemission in Ehlirch ascites carcinoma (EAC) [5] |
Aloe vera | \nExtract | \nSkin carcinoma [6] |
Alstonia scholaris | \nAlkaloid fraction from bark | \nUV-induced carcinogenesis [7], DMBA-induced skin carcinogenesis [8] and UV-induced hematological disorder [9] |
Azadirchata indica | \nEthyl acetate and methanolic fractions of the leaves | \nDMBA-induced mammary carcinogenesis [10] and prostate cancer [11] |
Biophytum sensitivum | \nAlcoholic extract | \nDalton’s lymphoma ascites (DLA) and EAC [12] |
Boswellia serrata | \nTriterpenediol preparation | \nCaspase-8 activation and apoptosis [13] |
Butea monosperma | \nFlower extract | \nLiver cancer [14] |
Cassia auriculata | \nleaf extract | \nDecrease Bcl-2/Bax ratio [15] |
Cassia occidentalis | \nAqueous extracts | \nInhibit growth of HCT-15, SW-620, PC-3, MCF-7, SiHa and OVCAR-5 cancer cells [16] |
Cassia tora | \nMethanolic extract | \nEnhance caspase-3 activity of HeLa cells [17] |
Cedrus deodara | \nLignan mixture | \nEffect on leukemia cells [18] |
Cheilanthes farinose | \nFern | \nHCC [19] |
Cinnamomum cassia | \n\n | Cervical cancer cells (SiHa) [20] |
Garcinia indica | \nMethanolic extract | \nColon, breast and liver cancer [21] |
Inula racemosa | \nEthanolic extract of roots | \nColon, ovary, prostate, lung, CNS and leukemia cells [22] |
Lygodium flexuosum | \nExtract | \nInduce apoptosis in hepatoma cells [23] |
Ocimum viride | \nEssential oils | \nColorectal adenocarcinoma [24] |
Oryza sativa | \nMethanolic extracts | \nC6 glioma cells [25] |
Phyllanthus niruri | \nHydro-alcoholic extract | \nSkin carcinoma [26] |
Piper longum | \nMethanolic extract | \nColon cancer [27] |
Polyalthia longifolia | \nEthanolic stem, bark and leave extracts | \nEAC and DLA [28] |
Rhodiola imbricate | \nAqueous extract | \nIncrease ROS and arrest cell cycle progression at G2/M phase in K562 cells [29] |
Semecarpus anacardium | \nNut milk extract | \nEffect on leukemic cells from the bone marrow [30], induce apoptosis in breast cancer cells through mitochondria mediated apoptosis [31] |
Sesbania grandiflora | \nSesbania fraction 2, extracted from the flower | \nDown-regulate NF-kB, Bcl-2, p-Akt, cyclooxygenase-2, inhibits proliferation and induced apoptosis in DLA and SW-480 cells [32] |
Terminalia arjuna | \nEthanolic extract | \nLiver cancer [33] |
Tinospora cordifolia | \nExtract | \nAntitumor and chemopreventive [34] |
Trachyspermum ammi | \nSeed extract | \nSkin and forestomach tumor multiplicity [35] |
Withania somnifera | \nHydro-alcoholic extract | \nColon cancer model [36], cell cycle disruption and antiangiogenic, property [37] |
Zingiber officinale | \nExtract | \nSuppressed cell proliferation [38] |
List of some medicinal plants suggested for beneficial effects in cancer.
Natural substances such as paclitaxel [39], alkaloids and other substances [1] have demonstrated encouraging antitumor activity in human cancer cells in vivo and in vitro. These molecules act by a variety of mechanisms. For example, paclitaxel, a complex diterpene having a taxane ring with a four-membered oxetane ring and an ester side chain at position C-13, enhances the polymerization of tubulin to stable microtubules and also interacts directly with the microtubules [39]. Other mechanisms of action of antitumor agents include the inhibition of S phase-specific topoisomerase-I (camptothecin) and S and G2 phase-specific topoisomerase-II (etoposide), blockade of G2/M and M/G1 check points (paclitaxel), and prevention of microtubule depolymerization (vinblastine). A new class, commonly known as the vascular disrupting agents (VDA) (e.g., combretastatin A4 phosphate), targets tumor blood vessels. Combretastatin A4 phosphate is a VAD isolated from Combretum caffrum and has been reported to be antimitotic and antiangiogenic, along with the microtubule-depolymerizing property [40]. Substances like berberine, a protoberberine alkaloid found in the roots, rhizomes, stems and bark of berberis, goldenseal (Hydrastis canadensis) and Coptis chinensis, have also been reported to inhibit different types of cancer [41–49]. They act by inhibiting angiogenesis and by other mechanisms in different cancer models. Mahanine, a purified lead molecule derived from the leaves of Murraya koenigii, which showed antiproliferative activity in leukemic cells, primary cells of leukemic and myeloid patients and inhibited K562 xenograft growth, activates reactive oxygen species (ROS)-mediated mitochondrial apoptotic pathway, death receptor-mediated signaling differentially in MOLT-3 and K562 cells. Piper betle, reported to decrease the mitochondrial membrane potential and induce apoptosis in primary leukemia cells from CML patients in vitro and K562 xenografts in vivo, can also augment the early ROS production [50]. Withaferin A, which induces apoptosis in HL-60 cells through multiple pathways, also enhances early ROS accumulation leading to loss of mitochondrial membrane potential and cytochrome c release, Bax translocation, caspase activation, and PARP cleavage [51]. It enhanced caspase-8 activity, caspase 3-mediated nuclear cleavage of p65/Rel, which was inhibited by N-acetylcysteine, an antioxidant, suggesting the role of early ROS production in withaferin A-mediated apoptotic signaling. The anticancer molecules, such as betulinic acid, a pentacyclic triterpene, have also been reported to directly activate mitochondria-mediated intrinsic pathway and exhibit antitumor activity [50, 52]. Resveratrol, a phytoalexin found in various food products, induces human promyelocytic leukemia cell differentiation, inhibits cyclooxygenase and hydroperoxidase functions and the development of pre-neoplastic lesions in carcinogen-treated mouse mammary glands as well as tumorigenesis in a mouse skin cancer model [53]. Various other substances isolated from plant material and found to be effective in cancer include: 2-deacetoxytaxinine (from the bark of Himalayan yew, Taxus wallichiana) [54], curcumin (from Curcuma longa) [55], quercetin 3-O-rutinoside (from the fruits of Barringtonia racemosa) [56], 13-epi-sclareol (from the roots of Coleus forskohlii) [57], corchorusin-D (from Corchorus acutangulus) [58], tetranortriterpenoid methyl angolensate (from the root callus extract Soymida febrifuga) [59], oleanonic acid (from Lantana camara) [60], longitriol and longimide (from the leaves of Polyalthia longifolia) [61], 1-hydroxytectoquinone (from Rubia cordifolia) [62], 3-(8′(Z),11′(Z)-pentadecadienyl catechol (from Semecarpus anacardium nut) [63], β-sitosterol (from Asclepias curassavica) [64], sulfonoquinovosyl diacylglyceride (isolated from leaves of Azadirachta indica) and nimbolide (from the leaves and flowers of A. indica) [65], diallyl disulfide (from Allium sativum) [66], arjunic acid (from Terminalia arjuna) [67],
Diets high in fruits and vegetables may reduce the risk of cancers [74–78]. Tomato and tomato-based products have been found to be effective in the stomach, lung and pleural, colorectal, oral/laryngeal/pharyngeal, esophageal, pancreatic, prostate, bladder, breast, cervical and ovarian cancers [79]. Lycopene (LYC) (C40H56; Molar mass, 536.873 g/mol) is a bright red-colored carotenoid pigment found in red fruits and vegetables particularly tomato, carrot, watermelon, guava, etc., (but not in all red fruits, like strawberries, or cherries) and also in some vegetables that are not red, such as parsley and asparagus. The beneficial effects of tomato on health have been attributed to the presence of LYC. LYC is a highly unsaturated, straight-chain hydrocarbon containing 11 conjugated and two non-conjugated double bonds (Figure 1).
\nChemical structures of lycopene isomers.
It is a non-provitamin A carotenoid. The biological significance of carotenoids has been well established and documented. The β-carotene, for example, is converted into retinal, retinoic acid, and apocarotenoids, which plays a very important role in human/animal physiology [80]. LYC is non-provitamin A carotenoid which is not converted to vitamin A. It is a major component found in the serum and other tissues and has been inversely related to cancer and cardiovascular diseases [81]. The molecule acts as an antioxidant and has been reported to have beneficial effects, which can be attributed to its unique chemical structure [82]. LYC can modulate the intercellular gap junction communication, hormonal and immune system, and metabolic pathways.
\nLYC exists predominantly in trans-configuration, the most thermodynamically stable form, and as a polyene, it undergoes cis-trans isomerization induced by light, thermal energy or chemical reactions. In human plasma, LYC is an isomeric mixture containing 50% of total LYC as cis isomers. All-trans, 5-cis, 9-cis, 13-cis, and 15-cis are most commonly identified isomeric forms of LYC. LYC is poorly absorbed when ingested in its natural trans-form found in tomatoes. Heat processing of tomatoes and tomato products increases the bioavailability of LYC by inducing isomerization of LYC to the cis form [83]. LYC, which when oxidized with potassium permanganate and by atmospheric oxygen catalyzed by a metalloporphyrin, is converted into apo-lycopenals and apo-lycopenones [84]. In addition, a number of other apo-lycopenals have been suggested in fruits, vegetables, and human plasma [85–87].
\nCarotenoid-rich foods have been associated with reduced risk of cancer, such as the prostate and other cancers by various mechanisms [81, 88–95]. The enhanced cytotoxic and apoptosis inducing the activity of LYC has been recorded in different cancer cell lines [96]. The influence of LYC and its oxidation products on the levels of intracellular ROS in three different cell lines has been studied, and in all the cases, the oxidation products increased the ROS levels than the LYC- and control-treated cells. In MCF-7 cells, ROS in control- and LYC-treated groups was lower by 16.3 and 15.5% than in oxidation product treated cells [96].
\nA number of mechanisms of action have been proposed to explain the anticarcinogenic action of LYC. These include: (i) the inhibition of cancer cell proliferation and induction of differentiation (of cancer cells) by modulating the expression of cell cycle regulatory proteins, (ii) modulation of the IGF-1/IGFBP-3 system, (iii) inhibition of oxidative DNA damage, (iv) modulation of redox signaling, (v) upregulation of gap-junctional gene connexin 43 (Cx43) and increased gap junctional intercellular communication, (vi) inhibition of 5-lipoxygenase, (vii) modulation of carcinogenic metabolizing enzymes, (viii) modulation of immune function, (ix) modulation of IL-6 and androgen, (x) inhibition of IL-6 and androgen, (xi) inhibition of 5-lipoxygenase, (xii) modulation of carcinogen metabolizing enzymes and (xiii) modulation of immune function [97], (xiv) reduction of oxidative stress by modulating ROS-producing enzymes (CYP-P450 enzymes, NADPH oxidase, iNOS, COX-2 and 5-LOX), (xv) inducing antioxidant/detoxifying phase II enzymes (also chemical interaction with radioactive materials), NQO1 and GST [98], (xvi) regulation of nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) system [99], and (xvii) inactivation of growth factor (PDGF, VEGF and IGF)-induced PI3K/AKT/PKB and Ras/RAF/MAPK signaling pathways [100] (Figure 2)
\nMechanisms of cancer chemoprevention by lycopene.
The beneficial effects of LYC in prostate cancer (PC) have been extensively reported. A significant inverse correlation between PC and plasma LYC concentration [odds ratio (OR) = 0.17, P-trend = 0.005] has been found between the highest and lowest quintiles of intake [101]. In several experimental studies, LYC has been suggested to suppress PC in vitro and in vivo [102, 103]. It was found to down-regulate the expression of protein kinase B (AKT2) and up-regulate miR-let-7f-1 expression in PC3 cells. Reintroduction of miR-let-7f-1 into PC3 cells was able to inhibit cell proliferation and induce apoptosis. Further research has shown that up-regulation of miR-let-7f-1-targeted AKT2 and AKT2 in PC3 cells can alleviate the effects induced by miR-let-7f-1 [104]. In a recent study published by Tan et al. [105], mice fed semi-purified diets containing 10% tomato powder or 0.25% LYC beadlets up to 18 weeks had higher serum concentrations of total, 5-cis, other cis and all-trans as compared with control in β-carotene 9′,10′-oxygenase (BCO2) +/+ mice. The incidence of PC was lower in animals fed with tomato and LYC when compared with control group. The ability of LYC and tomato to inhibit prostate carcinogenesis was significantly attenuated by loss of BCO2 (P-interaction = 0.0004 and 0.0383, respectively), although the BCO2 genotype did not significantly alter the PC outcome in mice fed with the control AIN-93G diet alone. In another study, the treatment with LYC or metabolite with apo-10-lycopenal increased the BCO2 expression and decreased cell proliferation in androgen-sensitive cell lines, but did not alter BCO2 expression or cell growth in LYC androgen-resistant cells. In particular, restoration of BCO2 expression in PC cells prevented cell proliferation and colony formation independent of LYC exposure [106]. Yang et al. [107] reported that a low or high dose of LYC (4 and 16 mg/kg) and a single β-carotene (16 mg/kg) twice weekly for 7 weeks strongly inhibited the tumor growth, as evidenced by the decrease in tumor volume and tumor weight in thimeric nude mice implanted subcutaneously with human androgen-independent prostate carcinoma PC-3 cells. At high dose level, LYC and β-carotene significantly reduced the expression of PCNA (proliferating cellular nuclear antigen) in tumor tissues and increased insulin-like growth factor-binding protein-3 levels in the plasma. In addition, LYC supplementation at high dose level significantly reduced vascular endothelial growth factor (VEGF) in the plasma. Tang et al. [94] also showed that supplemental LYC inhibited the growth of DU145, a human prostate tumor cell line, transplanted into BALB/c nude mice.
\nSeveral studies supporting the relationship between consumption of tomato products and a reduced incidence of PC have come from the Health Professionals Follow-Up Study. In a randomized two-arm clinical trial, patients who have diagnosed PC and scheduled to undergo radical prostatectomy were randomly assigned to either 30 mg of oral LYC supplementation or no intervention for 3 weeks prior to surgery. The study reported that the plasma prostate-specific antigen (PSA) level decreased by 18% in the intervention group, while it increased by 14% in the control group over the study period. In the intwervention group, 11 of 15 patients (73%) had no involvement of surgical margins and/or extraprostatic tissues with cancer, compared to 2 of 11 patients (18%) in the control group. Twelve of 15 patients (80%) in the LYC group had tumors that measured 4 cc or less, compared to 5 of 11 (45%) in the control group [108]. In the same study, Kucuk et al. noted that the expression of Cx43 in the malignant part of the prostate glands was higher in LYC group than the control group. Prostatic tissue LYC levels were 47% higher in the intervention group compared to control group [108]. Phase II randomized clinical trial of 15 mg of LYC supplementation twice a day for 3 days before radical prostatectomy showed a decrease in plasma IGF-I levels, but no significant change in Bax and Bcl-2 [109]. Recently, Paur et al. [110] showed that post hoc, exploratory analyses within intermediate risk patients based on tumor classification and grade and Gleason post-surgery revealed that median PSA decreased in the tomato group as compared to controls (−2.9 and +6.5%). Separate post hoc analyses showed that the median PSA values reduced by 1% in patients with the highest increase in plasma LYC, selenium and C20:5 n-3 fatty acid, compared with the 8.5% increase in patients with the lowest increase in LYC, selenium, and C20:5 n-3 fatty acid. In addition, PSA decreased in patients with the highest increase in LYC (p = 0.009). In addition, it was showed that neither pre-diagnosis nor post-diagnosis dietary LYC intake was associated with PC-specific mortality (PCSM) (fourth and first quartile HR = 1.00, 95% GA 0.78–1.28, HR = 1.22, 95% GA 0.91–1.64, respectively). Also, neither pre-diagnosis nor post-diagnosis consumption of tomato products was associated with PCSM. Among subjects with high-risk cancers (T3-T4 or Gleason score 8–10 or nodal involvement) consistently reporting LYC intake ≥median on both postdiagnosis surveys was associated with lower PCSM (HR = 0.41, 95% GA 0.17–0.99, based on ten PCSM cases consistently ≥median intake compared to consistently reporting intake <median [111].
\nIn vitro and in vivo studies suggest that intake of LYC-containing foods may reduce breast cancer risk. Assar et al. [112] have recently reported that LYC inhibits prostate as well as breast cancer cell growth at physiologically relevant concentrations ≥1.25 μM. Similar concentrations also caused a 30–40% reduction in IκB phosphorylation (which regulates the activity of NF-κB [113] as determined by Western blot analysis. However, immunofluorescence staining of LYC-treated cells showed a significant suppression of NF-κB p65 subunit nuclear translocation (≥25%) caused by TNF. In another in vitro study reported by Gloria et al. [114], a significant decrease in the number of viable breast cancer cells treated with LYC and beta-carotene carotenoids were observed. Carotenoids promoted cell cycle arrest and then decreased cell viability in the majority of cell lines after 96 h from the controls. In addition, when cells were treated with carotenoids, an increase in apoptosis was observed in cell lines. Cui et al. [115] reported that LYC intake was inversely associated with estrogen and progesterone receptor positive breast cancer risk in postmenopausal women (n = 84,805), averaging 7.6 years (RR = 0.85 for high quartile of intake as compared with the lowest quartile of intake, P-trend = 0.064). In an animal study, the incidence of breast cancer was found to be inhibited by LYC (70%), genistein (60%) and their combination (40%). Tumor weight was reduced by 48, 61 and 67% with LYC, genistein and LYC + genistein, respectively, and the mean tumor volume decreased by 18, 35, and 65%, respectively. Administration of the combination of LYC and genistein suppressed breast cancer development and was associated with a decrease in malondialdehyde (MDA), 8-isoprostane and 8-OHDG levels, and increase in serum LYC and genistein. Animals treated with DMBA developed breast cancer associated with increased expression of Bcl-2 in breast tissues and decreased expression of Bax, caspase-3, and caspase-9. The combination of genistein and LYC was more effective than either agent alone to inhibit DMBA-induced breast tumors and to modulate the expression of apoptosis-associated proteins [116]. Recently, in a randomized, placebo-controlled, double-blind, cross-over study, Voskuil et al. [117] found that tomato extract supplementation (30 mg/day LYC) for 2 months reduced free insulin-like growth factor-I (IGF-I) in premenopausal women with a high risk of breast cancer (n = 36) I) by 7.0%. Al-Malki et al. [118] demonstrated that combined treatment of LYC and tocopherol (LYC-Toco) caused a reduction in MDA and nitric oxide (NO) in serum and breast tissues in LYC-Toco group than the LYC alone group. Superoxide dismutase, catalase, and glutathione peroxidase activities were significantly higher when compared to rats treated with LYC alone. Serum alanine transaminase, aspartate aminotransferase, total bilirubin and malondialdehyde, which increased in the group of rats treated with diethylnitrosamine (DEN), and hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and glutathione, which decreased in the cancerous group, improved in LYC-treated animals [119]. LYC also caused a reversal and reduced NF-κB and cyclooxygenase-2, consequently increasing Nrf2/HO-1 expression and inhibition of inflammatory cascade, thereby activating the antioxidant signaling. LYC also reduced increases in phosphorylated mammalian targets for phosphorylated rapamycin (p-mTOR), phosphorylated p70 ribosomal protein S6 kinase 1, phosphorylated 4E-binding protein 1, and protein kinase B.
\nStudies have also reported a positive correlation between LYC or tomato product consumption and gastric and colorectal cancers [120, 121]. Although there has been a series of epidemiological studies investigating the relationship between LYC or LYC-rich food and serum/plasma LYC concentration and colorectal cancer risk, the results of these studies have not been consistent [79, 122]. Teodoro et al. [123] have demonstrated a significant reduction in the number of viable cells in human colon adenocarcinoma cells (HT-29), human colon carcinoma cells (T-84), and breast cancer cell line (MCF-7) after 48 h of treatment with LYC. LYC stimulated cell cycle arrest followed by reduced cell viability in the majority of cell lines after 96 h as compared to controls. In addition, when cells were treated with LYC, an increase in apoptosis was observed in four cell lines (T-84, HT-29, MCF-7, and DU145). LYC has also been reported to inhibit cell proliferation in human colon cancer HT-29 cells with IC50 value of 10 μM. LYC treatment also suppressed Akt activation and non-phosphorylated β-catenin protein levels in human colon cancer cells. In addition, LYC significantly increased the nuclear cyclin-dependent kinase inhibitor p27(kip) abundance and inhibited the phosphorylation of retinoblastoma tumor suppressor protein in human colon cancer cells [124]. In another study, it was shown that inhibition of cell growth by tomato digestate was dose dependent and resulted from cell cycle arrest at G0/G1 and G2/M phase and progression by apoptosis induction. Down-regulation of Cyclin D1, Bcl-2, and Bcl-x1 expression has also been observed [125]. In a study conducted by our research group [126], we showed that 5% of the tomato powder added to the diet reduced the aberrant crypt foci (ACF) ratio and also reduced adenocarcinoma development and azoxymethane (AOM)-induced colorectal cancer formation in rats. In addition, the addition of tomato powder indicated that it exhibits chemopreventive activity by regulating Nrf2/HO-1 signaling pathway in colorectal tissue while inhibiting cyclooxygenase-2 (COX-2) expression and inducing apoptosis via the NF-κB pathway. Dias et al. [127] reported that treatment with LYC, synbiotics or a combination thereof significantly increased apoptosis, decreased PCNA and p53 labeling indices, and classical ACF and mucin-negative ACF development. In addition, a lower genotoxicity of fecal water was also detected in groups treated with the chemopreventive agents. The additive/synergistic effect of combined treatment with LYC/synbiotics was observed only for the fecal water genotoxicity and mucin-negative ACF parameters. In a study in a mouse xenograft model, Tang et al. [128] reported that LYC suppressed the nuclear expression of PCNA and β-catenin proteins in tumor tissues. LYC consumption may also increase the nuclear levels of the E-cadherin adherent molecule and the cell cycle inhibitor p21 (CIP1/WAF1) protein. The inhibitory effects of LYC were associated with the suppression of COX-2, PGE (2) and phosphorylated ERK1/2 proteins. In addition, the inhibitory effects of LYC were inversely correlated with plasma levels of matrix metalloproteinase 9 (MMP-9) in tumor-bearing mice.
\nIn a randomized, placebo-controlled, double-blind crossover study, the tomato-based LYC supplementation (Lyc-o-Mato®, 30 mg/day LYC) for 8 weeks has been reported to increase serum insulin-like growth factor binding protein-1 (IGFBP-1) concentration in men and women with high risk for colorectal cancer [129]. The group also reported that the serum IGFPB-2 concentration in men and women increased by 8.2 and 7.8%, respectively. In a double-blind, randomized, placebo-controlled trial, Walfisch et al. [130], a reduction of 25% in plasma IGF-I concentration was reported in 30 patients waiting for colectomy surgery, supplemented with Lyc-o-Mato®. In the same study, a 24% reduction in IGF-I/IGFBP-3 ratio was also observed. In another study, 20 healthy individuals participated in a double-blind crossover dietary intervention and consumed a tomato juice drink (250 ml Lyc-o-Mato® beverage, 5.7 mg LYC, 3.7 mg phytoene, 2.7 mg phytoplankton, 1.8 mg α-tocopherol) and a 26-day wash between each placebo drink [131] for 26 days each. The blood plasma levels of IGF-I were found to be inversely correlated with the consumption of LYC. In yet another study, 20 healthy subjects participated in a double-blind crossover dietary intervention and consumed a tomato juice beverage (250 ml of Lyc-o-Mato® drink) and a 26-day wash between each placebo drink, the plasma IGF-I levels were inversely correlated with the intake of LYC [131].
\nLYC has also been reported to inhibit Helicobacter pylori-induced increases in ROS, 8-OH-dG, and apoptosis by increasing Bax and decreasing Bcl-2 expression as well as PARP-1 cleavage, changes in cell cycle distribution, double-stranded DNA breaks, activation of ataxia-telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR)-mediated DNA damage response in gastric epithelial AGS cells [132]. The administration of LYC (50, 100 and 150 mg/kg body weight) in gastric carcinoma-induced rats up-regulated the redox status and immune activities and was useful in reducing the gastric cancer risk [133].
\nThe frequent consumption of tomatoes and tomato-based products has been suggested to lower the risk of other cancers, such as the liver, renal and ovarian cancers. LYC can block the growth on human Hep3B hepatoma cells in a dose-dependent manner and at the same time has been shown to inhibit metastasis in SK-Hep 1 human hepatoma cell line [134, 135]. In a study conducted by our research group, we reported a decrease in serum alanine transaminase, aspartate aminotransferase, total bilirubin and malondialdehyde by LYC in the diethylnitrosamine (DEN)-treated animals. LYC increased the hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and glutathione and reduced the NF-κB/cyclooxygenase-2. The Nrf2/HO-1 expression increased, and the inflammatory cascade inhibited by LYC, suggesting an activation of the antioxidant signaling by LYC. In this study, LYC reduced the increases in phosphorylated mammalian targets of phosphorylated rapamycin (p-mTOR), phosphorylated p70 ribosomal protein S6 kinase 1, phosphorylated 4E binding protein 1, and protein kinase B [119]. In another study on DEN-induced hepatocarcinogenesis in rats, LYC was reported to be effective against preneoplastic foci in the liver by decreasing the size of the liver; whereas LYC administration in another animal study did not reduce the risk of spontaneous liver cancer [136, 137]. The LYC-added tomato paste has been reported to be protective against oxidative stress induced by N-nitrosodiethylamine (NDEA) in rats. It decreases the microsomal lipid peroxidation in the liver and significantly reduced plasma protein carbonyl levels [138]. LYC supplementation also prevents liver-specific carcinogenic DEN-induced of hepatic preneoplastic foci and macroscopic nodules in rat hepatic glutathione S-transferase placental-form positive foci in rats that developed spontaneous liver tumors and ameliorated DEN-initiated, HFD (high-fat diet)-promoted precancerous lesions [139, 140]. It was effective in decreasing NASH-promoted, DEN-initiated hepatocarcinogenesis in rats [136]. Apo-10′-lycopenoic acid, a LYC metabolite produced by β-carotene-9′,10′-oxygenase (BCO2) inhibited hepatic inflammation and liver inflammation induced by carcinogen-initiated high-fat diets [98, 141] showed that LYC supplementation (100 mg/kg diet) for 24 weeks decreased hepatic proinflammatory signal (phosphorylation of NK-κB p65 and STAT3, IL6 protein) and inflammatory foci in wild-type mice. In contrast, the protective effects of LYC in BCO2-KO were related to reduce hepatic endoplasmic reticulum stress-mediated unfolded protein response, the ER(UPR), through decreasing ER(UPR)-mediated protein kinase RNA-activated like kinase-eukaryotic initiation factor 2α activation, and inositol-requiring 1α-X-box-binding protein 1 signaling. LYC treatment in BCO2-KO mice inhibited carcinogenic signals, including Met mRNA, β-catenin protein and mTOR complex 1 activation associated with increased liver microRNA (miR)-199a/b and miR214 levels [141]. The connection between LYC and aflatoxin B1 (AFB1) initiated HCC has also been examined [142], and in recent studies [143], the hepatocarcinogenesis pathway has been linked to the activation of the oxidative stress-inflammatory pathway in rat liver.
\nPrevious research has shown that micronutrients consumed through diet or dietary supplementation, including vitamin E and carotenoids, can inhibit oxidative DNA damage, mutagenesis and tumor growth [144, 145]. However, many studies have shown that there is no significant association between RCC and antioxidant micronutrient intake [146], while others suggest supportive evidence that some micronutrients may have a protective effect [147]. Increased uptake of LYC in postmenopausal women in the Women’s Health Initiative (WHI) was inversely associated with RCC risk (p = 0.015); compared with the lowest quartile of LYC intake, the highest quartile of intake was associated with a 39% lower risk for RCC (hazard ratio, 0.61, 95% confidence interval, 0.39–0.97) when compared with the lowest quartile of LYC intake [145]. It was also reported that no other micronutrient was significantly associated with RCC risk [145]. Another case-control study reported that the intake of vegetables was associated with a reduction in the risk of RCC (OR 0.5; 95% CI 0.3, 0.7; P trend = 0.002) [148]). In the same study, it was reported that both β-cryptoxanthin and LYC were associated with reduced risks, but when both were included in a mutually adjusted backward stepwise regression model, only β-cryptoxanthin remained significant (OR 0.5; 95% CI 0.3, 0.8). When other micronutrients and fiber types were investigated together, only vegetable fiber and β-cryptoxanthin showed significant trends. They also reported that these findings are stronger for people over 65 years of age. Additionally, among nonsmokers, low intake of cruciferous vegetables and fruit fiber was also associated with increased risk of RCC (P interaction = 0.03); similar reverse relationships were found for β-cryptoxanthin, LYC and vitamin C [148]. LYC has also been found to decrease the tumor presence and the average number of renal carcinomas in a small animal model (rat) for studying renal cell carcinoma (RCC) [149]. In the LYC group, the tumor counts decreased and as the LYC supplement increased from 0 to 200, the numbers tended to decrease linearly. Control rats fed only on a basal diet had a greater length of tumors (23.98 mm) than those fed to LYC supplementation groups (12.90 and 2.90 mm) (11.07 mm). In addition, when LYC increased from 0 to 200 mg/kg, tumor length decreased. It tended to decrease linearly. All tumors showed strong staining with antibodies to mTOR, phospho-S6, and EGFR.
\nLYC supplementation has been reported to exhibit a non-significant trend after administration of N-butyl-N-(4-hydroxybutyl) nitrosamine to reduce the number of bladder transitional cell carcinomas in rats [150]. In a case-control study involving 569 bladder cancer cases and 3123 controls, the relative risk for bladder cancer was 1.08, which compared the highest and lowest rates of LYC uptake [151]. However, in a cohort study, serum LYC levels in bladder cancer cases were found to be lower than those of compatible controls [152]. In another case-control study with 84 cases and 173 controls, OR for bladder cancer was 0.94 (95% CI 0.89–0.99) in the highest quartile of plasma LYC intake when compared to lowest after controlling for age, sex, education, and pack-years of smoking [153].
\nMany studies have shown that smokers and lung cancer patients tend to be lower plasma concentrations of b-carotene, retinol, LYC, b-cryptoxanthin and a-tocopherol [154]. Graham et al. [155] have treated LYC solutions with human plasma and isolated LDL with cigarette smoke and observed the depletion of all(E)-chylopen, 5 (Z)-chylonopen and beta-carotene. Depletion of all-(E)-lycopenin (15.0 ± 11.0%, n = 10) was greater than 5 (Z)-lycopenin (10.4 ± 9.6%) or beta-carotene (12.4 ± 10.5%) in plasma. LDL was found to be more sensitive to both all(E)- and 5 (Z)-clycopenia than beta-carotene (20.8 ± 11.8, 15.4 ± 11.5 and 11.5 ± 12.5%, n = 3). It was also reported that smoke exposure reduced the concentrations of LYC in plasma and lung tissue of LYC supplemented ferrets, which was consistent with the National Health and Nutrition Examination survey III finding that smokers had lower serum levels of LYC compared to nonsmokers [156]. In one study, the concentration of LYC in lungs was 1.2 μmol/kg lung tissue in ferrets fortified with LYC at a dose of 60 mg/day, and this did not cause a harmful effect, instead it prevented the induction of lung squamous metaplasia and cell proliferation induced by smoke exposure [157]. On the other hand, intake of tomato or tomato products including LYC has been associated with a lower risk of lung cancer [158]. In cell culture, LYC has been shown to inhibit the nitration of proteins and DNA strand breakage caused by peroxynitrite treatment of hamster lung fibroblasts [159]. Apo-100-lycopenoic acid has been reported to inhibit the growth of the normal human bronchial epithelial cells, BEAS-2B immortalized normal bronchial epithelial cells, and A549 non-small cell lung cancer cells [158]. LYC dissolved in drinking water at a dose of 50 ppm significantly reduced diethylnitrosamine (DEH), methylnitrosourea (MNU), and dimethylhydrazine (DMD)-induced lung adenomas along with carcinomas in male mice [160]. The inhibitory effect of apo-100-lycopenoic acid was associated with decreased cyclin E, inhibition of cell cycle progression and an increase in cell cycle regulator p21 and p27 protein levels. In addition, apo-100-lycopenoic acid trans-activated the retinoic acid receptor β (RARβ) promoter and initiated the expression of RARβ. In another animal study, the incidence of lung adenomas and carcinomas in male mice receiving 50 ppm LYC in addition to diethylnitrosamine (DEN), N-methyl-N-(MNU) and 1,2-dimethylhydrazine (DMH) was lower than the incidence seen in non-LYC recipients (18.8 versus 75.0%) [161].
\nSome plant and plant-based products and their active ingredients exhibit significant antitumor properties. They may act by blocking the cell cycle checkpoints (paclitaxel) and specific enzymes, such as the S-phase specific topoisomerase-I (camptothecins) and S and G2 phase-specific topoisomerase-II (etoposide), and by preventing the microtubule polymerization (vinblastine), as well as by various other mechanisms. Diallyl disulfide, limonoids, azadirachtin, pentacyclic triterpenediol, theaflavins, curcumin, lupeol, and AECHL-1 [162–169], for example, modulate the p53-regulated pathways. Bromelain, theaflavin, thearubigin, curcumin, E-piplartine (trans-piplartine), 3β-hydroxylup-20(29)-ene-27,28-dioic acid, withanolide D, withaferin A [70, 170–176] affect MAPK-regulated pathways. The other pathways include death receptors (example, theaflavins [177] and ROS-mediated pathways (isointermedeol, mahanine, chlorogenic acid, withaferin A [50, 51, 178]. The β-sitosterol, which has a significant anticancer activity against colon cancer, acts by scavenging ROS and suppressing the expression of PCNA [62]. Sesquiterpene isointermedeol (ISO), which is a major constituent of Cymbopogon flexuosus (lemon grass) and inhibitor of proliferation of human leukaemia HL-60 cells, also induces ROS production with the concomitant loss of mitochondrial membrane potential, DNA laddering, and apoptotic body formation.
\nLYC, which is a highly unsaturated, straight-chain hydrocarbon, is reported to be beneficial in cancers, especially the prostate cancer. It can reduce oxidative stress by modulating ROS-producing enzymes (CYP-P450 enzymes, NADPH oxidase, iNOS, COX-2, and 5-LOX) and inducing antioxidant/detoxifying phase II enzymes [98]. These phase II enzymes are regulated by the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) system. The Nrf2/HO-1 signaling is suggested to be an important primary target for chemoprevention (cisplatin-induced nephrotoxicity) by LYC. LYC can also decrease inflammation by inhibiting NF-κB [99]. It can inhibit the proliferation and induction of differentiation of cancer cells by modulating the expression of cell cycle regulatory proteins, modulating the IGF-1/IGFBP-3 system and other mechanisms including the prevention of oxidative DNA damage and modulation of the immune function, as well as the inactivation of growth factor (PDGF, VEGF, and IGF) induced PI3K/AKT/PKB and Ras/RAF/MAPK signaling pathways [100].
\nOverall, the research articles reviewed in this chapter provide convincing evidence suggesting a role for LYC in cancer, particularly in prostate cancer. LYC may act by a variety of mechanisms, some of which could be linked to the antioxidant activity of this non-pro-vitamin-A carotenoid. Lycopene supplementation could be a potential candidate for future clinical trials in prostate cancer and other cancers both as a preventive and therapeutic agent and in combination with other therapies. This phytochemical offers great promise in integrative oncology and warrants further clinical evaluation with careful attention to individualized dose escalation until an effective and safe dose is found.
\nThis work was supported by the Turkish Academy of Sciences (KS).
\nThis chapter will review our current state of the art knowledge about bulgecins, natural inhibitors of lytic transgylcosylase cell wall enzymes, and their activity as β-lactam enhancers to inhibit growth of P. aeruginosa. Current known resistance mechanisms targeting β-lactams in P. aeruginosa be reviewed, followed by an introduction to the lytic transglycosylases of P. aeruginosa. The use of bulgecins as adjunctive agents with β-lactams will be described as well as the synthesis of Bulgecin A, the most active of these compounds.
P. aeruginosa has intrinsically higher minimum inhibitory concentrations (MICs) against anti-pseudomonal β-lactams when compared to Enterobacteriaceae, even in the absence of specific resistance determinants. For example, typical MICs for the anti-pseudomonal cephalosporin, ceftazidime, for Escherichia coliare 0.06–0.125 mg/L whereas for P. aeruginosa isolates, MICs are in the range of 1–2 mg/L. In the main, when P. aeruginosa is resistant to β-lactams, specific mechanisms are at play. These include downregulation of outer membrane porins, expression of intrinsic efflux mechanisms, acquisition of β-lactamase enzymes including carbapenamases such as IMP (“imipenemase”), VIM (“Verona imipenemase”) and KPC (“Klebsiella pneumoniae carbapenemase”), hyperproduction of chromosomal β-lactamases (“AmpCs or
Resistance determinant | Antibiotics affected | |
---|---|---|
Pseudomonas aeruginosa | OprD loss | Carbapenems, some cephalosporins, penicillins |
Efflux pumps (e.g., MexA-B/OprM) | Meropenem, some cephalosporins, penicillins | |
Chromosomal Amp C of P. aeruginosa | Anti P. aeruginosa penicillins, anti P. aeruginosa cephalosporins except ceftolozane | |
Acquired ESBLs (TEM, SHV,OXA, GES, VEB, CTX-M, PER) | anti P. aeruginosa cephalosporins except ceftolozane, cefepime | |
Acquired carbapenemases (KPC, OXA, metallo-β-lactamases like NDM, VIM, IMP, SPM types) | anti P. aeruginosa pencillins, cephalosporins and carbapenems |
β-Lactam resistance determinants in P. aeruginosa.
OprD, outer membrane porin D; Mex-multidrug efflux; TEM, class A β-lactamase of E. coli, named for patient in which it was discovered; SHV, sulfhydryl variant of TEM; OXA, oxacillinase; GES, German extended spectrum β-lactamase; VEB, Verona extended spectrum; CTX-M, cefotaximase-München; PER, plasmidic extended spectrum β-lactamase; NDM, New Delhi metallo-β-lactamase; SPM, Sao Paolo metallo-β-lactamase.
Currently, in the clinical microbiology laboratory, susceptibilities are reported to particular antibiotics depending on the specific sample submitted, e.g., urine, blood, sterile body fluids (pleural, joint, cerebrospinal fluid). At least initially, genotypic testing to determine the presence of specific antibiotic resistance determinants is not performed, and it is left to the clinical infectious diseases expert to reason out the most likely resistance mechanisms based on susceptibility patterns, and to select the most appropriate antibiotic(s) for treatment.
The structure, function and regulation of P. aeruginosa porins is complex and has been recently reviewed [2]. Porins are involved in structural and signaling tasks in P. aeruginosa, as well as passage of nutrients. The Opr D family of porins is the largest and is subdivided into two groups OccD and OccK. These porins are each regulated through their own sigma factors. Porin loss can be related to formation of OprD containing outer membrane vesicles that are also found in high concentrations in biofilms. Resistance to carbapenems in biofilms may be related to this. Mutations in P. aeruginosa that cause oprD (occD1) to not be expressed are linked to imipenem resistance. Other occD1 mutations that do not effect transcription also lead to carbapenem resistance [3, 4]. OprD mutations or loss is often associated with overexpression of efflux pumps (see below) leading to high level resistance to carbapenems, other β-lactams and other classes of antibiotics such as aminoglycosides and fluoroquinolones [5].
In the clinical setting, OprD porin loss is often associated with a resistance phenotype in which one observes resistance to carbapenems including imipenem, but in vitro susceptibility to anti-pseudomonal pencillins and cephalosporins. In combination with other resistance mechanisms, such as over-expression of the chromosomal PDC enzymes, or presence of other acquired cephalosporinases such as TEM, SHV and OXA β-lactamases, higher level carbapenem resistance is observed as well as resistance to other classes of β-lactam antibiotics.
As with porins, P. aeruginosa possesses a large variety of efflux pumps that perform different roles in the bacteria, but mainly function to extrude harmful substances from the cell. These pumps have been reviewed in [6]. Pumps of importance in carbapenem and other antibiotic efflux are in the resistance nodulation or RND type family and include the MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY-OprM multidrug efflux pump systems [7]. Increased expression of these pumps leads to high level carbapenem resistance, often in association with OprD loss or modification. Notably imipenem is not a substrate of the multidrug efflux pumps of P. aeruginosa while meropenem is [7]. In the clinical setting, if one notes resistance to meropenem and other β-lactams, except for imipenem, then an efflux mechanism is at play. If resistance is noted to both meropenem and imipenem, but not to other β-lactams, OprD loss or modification is responsible. With resistance to carbapenems as well as other β-lactams, multiple resistance mechanisms can be at play including efflux, intrinsic and acquired β-lactamases and decreased permeability (porin loss).
As in other organisms, of which Enterobacter cloacae is the most well-known example, P. aeruginosa possesses a chromosomal AmpC β-lactamase also called PDC. Chromosomal β-lactamases likely play a role in cell wall maintenance, as well as degradation of β-lactam antibiotics. As characterized in E. cloacae [8], the AmpC cephalosporinases are under the regulation of ampR, a LysR type regulatory system [9]. Under normal circumstances, there is low level constitutive expression of the AmpC protein. Upon exposure to β-lactam antibiotics, muramyl pentapeptides are released that displace a repressor protein encoded by ampR from the promoter of AmpC. This leads to increased expression of AmpC cephalosporinase. The increased expression of AmpC can occur with exposure to cephamycins like cefoxitin for example. Increased expression of AmpC in E. cloacae occurs via a pathway involving NagZ, a N-acetyl-β-D-glucosamindase, or independent of NagZ [8]. The muramyl pentapeptides are also degraded by a cytosolic amidase, Amp D. This leads to re-association of the repressor to the promoter and resumption of normal levels of Amp C expression. There are also insertion sequence mutations in AmpR that can lead to increased expression of AmpC, as well as mutations in AmpD amidases that reduce degradation of muramyl pentapeptides. The regulation of Amp Cs differs somewhat in P. aeruginosa, involving 2 pathways that include the lytic transglycosylases Slt, SltB1, MltB and MltF, and PBP 4 in the generation of muramyl peptides [10]. Mutations in PBP4 are associated with higher levels of AmpC expression. Finally there are specific AmpC mutations that can lead to a carbapenemase phenotype in these enzymes, although the significance of this in terms of clinically relevant carbapenem resistance is unclear [11].
β-lactamases from all four Ambler classes have been described in P. aeruginosa, including Class A extended spectrum β-lactamases (ESBLs) of the TEM, SHV, CTX-M, GES, PER and VEB types; Class A carbapenemases such as KPC variants; metallo-β-lactamases such as the VIM, IMP, NDM and SPM B1 di-Zn2+ enzymes: and OXA carbapenemases [9, 12]. Weak imipenemases in the so-called Class C AmpCs have already been discussed above. In combination with OprD loss and/or upregulation of MEX efflux pumps, high level carbapenem resistance can be seen in P. aeruginosa due to acquired β-lactamases. Traditional class A β-lactamase inhibitors such as clavulanic acid, sulbactam and tazobactam have in vitro activity versus the Class A ESBLs but not against other β-lactamases, e.g., the anti-pseudomonal combination ceftolozane-tazobactam is not effective against KPC, metallo-b-lactamases, or OXA enzymes [1]. New β-lactam-β-lactamase inhibitor combinations such as ceftazidime-avibactam and meropenem-vaborbactam will be active against isolates with KPC enzymes, and Class C β-lactamases, as long as they lack other resistance mechanisms that increase the β-lactam MIC beyond what is caused by the β-lactamase enzyme [13, 14].
PBPs of P. aeruginosa have high affinities for so called anti-pseudomonal β-lactams namely piperacillin, ticarcillin, ceftazidime, cefepime, ceftolozane, meropenem, imipenem, doripenem and aztreonam [1]. PBP 3 is the most important target of inhibition as it is essential for growth of the bacteria [15]. PBP3 is the primary target for ceftazidime whereas PBP2 is the target of carbapenems. Mutations in PBPs have not been described in P. aeruginosa leading to β-lactam resistance. The interactions of specific PBPs with specific lytic transglycosylases in the maintenance of cell wall will be further discussed below.
Given that 15–33% of P. aeruginosa isolates are multidrug resistant (have at least one resistance mechanism) [16, 17] and that resistance is associated with up to fivefold greater mortality [18, 19], choosing the right antibiotic combinations have a tremendous impact on patient outcomes. Advances in the rapid diagnosis of P. aeruginosa, and use of both rapid phenotypic tests such as CARBA NP [20] or rapid molecular diagnostics to identify specific ESBL and carbapenemase enzymes, have enhanced the clinician’s ability to get patients on the right therapy sooner. Identification of patient risk factors, including prior antibiotic exposure, and knowledge of local trends in resistance patterns are useful in selection of empiric antibiotics, until antimicrobial susceptibilities and genotypic results are available for guidance. Carbapenems (meropenem or imipenem) and anti-pseudomonal cephalosporins in combination with colistin, an aminoglycoside or fosfomycin, versus ceftolozane/tazobactam or meropenem/vaborbactam or ceftazidime/avibactam are all good empiric choices for critically ill patients [16], provided multidrug resistance is not present. However, clearly more therapeutic options are needed for infections with extensively drug resistant and pan-resistant P. aeruginosa. Lytic transglycosylases represent a new target for bacterial inhibition.
Recently, lytic transglycosylases of P. aeruginosa have been extensively characterized [21, 22, 23, 24, 25, 26, 27]. These cell wall proteins are found in many other pathogenic bacteria and are classified according to amino acid sequence and function [28]. To date there are 11 P. aeruginosa lytic transglycosylases that have been described. Their functions range from cell division to aiding in the insertion of secretion systems and two component regulatory systems. They are attractive drug targets to enhance the activity of our most commonly used and safest antibiotics, the β-lactam class (penicillins, cephalosporins, carbapenems and monobactams).
Lts in general catalyze a cleavage reaction that breaks the glycosidic bond between the peptidoglycan building blocks, MurNAc and GlcNAc (Figure 1).
Lt reaction in cell wall remodeling in Pseudomonas aeruginosa. When the transpeptidase (crosslinking function) of a PBP is inhibited by a β-lactam, the tranglycosylase function of the PBP continues to produce strands of uncrosslinked peptidoglycan (PG). The soluble Lt in the periplasm of Gram negative bacteria initiates recycling and cleavage of PG via endolytic (within strand) reaction. Once this first cleavage reaction occurs, the 1,6-anhydroMurNAC-GlcNAC containing fragments are cleaved and released. In P. aeruginosa, these 1,6-anhydromuramylpeptide fragments affect regulation of Amp C β-lactamase production. TP designates tetrapeptide.
This reaction does not involve a water molecule but rather, an active site Glu or Asp residue functions as a general acid, donating a proton to the oxygen in the β-1,4 glycosidic linkage. Then the deprotonated active site residue acts a general base as a nucleophile to break the glycosidic bond. The result is a 1,6-anhydroMurNAc containing final peptide product. This unique cap on the muramyl peptide is a signal and a way for the cell wall peptidoglycan cleavage products to be trafficked for recycling [26]. The reaction shown in Figure 1 is within the strand or “endolytic”. Some Lts also catalyze an end of strand or “exolytic” cleavage.
Lts are classified according to amino acid motifs and function, into 6 distinct families. Even within a family, there is little sequence homology; however, the proteins in families do appear to share distinct folds (Figure 2). Lts are also divided into membrane (designated M in their nomenclature) and soluble (S) forms. It is hypothesized that these proteins are associated with numerous other cell wall proteins such as PBPs so that even the soluble Lts might be physically associated with the inner membrane of bacteria. Some Lts are also associated with the outer membrane, e.g., RlpA (see below) and likely have distinctive roles [29].
(A) Slt70 of E. coli in complex with Bulgecin A. (B) Lt of Neisseria meningitidis in complex with Bulgecin A. (C) Lt Cj0843 of Campylobacter jejuni in complex with Bulgecin A. (D) Slt inactive mutant E503Q from Pseudomonas aeruginosa in complex with Bulgecin A.
Lts serve many cellular functions including cell wall recycling, cellular division, insertion into cell wall of important structures like secretion systems and flagellar apparati. Lt redundancy is similar to that of the PBPs, and studies looking at gene knockouts of these proteins show that in P. aeruginosa, only loss of the RlpA LT is associated with a change in bacterial morphology [29]. Attempts to prepare multiple Lt knockouts were unsuccessful.
Recently significant research has been conducted on the Lts of P. aeruginosa, including structural and kinetic studies defining structure function relations in these varied proteins (reviewed in [26]). These studies are summarized next.
As previously indicated, P. aeruginosa possesses 11Lts: MltA, MltB/Slt35, MltD, MltF, MltF2, MltG, RlpA, Slt, SltB1 (SltB), SltB2 (SltG), and SltB3 (SltH).
In a tour-de-force of biochemical characterization, including synthesis, purification and characterization of the reaction of soluble forms of all 11 P. aeruginosa Lts with 4 synthetic substrates and P. aeruginosa sacculus to yield 31 distinct peptidoglycan (PG) products, Lee et al. [25] have thoroughly described the structure function relationships for P. aeruginosa Lts. Of interest is that each solubilized Lt enzyme could perform both endolytic and exolytic reactions on the PG substrates.
Using the simplest synthetic substrate, NAG-NAM(pentapeptide)-NAG-NAM(pentapeptide), Lee et al. found that only MltB and the SltB1–3 Lts could recognize this substrate. A second substrate, a NAG-NAM(tetrapeptide)-NAG-anhydroNAM(tetrapeptide), incorporated the anhydroNAM that is likely recognized better by the exolytic Lts. For this substrate, MltA as well as MltB and the SltB1–3 Lts were able to react to convert 100% of the substrate to NAG-anhdroNAMtetrapeptide product. The soluble Lts, SltB1–3 of P. aeruginosa show the greatest activity in assays designed to study soluble proteins, as compared to solubilized membrane Lts [25]. These Lts were able to cleave NAG-NAM(pentapeptide)-NAG-NAM(pentapeptide) with specific activities of 0.4, 0.4 and 0.3 nanomoles of product/min/mg of protein respectively. Slt, the structural homolog of E. coli Slt70, showed no reaction with the synthetic peptidoglycan and slower turnover with the tetrapeptide substrate: 0.1 nmoles/min/mg.
X-ray crystal structures of Slt in its apo form as well as in complex with various synthetic PG substrates and reaction products demonstrated that this Lt has both exolytic and endolytic activity [23]. It is a donut shaped protein like Slt of E. coli. Notably, it is only after the binding of substrates that contain pentapeptide stems that it can exhibit endolytic activity due to a conformational change of the protein on substrate binding. A movie of this rearrangement is available in the supplementary material of reference [23]. Additional studies suggest protein–protein interactions with inner membrane PBPs are also important [26].
SltB1 [22] and SltB3 [24] have also been studied using x-ray crystallography. SLtB1 protein structures suggest that the protein forms a so-called “catenane” homodimeric structure in which the active sites face one another and are thus completely occluded. It is speculated that this soluble dimer may represent a form of activity regulation [22]. SltB3 is an exolytic enzyme with four distinct enzymatic domains within the donut shaped annular protein [24]. SltB3 can recognize PG substrates that are 4–20 sugars in length. These PG chains thread through the annular structure during catalysis.
X-ray crystal structures of a solubilized MltF [21] show that this Lt binds a tetrapeptide stem of the substrate in an allosteric domain. Binding causes a large conformational change that leads to enzyme activation. In the kinetic studies, this solubilized membrane had very low activity with any of the 4 synthetic substrates or the P. aeruginosa sacculus. This raises some questions regarding the actual role of this Lt and whether the conformational changes are relevant when the protein is membrane bound.
Bulgecins were first described by Imato et al. in the 1980s [30, 31]. These natural analogs of GlcNAC-MurNAC are produced by various bacterial species including Burkholderia mesoacidophila and Paraburkholderia acidophila [32, 33], part of the B. cepacia complex. Bulgecins are produced together with sulfazecin, a monobactam antibiotic. Three different bulgecins are produced by these bacteria. Bulgecin A is produced in the highest amount and is the most active inhibitor of Lts (Figure 3, Bulgecin A).
Bulgecin A, the most active of the bulgecins of Paraburkholderia acidophila and Burkholderia mesoacidophila. The pyrrolidine ring (right side of the molecule) and the N-acetylglucosamine potion (GlcNAC) (left side other molecule) are features of Bulgecin A transition state structure.
Early research by Takeda Pharmaceuticals Japan led to the natural product isolation and purification of the bulgecins [30, 31]. It was discovered that when Bulgecin A was paired with a third generation cephalosporin, cefmenoxime, which targets PBP 3 of Enterobacteriaceae, large bulges were formed in the bacterial cell wall leading to osmotic lysis of the bacteria [30, 31]. Subsequently, investigators discovered the soluble Lt of E. coli and solved crystal structures of SltE in complex with Bulgecin A [34]. Through kinetic experiments, it was determined that Bulgecin A was a noncompetitive inhibitor of SltE with an IC50 of 0.5 μM. [35]. While Bulgecin A appeared to be a potent inhibitor of Lts in pathogenic Enterobacteriaceae and led to bacterial killing when paired with β-lactams affecting PBP3 particularly, development of the drug was halted for unknown reasons. Over the next decade, more advanced generation cephalosporins, as well as β-lactam-β-lactamase inhibitor combinations, carbapenems and fluoroquinolones were introduced into the clinic to address the growing problem of Gram negative resistance. Recently a natural product synthesis of the bulgecins was reported for the first time by Tomoshige et al. [36] prompting renewed interest in the use of Bulgecin A as an antimicrobial adjuvant, and possible drug optimization via medicinal chemistry.
Since the original discovery of the bulgecins and Slt in E coli, Lts have been characterized in many additional bacteria including P. aeruginosa, Acinetobacter baumannii, Helicobacter pylori, Neisseria meningitides and Campylobacter jejuni [21, 22, 23, 24, 25, 28, 34, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50]. In general, these organisms have many Lt enzymes with different functions, including endolytic (within strand) and exolytic (end of strand) cleavage of peptidoglycan. Many of these enzymes including those of P. aeruginosa have been expressed for biochemical assays of function, and inhibition by Bulgecin A. Crystal structures of many of the Lts of these organisms have also been obtained, some with substrates or Bulgecin A in the active site (Figure 2).
A recent publication shows that while P. aeruginosa possesses 11 known Lts, three appear to be the main targets of inhibition by Bulgecin A [27]. This work is discussed further below.
Bulgecin A in combination with cefmenoxime and other β-lactams has been studied against Enterobacteriaceae and reported in the original studies by Takeda Pharamceuticals [30, 31]. Later investigators studied Bulgecin A in combination with ampicillin in mouse models of Helicobacter pylori infection and found that the combination was effective in eradicating the organism, and Bulgecin A did not appear to have specific toxicity in mice [51]. These investigators also studied Bulgecin A with Neisseria gonorrhea and N. meningitides strains that were resistant to penicillin and amoxicillin [48]. For strains with higher penicillin MICs not due to the presence of TEM-1 β-lactamase, Bulgecin A at concentrations of 19 mg/L, reduced the MICs from 0.5 to 0.09 mg/L for penicillin G, and 0.75 to 0.4 mg/L for amoxicillin.
Other investigators examined the effect of Bulgecin A as a metallo-β-lactamase inhibitor using L1 MBL of Stenotrophomonas maltophila as a model B1 (di Zn2+) MBL enzyme (Figure 4). Simm et al. determined that the KI for Bulgecin A was 150uM [52]. Later, our group investigated inhibition of VIM-1 using a Bulgecin A preparation from B. mesoacidophila and found that it also acted as an inhibitor of a second B1 MBL enzyme that is commonly found in P. aeruginosa in Europe, Asia and Canada, and rarely in the US [53].
L1 MBL (left) of Stenotrophomonas maltophilia with Bulgecin A; Bulgecin A sulphonates (yellow moieties, right) interacting with the ZnII site and with Asp 14 of the L1 protein.
Our group tested the Bulgecin A extracts from B. mesoacidophila against a variety of carbapenem resistant P. aeruginosa and Acinetobacter baumannii isolates with differing resistance mechanisms [53]. Although these were impure preparations, we found that small amounts were able to inhibit growth of these clinical isolates when combined with typical amounts of carbapenems to which the bacteria were otherwise resistant. The Bulgecin A-meropenem combinations proved effective whether carbapenem resistance was due to the presence of MBLs (VIM-1), hyperproduction of PDC (Amp C enzyme of P. aeruginosa in combination with OMP loss) or efflux. Tomoshige et al. using synthetic Bulgecin A were able to demonstrate bulge formation in P. aeruginosa PA01 as well as lysis in the presence of ceftazidime [36].
Previously it was demonstrated that bulgecin A potentiated the bulge formation and lysis of P. aeruginosa in the presence of ceftazidime and meropenem [36] in a swarm assay [54]. Recently, Dik et al. [27] used individual transposon knockouts of. Lts in a susceptible P. aeruginosa strain, PA01 and further engineered a green fluorescent protein (GFP) gene into the bacteria. The various Lt knockout strains were exposed to ceftazidime, an inhibitor of PBP3 in P. aeruginosa and meropenem, an inhibitor of PBP2,3 and 4 [55] on agar medium containing propidium iodide. Bulge formation and bacterial cell lysis were monitored as a function of time by monitoring green fluorescence from viable cells, and red fluorescence during cell lysis, the red fluorescence arising from bacterial DNA interacting with the propidium iodide in the medium. In the presence of ceftazidime, the Slt and MltD knockouts formed bulges and showed lysis. The Slt knockout demonstrated significant bulge formation within 6 hours of exposure to ceftazidime, and lysis within 9 hours. Some of the other knockouts demonstrated minor bulge formation (MltA, MltG, MltF, SltB1, SltB3) at 9 hours but none showed cell lysis. The effect was even more dramatic in terms of rapidity of bulge formation and cell lysis when meropenem was used. In fact, this semi-qualitative assay that involves spotting the bacteria and β-lactam at a given distance onto agar had to be modified for meropenem, as lysis occurred too quickly compared to conditions for ceftazidime. In the case of meropenem, an inhibitor of PBP2, Slt showed the greatest bulge formation and lysis, followed by MltG.
The soluble forms of five of the Lt enzymes were purified and bulgecin A binding constants measured: Slt Kd = 8.5 ± 1.1 μM; MltD Kd = 1.4 ± 0.3 μM; MltG Kd = 24 ± 5 μM, SltB1 Kd = 160 ± 20 μM; RlpA Kd = 1200 ± 280 μM.
Dik et al. [27] also demonstrated via scanning electron microscopy that cell wall failure within the bulge is responsible for cell lysis, in the presence of β-lactams and Bulgecin A. Withdrawal of the β-lactam antibiotic leads to delayed recovery of cell morphology in the presence of Bulgecin A alone, suggesting further, the cooperative nature of the Lt and PBP functions in cell wall maintenance.
Now that the syntheses of the bulgecins A, B and C have been accomplished and purified Lt enzymes of many bacteria are available with simple commercial high throughput assays such as ENZCHEK lysozyme™ (substrate is a fluorescein labelled sacculus from Micrococcus lutei), it should not be long before potent derivatives of bulgecins are developed through medicinal chemistry approaches. Combinations of enhancers with novel β-lactamase inhibitor/potent anti-pseudomonal β-lactams are possibilities in the future antibiotic arsenal.
Antibiotic resistance in P. aeruginosa is on the rise in both inpatient and outpatient settings. β-lactams remain among the most successful antibiotics due to their potency, efficacy and safety. Traditionally, β-lactamase inhibitors have proved able to extend the life of these valuable antibiotics. However, through a variety of resistance mechanisms, P. aeruginosa has eluded these approaches. Lts are novel cell wall enzymes that work in concert with PBPs to facilitate numerous cellular functions (insertion of secretion systems, cell division, etc.). When both Lts and PBPs are inhibited, bacteria exhibit abnormal bulging of cell wall and osmotic lysis. Bulgecins are naturally occurring compounds that inhibit Lts. Together with β-lactams, Bulgecin A can lead to effective bacterial killing, even when P. aeruginosa are resistant to the partner β-lactam antibiotics. Bulgecins are a novel β-lactam enhancer that may prove beneficial in the treatment of infections with resistant P. aeruginosa.
The author would like to acknowledge her affiliation and employment with the U.S. Department of Veteran Affairs.
The author is an employee of the U.S. Department of Veterans Affairs. The opinions expressed in this review are her own and do not reflect those of her employer.
IntechOpen books are indexed by the following abstracting and indexing services:
",metaTitle:"Indexing and Abstracting",metaDescription:"IntechOpen was built by scientists, for scientists. We understand the community we serve, but to bring an even better service to the table for IntechOpen Authors and Academic Editors, we partnered with the leading companies and associations in the industry and beyond.",metaKeywords:null,canonicalURL:"/page/indexing-and-abstracting",contentRaw:'[{"type":"htmlEditorComponent","content":"Clarivate Web Of Science - Book Citation Index
\\n\\nCroatian Library (digital NSK)
\\n\\nOCLC (Online Computer Library Center) - WorldCat® Digital Collection Gateway
\\n\\n\\n\\n
\\n"}]'},components:[{type:"htmlEditorComponent",content:'
Clarivate Web Of Science - Book Citation Index
\n\nCroatian Library (digital NSK)
\n\nOCLC (Online Computer Library Center) - WorldCat® Digital Collection Gateway
\n\n\n\n
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"105746",title:"Dr.",name:"A.W.M.M.",middleName:null,surname:"Koopman-van Gemert",slug:"a.w.m.m.-koopman-van-gemert",fullName:"A.W.M.M. Koopman-van Gemert",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105746/images/5803_n.jpg",biography:"Dr. Anna Wilhelmina Margaretha Maria Koopman-van Gemert MD, PhD, became anaesthesiologist-intensivist from the Radboud University Nijmegen (the Netherlands) in 1987. She worked for a couple of years also as a blood bank director in Nijmegen and introduced in the Netherlands the Cell Saver and blood transfusion alternatives. She performed research in perioperative autotransfusion and obtained the degree of PhD in 1993 publishing Peri-operative autotransfusion by means of a blood cell separator.\nBlood transfusion had her special interest being the president of the Haemovigilance Chamber TRIP and performing several tasks in local and national blood bank and anticoagulant-blood transfusion guidelines committees. Currently, she is working as an associate professor and up till recently was the dean at the Albert Schweitzer Hospital Dordrecht. She performed (inter)national tasks as vice-president of the Concilium Anaesthesia and related committees. \nShe performed research in several fields, with over 100 publications in (inter)national journals and numerous papers on scientific conferences. \nShe received several awards and is a member of Honour of the Dutch Society of Anaesthesia.",institutionString:null,institution:{name:"Albert Schweitzer Hospital",country:{name:"Gabon"}}},{id:"83089",title:"Prof.",name:"Aaron",middleName:null,surname:"Ojule",slug:"aaron-ojule",fullName:"Aaron Ojule",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Port Harcourt",country:{name:"Nigeria"}}},{id:"295748",title:"Mr.",name:"Abayomi",middleName:null,surname:"Modupe",slug:"abayomi-modupe",fullName:"Abayomi Modupe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"Landmark University",country:{name:"Nigeria"}}},{id:"94191",title:"Prof.",name:"Abbas",middleName:null,surname:"Moustafa",slug:"abbas-moustafa",fullName:"Abbas Moustafa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94191/images/96_n.jpg",biography:"Prof. Moustafa got his doctoral degree in earthquake engineering and structural safety from Indian Institute of Science in 2002. He is currently an associate professor at Department of Civil Engineering, Minia University, Egypt and the chairman of Department of Civil Engineering, High Institute of Engineering and Technology, Giza, Egypt. He is also a consultant engineer and head of structural group at Hamza Associates, Giza, Egypt. Dr. Moustafa was a senior research associate at Vanderbilt University and a JSPS fellow at Kyoto and Nagasaki Universities. He has more than 40 research papers published in international journals and conferences. He acts as an editorial board member and a reviewer for several regional and international journals. His research interest includes earthquake engineering, seismic design, nonlinear dynamics, random vibration, structural reliability, structural health monitoring and uncertainty modeling.",institutionString:null,institution:{name:"Minia University",country:{name:"Egypt"}}},{id:"84562",title:"Dr.",name:"Abbyssinia",middleName:null,surname:"Mushunje",slug:"abbyssinia-mushunje",fullName:"Abbyssinia Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Fort Hare",country:{name:"South Africa"}}},{id:"202206",title:"Associate Prof.",name:"Abd Elmoniem",middleName:"Ahmed",surname:"Elzain",slug:"abd-elmoniem-elzain",fullName:"Abd Elmoniem Elzain",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Kassala University",country:{name:"Sudan"}}},{id:"98127",title:"Dr.",name:"Abdallah",middleName:null,surname:"Handoura",slug:"abdallah-handoura",fullName:"Abdallah Handoura",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Supérieure des Télécommunications",country:{name:"Morocco"}}},{id:"91404",title:"Prof.",name:"Abdecharif",middleName:null,surname:"Boumaza",slug:"abdecharif-boumaza",fullName:"Abdecharif Boumaza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Abbès Laghrour University of Khenchela",country:{name:"Algeria"}}},{id:"105795",title:"Prof.",name:"Abdel Ghani",middleName:null,surname:"Aissaoui",slug:"abdel-ghani-aissaoui",fullName:"Abdel Ghani Aissaoui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105795/images/system/105795.jpeg",biography:"Abdel Ghani AISSAOUI is a Full Professor of electrical engineering at University of Bechar (ALGERIA). He was born in 1969 in Naama, Algeria. He received his BS degree in 1993, the MS degree in 1997, the PhD degree in 2007 from the Electrical Engineering Institute of Djilali Liabes University of Sidi Bel Abbes (ALGERIA). He is an active member of IRECOM (Interaction Réseaux Electriques - COnvertisseurs Machines) Laboratory and IEEE senior member. He is an editor member for many international journals (IJET, RSE, MER, IJECE, etc.), he serves as a reviewer in international journals (IJAC, ECPS, COMPEL, etc.). He serves as member in technical committee (TPC) and reviewer in international conferences (CHUSER 2011, SHUSER 2012, PECON 2012, SAI 2013, SCSE2013, SDM2014, SEB2014, PEMC2014, PEAM2014, SEB (2014, 2015), ICRERA (2015, 2016, 2017, 2018,-2019), etc.). His current research interest includes power electronics, control of electrical machines, artificial intelligence and Renewable energies.",institutionString:"University of Béchar",institution:{name:"University of Béchar",country:{name:"Algeria"}}},{id:"99749",title:"Dr.",name:"Abdel Hafid",middleName:null,surname:"Essadki",slug:"abdel-hafid-essadki",fullName:"Abdel Hafid Essadki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Nationale Supérieure de Technologie",country:{name:"Algeria"}}},{id:"101208",title:"Prof.",name:"Abdel Karim",middleName:"Mohamad",surname:"El Hemaly",slug:"abdel-karim-el-hemaly",fullName:"Abdel Karim El Hemaly",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/101208/images/733_n.jpg",biography:"OBGYN.net Editorial Advisor Urogynecology.\nAbdel Karim M. A. El-Hemaly, MRCOG, FRCS � Egypt.\n \nAbdel Karim M. A. El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n12-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n13-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n14- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis",institutionString:null,institution:{name:"Al Azhar University",country:{name:"Egypt"}}},{id:"113313",title:"Dr.",name:"Abdel-Aal",middleName:null,surname:"Mantawy",slug:"abdel-aal-mantawy",fullName:"Abdel-Aal Mantawy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ain Shams University",country:{name:"Egypt"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:1683},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"8"},books:[{type:"book",id:"10454",title:"Technology in Agriculture",subtitle:null,isOpenForSubmission:!0,hash:"dcfc52d92f694b0848977a3c11c13d00",slug:null,bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",coverURL:"https://cdn.intechopen.com/books/images_new/10454.jpg",editedByType:null,editors:[{id:"338219",title:"Dr.",name:"Fiaz",surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10502",title:"Aflatoxins",subtitle:null,isOpenForSubmission:!0,hash:"34fe61c309f2405130ede7a267cf8bd5",slug:null,bookSignature:"Dr. Lukman Bola Abdulra'uf",coverURL:"https://cdn.intechopen.com/books/images_new/10502.jpg",editedByType:null,editors:[{id:"149347",title:"Dr.",name:"Lukman",surname:"Abdulra'uf",slug:"lukman-abdulra'uf",fullName:"Lukman Abdulra'uf"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10504",title:"Crystallization",subtitle:null,isOpenForSubmission:!0,hash:"3478d05926950f475f4ad2825d340963",slug:null,bookSignature:"Dr. Youssef Ben Smida and Dr. Riadh Marzouki",coverURL:"https://cdn.intechopen.com/books/images_new/10504.jpg",editedByType:null,editors:[{id:"311698",title:"Dr.",name:"Youssef",surname:"Ben Smida",slug:"youssef-ben-smida",fullName:"Youssef Ben Smida"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10552",title:"Montmorillonite",subtitle:null,isOpenForSubmission:!0,hash:"c4a279761f0bb046af95ecd32ab09e51",slug:null,bookSignature:"Prof. Faheem Uddin",coverURL:"https://cdn.intechopen.com/books/images_new/10552.jpg",editedByType:null,editors:[{id:"228107",title:"Prof.",name:"Faheem",surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10572",title:"Advancements in Chromophore and Bio-Chromophore Research",subtitle:null,isOpenForSubmission:!0,hash:"4aca0af0356d8d31fa8621859a68db8f",slug:null,bookSignature:"Dr. Rampal Pandey",coverURL:"https://cdn.intechopen.com/books/images_new/10572.jpg",editedByType:null,editors:[{id:"338234",title:"Dr.",name:"Rampal",surname:"Pandey",slug:"rampal-pandey",fullName:"Rampal Pandey"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10581",title:"Alkaline Chemistry and Applications",subtitle:null,isOpenForSubmission:!0,hash:"4ed90bdab4a7211c13cd432aa079cd20",slug:null,bookSignature:"Dr. Riadh Marzouki",coverURL:"https://cdn.intechopen.com/books/images_new/10581.jpg",editedByType:null,editors:[{id:"300527",title:"Dr.",name:"Riadh",surname:"Marzouki",slug:"riadh-marzouki",fullName:"Riadh Marzouki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10582",title:"Chemical Vapor Deposition",subtitle:null,isOpenForSubmission:!0,hash:"f9177ff0e61198735fb86a81303259d0",slug:null,bookSignature:"Dr. Sadia Ameen, Dr. M. Shaheer Akhtar and Prof. Hyung-Shik Shin",coverURL:"https://cdn.intechopen.com/books/images_new/10582.jpg",editedByType:null,editors:[{id:"52613",title:"Dr.",name:"Sadia",surname:"Ameen",slug:"sadia-ameen",fullName:"Sadia Ameen"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10696",title:"Calorimetry",subtitle:null,isOpenForSubmission:!0,hash:"bb239599406f0b731bbfd62c1c8dbf3f",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10696.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10697",title:"Raman Spectroscopy",subtitle:null,isOpenForSubmission:!0,hash:"ab2446daed0caa4d243805387a2547ee",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10697.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10700",title:"Titanium Dioxide",subtitle:null,isOpenForSubmission:!0,hash:"c935253773c8ed0220e7b8a6fd90c4c6",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10700.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10702",title:"Polyimide",subtitle:null,isOpenForSubmission:!0,hash:"325bb1a83145389746e590eb13131902",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10702.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:17},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:14},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:60},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:11},popularBooks:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"197",title:"Physical Medicine and Rehabilitation",slug:"physical-medicine-and-rehabilitation",parent:{title:"Medicine",slug:"medicine"},numberOfBooks:31,numberOfAuthorsAndEditors:690,numberOfWosCitations:491,numberOfCrossrefCitations:387,numberOfDimensionsCitations:888,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"physical-medicine-and-rehabilitation",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"9153",title:"Sports, Health and Exercise Medicine",subtitle:null,isOpenForSubmission:!1,hash:"366cfd9d5b01961dff4e4172896b1955",slug:"sports-health-and-exercise-medicine",bookSignature:"Samuel Honório, Marco Batista, João Serrano and Maria-Raquel G. Silva",coverURL:"https://cdn.intechopen.com/books/images_new/9153.jpg",editedByType:"Edited by",editors:[{id:"230170",title:"Ph.D.",name:"Samuel",middleName:null,surname:"Honório",slug:"samuel-honorio",fullName:"Samuel Honório"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7375",title:"Medical Robotics",subtitle:"New Achievements",isOpenForSubmission:!1,hash:"f24f06bf5980967a1ea36afe23fc0b02",slug:"medical-robotics-new-achievements",bookSignature:"Serdar Küçük and Abdullah Erdem Canda",coverURL:"https://cdn.intechopen.com/books/images_new/7375.jpg",editedByType:"Edited by",editors:[{id:"5424",title:"Dr.",name:"Serdar",middleName:null,surname:"Küçük",slug:"serdar-kucuk",fullName:"Serdar Küçük"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8335",title:"Effective Prevention and Treatment of Substance Use Disorders for Racial and Ethnic Minorities",subtitle:null,isOpenForSubmission:!1,hash:"ca6c7d5d975b1fa9ce320b1162b0dad6",slug:"effective-prevention-and-treatment-of-substance-use-disorders-for-racial-and-ethnic-minorities",bookSignature:"Erick Guerrero and Tenie Khachikian",coverURL:"https://cdn.intechopen.com/books/images_new/8335.jpg",editedByType:"Edited by",editors:[{id:"294761",title:"Dr.",name:"Erick",middleName:null,surname:"Guerrero",slug:"erick-guerrero",fullName:"Erick Guerrero"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7178",title:"Prosthesis",subtitle:null,isOpenForSubmission:!1,hash:"87ab135eeaa8424520cff806439e32a2",slug:"prosthesis",bookSignature:"Ramana Vinjamuri",coverURL:"https://cdn.intechopen.com/books/images_new/7178.jpg",editedByType:"Edited by",editors:[{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",slug:"ramana-vinjamuri",fullName:"Ramana Vinjamuri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7949",title:"Cardiorespiratory Fitness",subtitle:null,isOpenForSubmission:!1,hash:"fd6d8d7ee62bc8d443de2c5150c00535",slug:"cardiorespiratory-fitness",bookSignature:"Hasan Sözen",coverURL:"https://cdn.intechopen.com/books/images_new/7949.jpg",editedByType:"Edited by",editors:[{id:"161402",title:"Dr.",name:"Hasan",middleName:null,surname:"Sözen",slug:"hasan-sozen",fullName:"Hasan Sözen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7701",title:"Assistive and Rehabilitation Engineering",subtitle:null,isOpenForSubmission:!1,hash:"4191b744b8af3b17d9a80026dcb0617f",slug:"assistive-and-rehabilitation-engineering",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7701.jpg",editedByType:"Edited by",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7879",title:"Spinal Cord Injury Therapy",subtitle:null,isOpenForSubmission:!1,hash:"674d4925395d0e0c564f092bda8c6482",slug:"spinal-cord-injury-therapy",bookSignature:"Antonio Ibarra, Elisa García-Vences and Gabriel Guízar-Sahagún",coverURL:"https://cdn.intechopen.com/books/images_new/7879.jpg",editedByType:"Edited by",editors:[{id:"72488",title:"Dr.",name:"José Juan Antonio",middleName:null,surname:"Ibarra Arias",slug:"jose-juan-antonio-ibarra-arias",fullName:"José Juan Antonio Ibarra Arias"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7897",title:"From Conventional to Innovative Approaches for Pain Treatment",subtitle:null,isOpenForSubmission:!1,hash:"b919454f06566215ea6a94c2d45239cc",slug:"from-conventional-to-innovative-approaches-for-pain-treatment",bookSignature:"Marco Cascella",coverURL:"https://cdn.intechopen.com/books/images_new/7897.jpg",editedByType:"Edited by",editors:[{id:"199335",title:"Dr.",name:"Marco",middleName:null,surname:"Cascella",slug:"marco-cascella",fullName:"Marco Cascella"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7540",title:"Different Areas of Physiotherapy",subtitle:null,isOpenForSubmission:!1,hash:"a73ff9538d7b2ff3aab93e411b669463",slug:"different-areas-of-physiotherapy",bookSignature:"Mintaze Kerem Gunel",coverURL:"https://cdn.intechopen.com/books/images_new/7540.jpg",editedByType:"Edited by",editors:[{id:"98035",title:"Prof.",name:"Mintaze",middleName:null,surname:"Kerem Gunel",slug:"mintaze-kerem-gunel",fullName:"Mintaze Kerem Gunel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6546",title:"Treatment of Brachial Plexus Injuries",subtitle:null,isOpenForSubmission:!1,hash:"24a8e7c7430e86f76fb29df39582855a",slug:"treatment-of-brachial-plexus-injuries",bookSignature:"Vicente Vanaclocha and Nieves Sáiz-Sapena",coverURL:"https://cdn.intechopen.com/books/images_new/6546.jpg",editedByType:"Edited by",editors:[{id:"199099",title:"Ph.D.",name:"Vicente",middleName:null,surname:"Vanaclocha",slug:"vicente-vanaclocha",fullName:"Vicente Vanaclocha"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6843",title:"Biomechanics",subtitle:null,isOpenForSubmission:!1,hash:"85132976010be1d7f3dbd88662b785e5",slug:"biomechanics",bookSignature:"Hadi Mohammadi",coverURL:"https://cdn.intechopen.com/books/images_new/6843.jpg",editedByType:"Edited by",editors:[{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7072",title:"Cerebral Palsy",subtitle:"Clinical and Therapeutic Aspects",isOpenForSubmission:!1,hash:"eebd6581cd862f95edfacb284191e1c5",slug:"cerebral-palsy-clinical-and-therapeutic-aspects",bookSignature:"Isam Jaber Al-Zwaini",coverURL:"https://cdn.intechopen.com/books/images_new/7072.jpg",editedByType:"Edited by",editors:[{id:"30993",title:"Prof.",name:"Isam Jaber",middleName:null,surname:"Al-Zwaini",slug:"isam-jaber-al-zwaini",fullName:"Isam Jaber Al-Zwaini"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:31,mostCitedChapters:[{id:"28453",doi:"10.5772/28383",title:"The Application of Medical Infrared Thermography in Sports Medicine",slug:"the-application-of-medical-infrared-thermography-in-sports-medicine",totalDownloads:10364,totalCrossrefCites:20,totalDimensionsCites:52,book:{slug:"an-international-perspective-on-topics-in-sports-medicine-and-sports-injury",title:"An International Perspective on Topics in Sports Medicine and Sports Injury",fullTitle:"An International Perspective on Topics in Sports Medicine and Sports Injury"},signatures:"Carolin Hildebrandt, Karlheinz Zeilberger, Edward Francis John Ring and Christian Raschner",authors:[{id:"73700",title:"Dr.",name:"Carolin",middleName:null,surname:"Hildebrandt",slug:"carolin-hildebrandt",fullName:"Carolin Hildebrandt"},{id:"119056",title:"Dr.",name:"Christian",middleName:null,surname:"Raschner",slug:"christian-raschner",fullName:"Christian Raschner"},{id:"119058",title:"Dr.",name:"Karlheinz",middleName:null,surname:"Zeilberger",slug:"karlheinz-zeilberger",fullName:"Karlheinz Zeilberger"},{id:"119059",title:"Prof.",name:"Edward Francis John",middleName:null,surname:"Ring",slug:"edward-francis-john-ring",fullName:"Edward Francis John Ring"}]},{id:"19652",doi:"10.5772/20931",title:"Drilling of Bone: Practicality, Limitations and Complications Associated with Surgical Drill-Bits",slug:"drilling-of-bone-practicality-limitations-and-complications-associated-with-surgical-drill-bits",totalDownloads:12564,totalCrossrefCites:22,totalDimensionsCites:45,book:{slug:"biomechanics-in-applications",title:"Biomechanics in Applications",fullTitle:"Biomechanics in Applications"},signatures:"Nicky Bertollo and William Robert Walsh",authors:[{id:"32461",title:"Prof.",name:"William",middleName:null,surname:"Walsh",slug:"william-walsh",fullName:"William Walsh"},{id:"41089",title:"Dr.",name:"Nicky",middleName:null,surname:"Bertollo",slug:"nicky-bertollo",fullName:"Nicky Bertollo"}]},{id:"44692",doi:"10.5772/55461",title:"Iron Supplementation and Physical Performance",slug:"iron-supplementation-and-physical-performance",totalDownloads:2836,totalCrossrefCites:1,totalDimensionsCites:34,book:{slug:"current-issues-in-sports-and-exercise-medicine",title:"Current Issues in Sports and Exercise Medicine",fullTitle:"Current Issues in Sports and Exercise Medicine"},signatures:"Chariklia K. Deli, Ioannis G. Fatouros, Yiannis Koutedakis and\nAthanasios Z. Jamurtas",authors:[{id:"74567",title:"Dr.",name:"Athanasios",middleName:null,surname:"Jamurtas",slug:"athanasios-jamurtas",fullName:"Athanasios Jamurtas"},{id:"136569",title:"Dr.",name:"Ioannis",middleName:null,surname:"Fatouros",slug:"ioannis-fatouros",fullName:"Ioannis Fatouros"},{id:"161217",title:"M.Sc.",name:"Chariklia",middleName:"K",surname:"Deli",slug:"chariklia-deli",fullName:"Chariklia Deli"},{id:"167822",title:"Prof.",name:"Yiannis",middleName:null,surname:"Koutedakis",slug:"yiannis-koutedakis",fullName:"Yiannis Koutedakis"}]}],mostDownloadedChaptersLast30Days:[{id:"66378",title:"Reactive Astrocyte Gliosis: Production of Inhibitory Molecules",slug:"reactive-astrocyte-gliosis-production-of-inhibitory-molecules",totalDownloads:1234,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"spinal-cord-injury-therapy",title:"Spinal Cord Injury Therapy",fullTitle:"Spinal Cord Injury Therapy"},signatures:"Mohammad Taghi Joghataei, Fereshteh Azedi and Soraya Mehrabi",authors:[{id:"283292",title:"Ph.D. Student",name:"Fereshteh",middleName:null,surname:"Azedi",slug:"fereshteh-azedi",fullName:"Fereshteh Azedi"},{id:"283692",title:"Dr.",name:"Mohammad Taghi",middleName:null,surname:"Joghataei",slug:"mohammad-taghi-joghataei",fullName:"Mohammad Taghi Joghataei"},{id:"305689",title:"Dr.",name:"Soraya",middleName:null,surname:"Mehrabi",slug:"soraya-mehrabi",fullName:"Soraya Mehrabi"}]},{id:"53866",title:"Physical Therapy in Patients with Cancer",slug:"physical-therapy-in-patients-with-cancer",totalDownloads:2815,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Shinichiro Morishita and Atsuhiro Tsubaki",authors:[{id:"139514",title:"Ph.D.",name:"Shinichiro",middleName:null,surname:"Morishita",slug:"shinichiro-morishita",fullName:"Shinichiro Morishita"},{id:"202889",title:"Dr.",name:"Atsuhiro",middleName:null,surname:"Tsubaki",slug:"atsuhiro-tsubaki",fullName:"Atsuhiro Tsubaki"}]},{id:"62969",title:"Non-Pharmacological Pain Management",slug:"non-pharmacological-pain-management",totalDownloads:1558,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"pain-management-in-special-circumstances",title:"Pain Management in Special Circumstances",fullTitle:"Pain Management in Special Circumstances"},signatures:"Ahmed El Geziry, Yasser Toble, Fathi Al Kadhi, Muhammad Pervaiz\nand Mohammad Al Nobani",authors:null},{id:"54472",title:"Physiotherapy and Mental Health",slug:"physiotherapy-and-mental-health",totalDownloads:7376,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Michel Probst",authors:[{id:"186905",title:"Prof.",name:"Michel",middleName:null,surname:"Probst",slug:"michel-probst",fullName:"Michel Probst"}]},{id:"63463",title:"Clinical Classification of Cerebral Palsy",slug:"clinical-classification-of-cerebral-palsy",totalDownloads:1544,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"cerebral-palsy-clinical-and-therapeutic-aspects",title:"Cerebral Palsy",fullTitle:"Cerebral Palsy - Clinical and Therapeutic Aspects"},signatures:"Christian Chukwukere Ogoke",authors:[{id:"250398",title:"Dr.",name:"Christian",middleName:"Chukwukere",surname:"Ogoke",slug:"christian-ogoke",fullName:"Christian Ogoke"}]},{id:"47090",title:"Functional Electrical Stimulation in Paraplegia",slug:"functional-electrical-stimulation-in-paraplegia",totalDownloads:3796,totalCrossrefCites:0,totalDimensionsCites:4,book:{slug:"topics-in-paraplegia",title:"Topics in Paraplegia",fullTitle:"Topics in Paraplegia"},signatures:"Aris Papachristos",authors:[{id:"170551",title:"Dr.",name:"Aris",middleName:null,surname:"Papachristos",slug:"aris-papachristos",fullName:"Aris Papachristos"}]},{id:"55065",title:"Exercise Therapy for Physical Therapist",slug:"exercise-therapy-for-physical-therapist",totalDownloads:1541,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"clinical-physical-therapy",title:"Clinical Physical Therapy",fullTitle:"Clinical Physical Therapy"},signatures:"Naruemon Leelayuwat",authors:[{id:"196387",title:"Associate Prof.",name:"Naruemon",middleName:null,surname:"Leelayuwat",slug:"naruemon-leelayuwat",fullName:"Naruemon Leelayuwat"}]},{id:"36705",title:"Stabilization Exercise for the Management of Low Back Pain",slug:"exercise-therapy-for-the-management-of-low-back-pain",totalDownloads:46395,totalCrossrefCites:0,totalDimensionsCites:3,book:{slug:"low-back-pain",title:"Low Back Pain",fullTitle:"Low Back Pain"},signatures:"A. Luque-Suárez, E. Díaz-Mohedo, I. Medina-Porqueres and T. Ponce-García",authors:[{id:"100874",title:"Dr.",name:"Alejandro",middleName:null,surname:"Luque Suarez",slug:"alejandro-luque-suarez",fullName:"Alejandro Luque Suarez"},{id:"158736",title:"Ms.",name:"Esther",middleName:null,surname:"Diaz",slug:"esther-diaz",fullName:"Esther Diaz"},{id:"158737",title:"Prof.",name:"Ivan",middleName:null,surname:"Medina-Porqueres",slug:"ivan-medina-porqueres",fullName:"Ivan Medina-Porqueres"},{id:"158738",title:"Mr.",name:"Tomas",middleName:null,surname:"Ponce",slug:"tomas-ponce",fullName:"Tomas Ponce"}]},{id:"54213",title:"Physical Therapy for Cerebellar Ataxia",slug:"physical-therapy-for-cerebellar-ataxia",totalDownloads:5453,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"neurological-physical-therapy",title:"Neurological Physical Therapy",fullTitle:"Neurological Physical Therapy"},signatures:"Akiyoshi Matsugi",authors:[{id:"196990",title:"Ph.D.",name:"Akiyoshi",middleName:null,surname:"Matsugi",slug:"akiyoshi-matsugi",fullName:"Akiyoshi Matsugi"}]},{id:"67072",title:"Optimization of Maxillofacial Prosthesis",slug:"optimization-of-maxillofacial-prosthesis",totalDownloads:579,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"prosthesis",title:"Prosthesis",fullTitle:"Prosthesis"},signatures:"Faraedon M. Zardawi and Kaida Xiao",authors:[{id:"186097",title:"Dr.",name:"Faraedon",middleName:"M.",surname:"Mostafa",slug:"faraedon-mostafa",fullName:"Faraedon Mostafa"},{id:"275212",title:"Dr.",name:"Kaida",middleName:null,surname:"Xiao",slug:"kaida-xiao",fullName:"Kaida Xiao"}]}],onlineFirstChaptersFilter:{topicSlug:"physical-medicine-and-rehabilitation",limit:3,offset:0},onlineFirstChaptersCollection:[{id:"73331",title:"Physiological Responses to Outdoor Recreation: How it Can Help you Prepare your Outdoor Activity and How to Intervene",slug:"physiological-responses-to-outdoor-recreation-how-it-can-help-you-prepare-your-outdoor-activity-and-",totalDownloads:157,totalDimensionsCites:0,doi:"10.5772/intechopen.93875",book:{title:"Outdoor Recreation - Physiological and Psychological Effects on Health"},signatures:"Andrée-Anne Parent and Tegwen Gadais"},{id:"73005",title:"Outdoor Recreation: Physiological Effects and Prevention of Socially Important Diseases",slug:"outdoor-recreation-physiological-effects-and-prevention-of-socially-important-diseases",totalDownloads:73,totalDimensionsCites:0,doi:"10.5772/intechopen.93331",book:{title:"Outdoor Recreation - Physiological and Psychological Effects on Health"},signatures:"Nikolay Boyadjiev, Katerina Nikolova Georgieva and Penka Angelova Angelova Hristova"},{id:"72729",title:"Introducing Park Facilities and Novelties to Support Individual’s Intention to (Re)Visit",slug:"introducing-park-facilities-and-novelties-to-support-individual-s-intention-to-re-visit",totalDownloads:27,totalDimensionsCites:0,doi:"10.5772/intechopen.93135",book:{title:"Outdoor Recreation - Physiological and Psychological Effects on Health"},signatures:"Marija Opačak"}],onlineFirstChaptersTotal:5},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/254763/gobeng-release-monama",hash:"",query:{},params:{id:"254763",slug:"gobeng-release-monama"},fullPath:"/profiles/254763/gobeng-release-monama",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()