The Pearson coefficient between the experimental and computationally calculated geometric parameters.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"7953",leadTitle:null,fullTitle:"Bioluminescence - Analytical Applications and Basic Biology",title:"Bioluminescence",subtitle:"Analytical Applications and Basic Biology",reviewType:"peer-reviewed",abstract:"This book includes reviews of molecular- and organismal-level studies in bioluminescence in order to elucidate the mechanisms behind this phenomenon. It is intended for molecular biology researchers involved in bioluminescent reactions, molecular engineering of bioluminescent sensor probes, and biomonitoring of environmental toxins.. Field researchers as well as students will also find this volume to be of interest.",isbn:"978-1-78984-785-7",printIsbn:"978-1-78984-784-0",pdfIsbn:"978-1-83962-196-3",doi:"10.5772/intechopen.77783",price:119,priceEur:129,priceUsd:155,slug:"bioluminescence-analytical-applications-and-basic-biology",numberOfPages:124,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"3a8efa00b71abea11bf01973dc589979",bookSignature:"Hirobumi Suzuki",publishedDate:"September 25th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7953.jpg",numberOfDownloads:6730,numberOfWosCitations:7,numberOfCrossrefCitations:10,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:23,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:40,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 15th 2018",dateEndSecondStepPublish:"January 15th 2019",dateEndThirdStepPublish:"March 16th 2019",dateEndFourthStepPublish:"May 21st 2019",dateEndFifthStepPublish:"July 20th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"185746",title:"Dr.",name:"Hirobumi",middleName:null,surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki",profilePictureURL:"https://mts.intechopen.com/storage/users/185746/images/system/185746.png",biography:"Dr. Hirobumi Suzuki received his Ph.D. in 1997 from Tokyo Metropolitan University, Japan, where he studied firefly phylogeny and the evolution of mating systems. He is especially interested in the genetic differentiation pattern and speciation process that correlate to the flashing pattern and mating behavior of some fireflies in Japan. He then worked for Olympus Corporation, a Japanese manufacturer of optics and imaging products, where he was involved in the development of luminescence technology and produced a bioluminescence microscope that is currently being used for gene expression analysis in chronobiology, neurobiology, and developmental biology. Dr. Suzuki currently serves as a visiting researcher at Kogakuin University, Japan, and also a vice president of the Japan Firefly Society.",institutionString:"Kogakuin University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"410",title:"Biotechnology",slug:"biochemistry-genetics-and-molecular-biology-microbiology-biotechnology"}],chapters:[{id:"66251",title:"Biotechnological Advances in Luciferase Enzymes",doi:"10.5772/intechopen.85313",slug:"biotechnological-advances-in-luciferase-enzymes",totalDownloads:1383,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:1,abstract:"This chapter explores the history of the bioengineering advances that have been applied to common luciferase enzymes and the improvements that have been accomplished by this work. The primary focus is placed on firefly luciferase (FLuc), Gaussia luciferase (GLuc), Renilla luciferase (RLuc), Oplophorus luciferase (OLuc; NanoLuc), and bacterial luciferase (Lux). Beginning with the cloning and exogenous expression of each enzyme, their step-wise modifications are presented and the new capabilities endowed by each incremental advancement are highlighted. Using the historical basis of this information, the chapter concludes with a prospective on the overall impact these advances have had on scientific research and provides an outlook on what capabilities future advances could unlock.",signatures:"Andrew Kirkpatrick, Tingting Xu, Steven Ripp, Gary Sayler and Dan Close",downloadPdfUrl:"/chapter/pdf-download/66251",previewPdfUrl:"/chapter/pdf-preview/66251",authors:[{id:"34168",title:"Dr.",name:"Steven",surname:"Ripp",slug:"steven-ripp",fullName:"Steven Ripp"},{id:"89407",title:"Dr.",name:"Tingting",surname:"Xu",slug:"tingting-xu",fullName:"Tingting Xu"},{id:"187444",title:"Dr.",name:"Dan",surname:"Close",slug:"dan-close",fullName:"Dan Close"},{id:"256492",title:"Dr.",name:"Gary",surname:"Sayler",slug:"gary-sayler",fullName:"Gary Sayler"},{id:"256494",title:"Mr.",name:"Andrew",surname:"Kirkpatrick",slug:"andrew-kirkpatrick",fullName:"Andrew Kirkpatrick"}],corrections:null},{id:"66952",title:"Protein-Protein Interaction Assays Using Split-NanoLuc",doi:"10.5772/intechopen.86122",slug:"protein-protein-interaction-assays-using-split-nanoluc",totalDownloads:1637,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Protein-protein interaction assays are fundamental to basic biology, drug discovery, diagnostics, screening, and immunoassays. Protein-fragment complementation (PCA) is one of such useful protein-protein interaction assays. PCA when performed using luciferase is a reversible approach, whereas when performed using green fluorescent protein analogs is an irreversible approach. The NanoLuc technology developed in 2012 utilizes a small and structurally robust luciferase that is capable of producing very bright luminescence. NanoLuc PCA has been used to detect many protein-protein interactions and for screening purposes. Methods developed from NanoLuc PCA include the HiBiT technology and NanoLuc ternary technology. These novel technologies are promising in various fields and further developments are anticipated.",signatures:"Yuki Ohmuro-Matsuyama and Hiroshi Ueda",downloadPdfUrl:"/chapter/pdf-download/66952",previewPdfUrl:"/chapter/pdf-preview/66952",authors:[{id:"234155",title:"Prof.",name:"Hiroshi",surname:"Ueda",slug:"hiroshi-ueda",fullName:"Hiroshi Ueda"},{id:"234158",title:"Dr.",name:"Yuki",surname:"Ohmuro-Matsuyama",slug:"yuki-ohmuro-matsuyama",fullName:"Yuki Ohmuro-Matsuyama"}],corrections:null},{id:"66940",title:"Biosensors Using Free and Immobilized Cells of Luminous Bacteria",doi:"10.5772/intechopen.85624",slug:"biosensors-using-free-and-immobilized-cells-of-luminous-bacteria",totalDownloads:790,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The technologies of receiving free and immobilized photobacteria cells for biomonitoring of toxins are considered. The mechanisms of interaction of toxins with photobacteria are observed. The main attention is paid to the immobilized procedures and structures of carriers. Data on poly(vinyl)alcohol (PVA) cryogel immobilization of different strains of photobacteria are presented. It is established that intensity and stability of light emission of PVA cells is competently controlled by: (1) intensity and persistence of a luminescent cycle using bacterial strain; (2) type of the carrier and the composition of the gel-formation medium; (3) freeze-thawing procedures; and (4) physical and chemical conditions of storage and application. The developed technology of cryogenic gel formation has kept the survival of luminous bacteria in the carrier practically at 100% without the introduction of additional cryoprotecting agents and procedures of a light induction. With storage at −80°C, bioluminescent activity remained without changes about 2 years. Using the immobilized preparations of biosensor, the discrete and continuous analysis of heavy metals, chlorophenols, and pesticides is carried out. The sensitivity of free and immobilized cells to the chosen toxicants is approximately identical. The continuous monitoring of toxicant conditions is optimized.",signatures:"Anvar D. Ismailov, Leyla E. Aleskerova, Kristina A. Alenina and Elena N. Efremenko",downloadPdfUrl:"/chapter/pdf-download/66940",previewPdfUrl:"/chapter/pdf-preview/66940",authors:[{id:"288106",title:"Prof.",name:"Anvar",surname:"Ismailov",slug:"anvar-ismailov",fullName:"Anvar Ismailov"},{id:"288351",title:"Dr.",name:"Aleskerova",surname:"Leyla",slug:"aleskerova-leyla",fullName:"Aleskerova Leyla"},{id:"288352",title:"Ms.",name:"Alenina",surname:"Kristina",slug:"alenina-kristina",fullName:"Alenina Kristina"},{id:"288353",title:"Prof.",name:"Efremenko",surname:"Elena",slug:"efremenko-elena",fullName:"Efremenko Elena"}],corrections:null},{id:"68274",title:"Ecological and Histological Notes on the Luminous Springtail, Lobella sp. (Collembola: Neanuridae), Discovered in Tokyo, Japan",doi:"10.5772/intechopen.88321",slug:"ecological-and-histological-notes-on-the-luminous-springtail-em-lobella-em-sp-collembola-neanuridae-",totalDownloads:934,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Some species of springtail (Collembola) are luminous, but it is not known whether light emitted by springtail is due to self-luminescence, feeding on luminous fungi, or accidental infection by luminous bacteria. To address this question, we characterized the luminescence of a luminous springtail, Lobella sp. (family Neanuridae) discovered in Tokyo, Japan. The emitted light was yellowish-green (540 nm) and was found to originate from tubercles on the thorax (segments II and III) and abdomen (segments I–VI) using a low-light imaging system. The luminescence persisted for several seconds but showed occasional oscillations in a laboratory environment. We also observed fat bodies containing eosin-positive granules under the integument of the tubercles in the tergum by hematoxylin and eosin (HE) staining that were not present in a nonluminous springtail (Vitronura sp.). The fat bodies in Lobella sp. are presumably photocytes analogous to the firefly lantern, and the eosin-positive granules are the likely source of bioluminescence, which implies that springtails are self-luminescent.",signatures:"Tadasu Sano, Yukimasa Kobayashi, Ikuko Sakai, Katsunori Ogoh and Hirobumi Suzuki",downloadPdfUrl:"/chapter/pdf-download/68274",previewPdfUrl:"/chapter/pdf-preview/68274",authors:[{id:"185746",title:"Dr.",name:"Hirobumi",surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki"},{id:"297356",title:"Prof.",name:"Yukimasa",surname:"Kobayashi",slug:"yukimasa-kobayashi",fullName:"Yukimasa Kobayashi"},{id:"297357",title:"Ms.",name:"Ikuko",surname:"Sakai",slug:"ikuko-sakai",fullName:"Ikuko Sakai"},{id:"297358",title:"Dr.",name:"Katsunori",surname:"Ogoh",slug:"katsunori-ogoh",fullName:"Katsunori Ogoh"},{id:"297362",title:"Mr.",name:"Tadasu",surname:"Sano",slug:"tadasu-sano",fullName:"Tadasu Sano"}],corrections:null},{id:"66645",title:"Effect of Camera Illumination on Flashing Behavior of Pteroptyx malaccae (Coleoptera: Lampyridae)",doi:"10.5772/intechopen.85796",slug:"effect-of-camera-illumination-on-flashing-behavior-of-em-pteroptyx-malaccae-em-coleoptera-lampyridae",totalDownloads:931,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Pteroptyx malaccae is a synchronous firefly that is important in firefly tourism in Thailand. Without well-managed tourism, the fireflies have faced to the problems of shooting camera flashes from tourists. Although the effect of artificial light was well understood, which causes negative impact to firefly courtship, there is no obvious information on the effect of the camera illumination. The experiment of testing four types of camera illumination was set up in laboratory using wild populations of P. malaccae. The flash patterns were recorded by videotaping and analyzed by using TiLIA software. The results showed that all kinds of camera illuminations affect flashing behavior of the fireflies. They prolonged flash interval by increasing pulse duration. The flashes from smartphone camera displayed the strongest effect; however, all flash types did not influence on the firefly life span, mating behavior and oviposition behavior of the fireflies.",signatures:"Anchana Thancharoen and Sirima Masoh",downloadPdfUrl:"/chapter/pdf-download/66645",previewPdfUrl:"/chapter/pdf-preview/66645",authors:[{id:"289106",title:"Ph.D.",name:"Anchana",surname:"Thancharoen",slug:"anchana-thancharoen",fullName:"Anchana Thancharoen"},{id:"295154",title:"Ms.",name:"Sirima",surname:"Masoh",slug:"sirima-masoh",fullName:"Sirima Masoh"}],corrections:null},{id:"68446",title:"Biofluorescence in Terrestrial Animals, with Emphasis on Fireflies: A Review and Field Observation",doi:"10.5772/intechopen.86029",slug:"biofluorescence-in-terrestrial-animals-with-emphasis-on-fireflies-a-review-and-field-observation",totalDownloads:1059,totalCrossrefCites:5,totalDimensionsCites:9,hasAltmetrics:1,abstract:"The mysterious world of biofluorescence in terrestrial ecosystems is mesmerizing. Though not as ubiquitous as in the ocean, it is not a rare phenomenon on land. Fluorescence occurs in all major phyla of terrestrial animals (Platyhelminthes, Mollusca, Annelida, Nematoda, Onychophora, Arthropoda, and Chordata) and their subgroups, with diverse fluorophores and performance. In this chapter, we make a general review on the fluorescence in terrestrial animals first, including their systematic distribution, research history, fluorophores, and proposed functions for each group among several other aspects. A systematic observation on the fluorescence of fireflies is reported for the first time. The co-occurrence of biofluorescence and bioluminescence in luminescent land snails, earthworms, potworms, millipedes, and fireflies is a fascinating issue. Though the biochemical mechanism of photogenesis is not fully understood in many terrestrial animals except fireflies, it appears that biofluorescence and bioluminescence do not have clear interaction during the light production process. However, fluorophores and luminophores are usually biochemically related and are different from the photogenic mechanism of jellyfish and several marine creatures whose ultimate light emission is made through energy transfer from bioluminescence to biofluorescence by green fluorescent protein (GFP) or its variants. The role of fluorescence is disputative. In general, nocturnal animals or animals having cryptic living styles, e.g., in earth or under shelters like tree bark or rocks, tend to exhibit UV fluorescence more frequently than animals that are diurnal or inhabit open environments. This pattern is evident in fireflies wherein only nocturnal and luminescent species exhibit noticeable UV fluorescence (likely from luciferin), which is dim or absent in diurnal or crepuscular fireflies. It is unlikely that occasionally induced UV fluorescence in natural environments can play a significant role in intra- or interspecific communication in fireflies or other nocturnal animals.",signatures:"Ming-Luen Jeng",downloadPdfUrl:"/chapter/pdf-download/68446",previewPdfUrl:"/chapter/pdf-preview/68446",authors:[{id:"288568",title:"Ph.D.",name:"Ming-Luen",surname:"Jeng",slug:"ming-luen-jeng",fullName:"Ming-Luen Jeng"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:{id:"15",series:{id:"11",title:"Biochemistry",issn:"2632-0983",editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}}},tags:null},relatedBooks:[{type:"book",id:"9655",title:"Bioluminescence",subtitle:"Technology and Biology",isOpenForSubmission:!1,hash:"26b9e7dade717a5ffdc2dbcfaa1ea43d",slug:"bioluminescence-technology-and-biology",bookSignature:"Hirobumi Suzuki and Katsunori Ogoh",coverURL:"https://cdn.intechopen.com/books/images_new/9655.jpg",editedByType:"Edited by",editors:[{id:"185746",title:"Dr.",name:"Hirobumi",surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1770",title:"Gel Electrophoresis",subtitle:"Principles and Basics",isOpenForSubmission:!1,hash:"279701f6c802cf02deef45103e0611ff",slug:"gel-electrophoresis-principles-and-basics",bookSignature:"Sameh Magdeldin",coverURL:"https://cdn.intechopen.com/books/images_new/1770.jpg",editedByType:"Edited by",editors:[{id:"123648",title:"Dr.",name:"Sameh",surname:"Magdeldin",slug:"sameh-magdeldin",fullName:"Sameh Magdeldin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"584",title:"Advances in Applied Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"fcc9fab84b820983f2a462d5145d2a0e",slug:"advances-in-applied-biotechnology",bookSignature:"Marian Petre",coverURL:"https://cdn.intechopen.com/books/images_new/584.jpg",editedByType:"Edited by",editors:[{id:"74654",title:"Prof.",name:"Marian",surname:"Petre",slug:"marian-petre",fullName:"Marian Petre"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3404",title:"Environmental Biotechnology",subtitle:"New Approaches and Prospective Applications",isOpenForSubmission:!1,hash:"925d14b19ca0f7945996b169d9836f5b",slug:"environmental-biotechnology-new-approaches-and-prospective-applications",bookSignature:"Marian Petre",coverURL:"https://cdn.intechopen.com/books/images_new/3404.jpg",editedByType:"Edited by",editors:[{id:"74654",title:"Prof.",name:"Marian",surname:"Petre",slug:"marian-petre",fullName:"Marian Petre"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2115",title:"Biotechnology",subtitle:"Molecular Studies and Novel Applications for Improved Quality of Human Life",isOpenForSubmission:!1,hash:"07ebd9c0af07dd6b0649bc67ae612b1e",slug:"biotechnology-molecular-studies-and-novel-applications-for-improved-quality-of-human-life",bookSignature:"Reda Helmy Sammour",coverURL:"https://cdn.intechopen.com/books/images_new/2115.jpg",editedByType:"Edited by",editors:[{id:"32232",title:"Dr.",name:"Reda",surname:"Sammour",slug:"reda-sammour",fullName:"Reda Sammour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1910",title:"Oxidative Stress",subtitle:"Molecular Mechanisms and Biological Effects",isOpenForSubmission:!1,hash:"a5fc01580caefb2637f31d59b377032a",slug:"oxidative-stress-molecular-mechanisms-and-biological-effects",bookSignature:"Volodymyr Lushchak and Halyna M. 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Legged locomotion systems are a class of biological robots by supporting on the ground with discrete points, and can traverse nature terrain in large range. This kind of robots is a class of important research objects in robotics community in a long time. In the early time, most of the legged robot systems are static balance locomotion systems, which show a slow moving speed and high requirement in energy dissipation. During the past twenty years, many scholars were interested in dynamic legged robots for improving the performance of the systems.
The one-legged hopping robots are a typical and the simplest systems of the dynamic legged robots, and can be found in many literatures, such as (Raibert,1986; Francois & Samson,1998; Gregorio et al,1997; Ahmadi & Buehler,1997,2006; Ahmadi et al, 2007; Vakasi et al, 1991; Lapshin, 1992; Papadopoulos & Cherouvim, 2004; Hyon & Emura,2002; Zeglin,1999; Guang-Ping H. & Zhi-Yong G, 2008). As it pointed out that in (Papadopoulos & Cherouvim, 2004), most of researches about the one-legged hopping robots were limited to the systems with
For overcoming the limitations of the hopping systems with SLIP model, several scholars studied the hopping systems with non-SLIP model (Zeglin, 1991; Hyon & Mita, 2002; Takahashi et al, 2006; Guang-Ping H. & Zhi-Yong G, 2008, 2009a, 2009b, 2010), such as Uniroo (Zeglin, 1991) and Kenken (Hyon & Mita, 2002). The hopping systems with non-SLIP model generally have more biological characteristics. Thus the mechanism is more complex, and control design for this class system is more intractable since the highly nonlinear and strong coupling in dynamics. For instance, the Uniroo and Kenken are experimental robots, whereas the Uniroo employed the control method for SLIP systems and the best experimental results is 40 times jumps before falling down (Zeglin, 1991), the Kenken was controlled based on accurate simulations of the dynamics, and both of the two robots are actuated by hydraulic systems.
For the sake of reducing the energy dissipation caused by impact, the one-legged hopping systems commonly has small foot such that the robot only contacts with ground on a point. On the assumption that the foot of the robot has no slip, the point contacting with the ground can be regarded as a passive rotational joint. Thus the one-legged hopping robots are generally underactuated mechanical systems. In the field of nonlinear control, the underactuated mechanical systems are a class of interesting nonlinear systems that has been given many attentions in recent years. The benchmark systems of them include the Cart-pole (Graichen, 2007), Acrobot (Lai, 2008), Pendubot (Spong & Block, 1995), Plate-Ball (Oriolo & Vendittelli, 2005), underactuated planar manipulators (Arai et al, 1998), and underactuated surface vessel (Reyhanoglu, 1997) etc. It had been proved that the underactuated mechanical systems are second-order nonholonomic systems in gravitational circumstance if the passive generalized coordinates are not cyclic (Oriolo & Nakamura, 1991), and the nonholonomic systems cannot be stabilized by smooth time-invariant state feedback (Kolmanivsky & McClamroch, 1995). Thus the control methods presented in the literatures introduced non-continuous feedback, time-varying feedback, or the combination of the two classes method, and the control plants are mainly limited to the nonholonomic systems with special differential geometric or differential algebraic properties, such as differentially flat (Nieuwstadt & Murray, 1995; Guang-Ping H. & Zhi-Yong G, 2008, 2009a) or nilpotent (Murray, 1994; Guang-Ping H. & Zhi-Yong G, 2009b) systems. By nonlinear coordinates and inputs (control) changes, the differentially flat nonholonomic systems can be transformed into high order linear systems, the nilpotent systems can be transformed into chained form system under certain conditions (Murray et al, 1993). For the second-order nonholonomic underactuated mechanical systems without these properties, the control problem was not discussed adequately in the nonlinear control field.
The hopping robots with SLIP model are generally second-order nonholonomic underactuated systems because of the small foot, whereas they can be stablized to the periodical hopping orbits by smooth time-invariant state feedback (Raibert,1986; Gregorio et al,1997; Ahmadi & Buehler, 1997, 2006; Ahmadi et al, 2007; Hodgins & Raibert, 1990). The reason is that the special mechanical structure satisfies some conditions: ① the mass as well as the inertia of the leg are far less than them of the total system, swing the leg does not cause large orientation errors of the body; ② the position of the mass center(MC) of the robot is coincident to the hip join, then most of the nonlinear force of the dynamics disappears; ③ the robot has linearly telescopic leg, the telescopic motion of the leg is approximately decoupled from the rotational motion of the systems. These dynamic properties ensure that the SLIP model robot can be stabilized by controlling partial variables without considering the nonholonomic constraints. Nevertheless, a one-legged hopping system with non-SLIP model shows complex nonlinear dynamics, the nonholonomic constraints of the system cannot be ignored. So far there does not have systemic method for designing the control for this class of hopping robots.
Since the obstacle for controlling a general underactuated mechanical system, it is important to investigate the dynamic synthesis problem such that the dynamics of the underactuated systems can be effectively simplified while the underactuated systems holds the controllability, high energy-efficiency, and dexterous mobility. This is helpful for inventing a new underactuated mechanical system with feasible control method, investigating the new applications of underactuated mechanical systems, or simplifying the control problem of the existing underactuated mechanical systems. For instance, Franch investigated the design method of differentially flat planar space robots (Franch et al, 2003), Agrawal & Fattch studied the dynamics synthesis for planar biped robots (Agrawal & Fattch, 2006). In this paper, we propose a novel biological mechanism for the one-legged planar hopping robots on the basis of the dynamics synthesizing. The mechanism is similar to the skeleton of kangaroos, and the dynamics of the mechanism possesses kinetic symmetry with respect to the passive joint variable, then the nonlinear dynamics of the novel mechanism can be transformed into the so-called
In this chapter, section 2 introduces the novel mechanism, and the dynamics of it is presented in section 3. In section 4, the proposition that confirms the nonlinear dynamics can be transformed into the strict feedback normal form is proved. Then a sliding mode backstepping control is introduced in section 5 and the exponential stability is also proved. The motion planning method for the hopping system in stance phase is presented in section 6. The feasibility of the mechanism and the stability of the control are verified by some numerical simulations in section 7.
Fig.1 shows the new mechanism for designing a biological one-legged hopping robot. The robot mechanism has four rigid bodies, of which the shank, thigh, body and tail have length, mass and inertia with respect to their MC are
A novel mechanism for one-legged hopping robot
The characteristics of the hopping robot mechanism can be summarized as follows:
The mechanism is underactuated because of the passive joint
The turning of the keen joint and the tail joint is synchronous, so the actuator of the keen joint can be installed on the tail. This special design can reduce the mass as well as the inertia of the leg. As proved by (Ahmadi & Buehler, 2006), a leg with less mass and inertia is helpful for improving the energy-efficiency of the hopping robot systems.
The MC of the body is coincident with the hip joint, i.e.
The robot mechanism has articulate keen joint, so the leg can provide a larger clearance from the ground than it provided by a linearly telescopic leg in continuous hopping. This is beneficial for leaping over different size obstacles with the same energy cost.
In stance phase, the foot of the robot is contacting with the ground, thus the coordinates
where
The Euler-Lagrange dynamics of the hopping system in stance phase can be written as
For more clearly, the dynamics (11) has form
where
Further more, the dynamics (12) can be written as matrix form
where
where
where
and
where
and
The dynamics (13) can also be partitioned as following form according to the passive and actuated coordinates
where
the dynamics Eq.(27) can be transformed into the
The main property of the underactuated system in (29) is the new control
Olfati-Saber had been studied the normal form of underactuated mechanical systems in his excellent paper (Olfati-Saber, 2002). He presented three classes of cascade nonlinear systems in strict feedback form, feedforward form, and nontriangular quadratic form. As to the robot system considered in this paper, the following proposition ensures that the dynamics (29) can be transformed into the strict feedback normal form.
Proposition 1: (strict feedback form of (29)) The following global change of coordinates:
transforms the dynamics of (29) into a cascade nonlinear system in strict feedback form
where
Proof: Considering the second equation of (30), it follows that
thus
With considering the first equation of (30), then it can be obtained
Once more, by the second equation of (30), we have
since
and
is following, with considering the first equation of (30). The second equation of (31) is proved.
Let
Remark 1: An obstacle of using the Proposition 1 is that the integral
and
then the integral has form
Since
Remark 2: Since
As analyzed in the introduction, there are feasible controls for underactuated mechanical systems to date only concentrated on a few classes of systems with special mathematical property in dynamics, such as the differentially flat or nilpotent. Whereas, there is still no a sufficient and necessary condition that makes certain a nonlinear systems to be differentially flat ( Sira-Ramirez & Agrawal, 2004, Ch.8), and a general nilpotent nonlinear system is also difficult in control, with the major exception of the systems that can be transformed into the
To design a control for strict feedback form system (31), we define
where
To design a control for the affine nonlinear system (9) with strict feedback normal form, the following proposition can be proved.
Proposition 2: (Sliding mode backstepping control)
Consider the system (9), given
where
and
renders the system (9) exponentially stabilize to the origin
Proof: Consider the subsystem
Let
Further consider the subsystem
to be a new candidate Lyapunov function, and let
Let
For the subsystem
Select
then it follows that
For the system (9), let
If we select the control to be
Obviously, it follows that
then if one selects
thus the origin of the affine nonlinear system with drift term is asymptotically stable. If we select
The solution of the differential inequality is given by
Thus the control (10) will render the system (9) exponentially stabilize to the origin
Remark 3: As
Remark 4: Different from the most of control plants of nonholonomic systems in literatures, the affine nonlinear system (9) with drift terms
Motion planning for a hopping robot with non-SLIP model is not intuitional. Fig.2 shows a sketch of motion of the hopping robot in stance phase. In the figure, MC denotes the mass center of the robot,
Denote
The acceleration equation of (11) has form
where
where
Motion sketch of the robot in stance phase
The configuration with balance potential forces is an important point in joint space of the robot in stance phase. This point is both the control target of the robot for static balance and the reference point of planning a feasible trajectory of MC of the robot in every stance phase for continuous hopping. For searching the static balance configuration, one has to employ a numerical method since the complexity of the robot dynamics. For instance, define an optimization measure as follow
where
Many algorithms can be employed to search for the optimal solution. One simple algorithm can be given as
where
Simulation for searching the balance configuration of the robot in stance phase
The static balance configuration of the robot can be calculated to be
The gravitational acceleration is
The stiffness of spring in keen joint is
The phase angle between the tail and thigh is
The mass, length and location of MC, and the inertia of every body are given by
Fig.3 shows the convergent procedure for finding the balance configuration, and
In this section, some numerical simulations are provided for verifying the feasibility of the robot mechanism and the nonlinear controller proposed in the former sections. The physical parameters of the robot mechanism are listed in section 6. Fig.4 shows the simulation results for stance balance control. In this simulation, the initial configuration errors of the robot is given by
The general stance phase motion for the hopping robot is commonly a continuous trajectory that nears to the stance balance configuration. Given the desired motion of MC of the robot is
where
Fig.7 shows another simulation result for trajectory control of MC moving along the direction
In Fig.7 (a)-(c), the curve in dashed also indicates the desired motion, and the solid curve indicates the controlled motion of the corresponding variable. There is no capsizal torque
Simulation for the stance balance control
Some configuration snapshots of the hopping robot during stance balance control shown by
Simulation for a periodical motion of MC along direction
Simulation for a periodical motion of MC along direction
need to be balanced since that the desired motion follows the vertical direction through the supporting point, one can find that the motion is realized with less error than it in Fig.6. Both Fig.6 (d) and Fig. 7(d) illustrate the torque of actuators during the corresponding controlled motion in two different directions of MC.
It is well known that the angular momentum of a hopping robot system in flight phase is conserved, and the angular momentum is generally unintegrable, thus the hopping robot systems in flight phase are first order nonholonomic system. For the first order nonholonomic systems with two inputs, there is a theorem that confirms the system can be transformed into the so-called chained form (Murray & Sastry, 1993; Murray, 1994). As to the chained from systems, there are many feasible control method in literatures. Therefore, one can expect that the novel hopping system presented in this paper will stable hopping under appropriate motion planning. The optimal motion plan and control problems for the novel hopping system with considering the energy-efficiency, and comparing the presented mechanism with the SLIP model system from the point of view of energy-efficiency and mobility, are interesting works in the future.
On the basis of dynamic synthesis, a novel mechanism for one-legged hopping robot is proposed. Different from the most of relative researches in literature, the proposed hopping robot mechanism is a non-SLIP model system, which generally shows more biological characteristics while the control problem of it is intractable, due to the complex nonlinear dynamics and the second-order nonholonomic constraints. Thanks to the special design, it is proved that the dynamics of the presented hopping robot mechanism can be transformed into the non-affine strict feedback normal form. Further more, it is shown that the normal form can also be rewritten as affine system with slightly approximation. Then a sliding model backstepping control is proposed for stabilizing the nonlinear dynamic system to its origin as well as a given trajectory around the balance configuration of the robot in stance phase. The stability of the presented control is proved, and verified by some numerical simulations.
This work is supported by Nature Science Foundation of China (No.50975004) and PHR(IHLB)( No. PHR200906107).
Nonsteroidal anti-inflammatory drugs (NSAID) are a class of drugs that reduce pain, decrease fever, prevent blood clots and, in higher doses decrease inflammations too. NSAIDs have been widely used to treat a number of diseases such as heart disease, various cancers, and Alzheimer’s, pathogenic conditions. The term non-steroidal distinguishes these drugs from steroids, which having a similar eicosanoid-depressing, anti-inflammatory action and have a broad range of other effects [1]. NSAIDs obstruct the generation of prostaglandins (chemical messengers that regulate inflammation, fever, and the sensation of pain) by restraining the activity of a compound, cyclooxygenase (COX); COX-1 and COX-2. Both the COX-1 and COX-2 enzymes serve important homeostatic roles in the human body. Depending on their chemical structures, NSAIDs are broadly divided into two major classes like non-selective COX inhibitors and selective COX-2 inhibitors. The classification based on the chemical structure is non-selective COX inhibitors and selective COX-2 inhibitors [2, 3, 4, 5]. The non-selective COX inhibitors are salicylates, propionic acid derivatives, enolic acid (oxicam) derivatives, anthranilic acid derivatives, selective COX-2 inhibitors, sulfonanilide, and others. In which, COX-1 is considered as important for the production of prostaglandins of homeostatic maintenance, such as platelet aggregation, the regulation of blood flow in the kidney and stomach, and the regulation of gastric acid secretion. While COX-2 is considered as an inducible isoenzyme, although there is some constitutive expression in the kidney, brain, bone, female reproductive system, and gastrointestinal (GI) tract. Thus, the COX-2 is an enzyme plays an important role in pain and inflammatory processes [1, 2, 3, 6].
The profen drugs are a category of nonselective, non-steroidal anti-inflammatory drugs (NSAIDs), which reduce pain (analgesia), body temperature during fever (antipyretic), signs of inflammation (anti-inflammatory activity), and in mice, slow the development of cancers. They are one of the most commonly prescribed pain medications. The profen drugs are derivatives of 2-phenylpropanoic acid. In this work, we have preferred such propionic acid derivatives. 2-phenylpropanoic acid- profen drugs and their general chemical structure are depicted in Figure 1. Few drugs under this category are; ibuprofen, ketoprofen, naproxen, fenoprofen, flurbiprofen, and oxaprozin. In an effort to elucidate a more deeper insight on the physicochemical properties of 2-phenylpropanoic acid- profen drugs we present a detailed discussion on quantum computational calculations and predictions based on their structural geometry, frontier molecular orbitals non-linear optical properties (NLO), of all selected compounds, were done using B3LYP/6311G++(d,p) level of theory. In addition, the computationally calculated electronic properties such as Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), Bond Dissociation Enthalpy (BDE), ionization potential (IP), electron affinity (EA), hardness (η), softness (S), electronegativity (χ) and electrophilic index (ω) were also calculated to get an insight into its property by means of its anti-inflammatory activities. This study will offer knowledge of their action and also help us to design new drugs with therapeutic effects, experimental and thus computational studies are of interest for the rationale of the action mechanism of bioactive compounds. Further, in order to have a better understanding about the interaction with target proteins, molecular docking was also conducted by determining the probable binding modes of it by inserting all selected ligands into the active sites of the COX enzymes.
Chemical structure of propionic acid derivatives.
The input structures the drugs; ketoprofen (PubChem: 3825), ibuprofen (PubChem: 3672), fenoprofen (PubChem: 3342) and flurbiprofen (PubChem: 3394) were taken from the PubChem database [7] which are in SDF (Standard Data File) format and were converted to GJF (Gaussian Job File) input files using the application Open Babel [8].
All the quantum calculations have been performed by density functional theory using a Gaussian 09 software package [9]. The initial geometries chosen for calculation was taken from the PubChem database and optimized with B3LYP/6311G++(d,p) level of the theory [7]. The B3LYP is Becke’s three-parameter practical hybrid methods that add the exchange and electronic correlation terms in DFT, including the Lee, Yang Parr (LYP) functional. The optimized geometry was compared to crystallographic data in the Cambridge Crystallographic Data Center, such a comparison between the experimental and theoretical values helps to reduce the error in the optimized geometry. The optimized geometry was used for the calculations of harmonic vibrational frequencies at the B3LYP/6311G++(d,p) method, it also helps to ensure the systems to be local minimum number imaginary vibration frequencies. The thermochemical properties [10, 11, 12] like, hardness (η), softness (S), chemical potential (μ), electronegativity (χ) and electrophilicity index (ω), were calculated using Koopmans’ theorem for closed-shell compounds. Electrostatic potential analysis has also been made to identify the mapping surface of drugs. Dipole moments, linear and non-linear optical (NLO) properties of AMB were also calculated at the same level of theory.
Further, molecular docking was also conducted to predict binding poses, bio affinity and virtual screening of the selected drugs into the 3D crystal structure of cyclooxygenase-2 (PDB ID: 1CX2) and cyclooxygenase-1 (PDB ID: 1EQG) using GLIDE Dock Program in Schrödinger Maestro software. The protein structure was refined using the protein preparation wizard, which employs under restrained minimization and heavy atoms were restrained by using OPLS 2003 force field. The ligands were subjected to ligand preparation using the ligand preparation wizard (Lig prep) of Schrödinger software in the Maestro interface (11.5). Grid center is defined for the active site and box sizes are set to 20 Å [2, 13, 14].
The optimized structures of (a) fenoprofen, (b) ketoprofen, (c) flurbiprofen and (d) ibuprofen were calculated using B3LYP/6311G++(d,p) level of the theory and shown in Figure 2. The optimized geometries were compared to crystallographic data in the Cambridge Crystallographic Data Center to correlation coefficient factor. The calculated Pearson correlation coefficient for ketoprofen, fenoprofen and Ibuprofen has given in Table 1; the crystallographic data for flurbiprofen is not available yet. The Pearson correlation coefficient (PCC), or Pearson’s r, the Pearson product-moment correlation coefficient (PPMCC), or the bivariate correlation is a statistic that measures linear correlation between two variables X and Y. Here, this method is used to find out the linear regression between the experimental and computationally calculated geometric parameters. Normally, it has a value between +1 and −1, where +1 indicates total positive linear correlation, 0 is no linear correlation, and −1 is total negative linear correlation [15].
The optimized molecular structures of the selected drugs, calculated at DFT/B3LYP/6311G++(d,p). (a) Ketoprofen. (b) Fenoprofen. (c) Flurbiprofen. (d) Ibuprofen.
Sample | Pearson correlation coefficient |
---|---|
Ketoprofen | 0.951 |
Fenoprofen | 0.976 |
Ibuprofen | 0.899 |
The Pearson coefficient between the experimental and computationally calculated geometric parameters.
The thermo-chemical parameters, such as enthalpy (H), entropy (S), Gibb’s free energy (G) were calculated to find which drug is more stable by comparing G and S values and the obtained values are given in Table 2. In general, more negative the value of G the drug is more stable and more active if the value of S is more positive. From the analysis, it is found that ketoprofen has more negative value for G (−5.29 × 105 kcal/mol) and flurbiprofen has more or less same G value (−5.21 × 105 kcal/mol). Hence, ketoprofen is a more stable and active drug compared to other selected drugs with enhanced entropy value of 136.08 cal/mol.
Sample | Energy ×105 (kcal/mol) | Enthalpy ×105 (kcal/mol) | Gibbs free energy ×105 (kcal/mol) | Entropy (cal/mol) | Molecular mass (amu) |
---|---|---|---|---|---|
ketoprofen | −5.29 | −5.29 | −5.29 | 136.08 | 254.09 |
fenoprofen | −5.06 | −5.06 | −5.06 | 133.11 | 242.09 |
flurbiprofen | −5.21 | −5.21 | −5.21 | 129.43 | 244.08 |
ibuprofen | −4.12 | −4.12 | −4.12 | 128.56 | 206.13 |
Thermo-chemical properties of the selected drugs were calculated using the DFT/B3LYP/6311G++(d,p) level of theory.
In computational chemistry, the frontier molecular orbitals play an important role in demonstrating active sites, kinetic stability and chemical reactivity of the molecule (Table 3). In the present work, frontier molecular orbital energies (EHOMO and ELUMO) of all selected drugs were calculated using DFT/B3LYP/6311G++(d,p) level of theory. The LUMO indicates the most likely site which would undergo a nucleophilic attack while the HOMO describes the most likely site for an electrophilic attack. The energy corresponding to HOMO represents the ionization potential of the molecule, while that of the LUMO represents the corresponding electron affinity. A high HOMO–LUMO energy gap indicates greater stability and low reactivity of the chemical system. On the basis of frontier molecular orbital analysis, ketoprofen is found to be more reactive with lower stability compared to other drug molecules in the family.
SAMPLE | HOMO (eV) | LUMO (eV) | HOMO-1 (eV) | LUMO+1 (eV) | HOMO-2 (eV) | LUMO+2 (eV) | BAND GAP (eV) |
---|---|---|---|---|---|---|---|
Ketoprofen | −6.96 | −2.10 | −7.25 | −1.02 | −7.29 | −0.88 | 4.86 |
Fenoprofen | −6.26 | −0.91 | −7.01 | −0.65 | −7.10 | −0.48 | 5.36 |
Flurbiprofen | −6.54 | −1.35 | −7.15 | −0.71 | −7.21 | −0.53 | 5.19 |
Ibuprofen | −6.68 | −0.77 | −7.05 | −0.50 | −7.92 | −0.34 | 5.90 |
Frontier molecular orbital of the selected NSAIDs was calculated using the DFT/B3LYP/6311G++(d,p) level of theory.
To understand the three-dimensional charge distributions over the drug molecules, to locate the most electronegative and electropositive site on their skeleton and to predict reactive sites for electrophilic and nucleophilic attack for the NSAIDs molecular electrostatic potential (MESP) mapping can sightsee.
The MESP map of ketoprofen shows that the negative potential sites are on electronegative atoms like oxygen atoms as well as the positive potential sites are around the hydrogen atoms. These sites give information about the region from where the compound can have noncovalent interactions (Figure 3).
The MESP structures of (a) ketoprofen, (b) fenoprofen, (c) flurbiprofen and (d) ibuprofen. The negative (red) regions of MESP were related to electrophilic reactivity and the positive (blue) regions to nucleophilic reactivity.
In order to have a deep insight about the reactive nature of selected NSAIDs, the global descriptive parameters like hardness, softness, chemical potential, electronegativity, and electrophilicity index were calculated using Koopmans’ theorem for closed-shell compounds, as follows [11, 16]:
where EHOMO is the energy of HOMO and ELUMO is the energy of LUMO.
The calculated global descriptors of AMB are given in Table 4.
Sample | Ionization potential (Ip) | Electron affinity (Ea) | Hardness ( | Electronegativity ( | Softness (S) | Chemical potential ( | Electrophilicity index ( |
---|---|---|---|---|---|---|---|
Ketoprofen | 6.96 | 2.100 | 2.43 | 4.53 | 4.86 | −4.53 | 4.86 |
Fenoprofen | 6.26 | 0.90 | 2.68 | 3.58 | 5.36 | −3.58 | 5.36 |
Flurbiprofen | 6.54 | 1.35 | 2.60 | 3.95 | 5.19 | −3.95 | 5.19 |
Ibuprofen | 6.68 | 0.77 | 2.96 | 3.73 | 5.91 | −3.73 | 5.91 |
Calculated global descriptors of the selected NSAIDs were calculated using the DFT/B3LYP/6311G++(d,p) level of theory.
According to the maximum hardness principle (MHP), at constant external potential, the stability of a molecule increases with hardness, and with the increase in stability, the reactivity decreases. Softness is just the reciprocal of hardness, so higher the softness, lower is the stability,
Ionization energy is a fundamental descriptor of the chemical reactivity of atoms and molecules. High ionization energy indicates high stability and chemical inertness, and small ionization energy indicates high reactivity of the atoms and molecules. If the electronic chemical potential is greater, then the compound is less stable or more reactive. Electron affinity refers to the capability of a ligand to accept precisely one electron from a donor. The electrophilicity index is described as a structural depictor for the analysis of the chemical reactivity of molecules. It measures the tendency of the species to accept electrons. A good, more reactive, nucleophile has a lower value of
The computational approach can also be used to study the interaction of electromagnetic fields in various media to produce new fields that are altered in frequency, phase and amplitude or other propagation characteristics from the incident fields. The polarization P, induced in a medium by an external electric field F is given by
where χ(n) is the nth order susceptibility tensor of the bulk medium.
The dipole moment of a molecule interacting with an electric field can be written
where μi0 is the permanent dipole moment and αij, βijk, ϒijkl is tensor elements of the linear polarizability and first and second hyperpolarizabilities respectively. This interaction may even lead to nonlinear optical effects (NLO). In this direction in order to study the NLO properties, the dipole moment, first static hyperpolarizability (βtot) and its related properties including α, β and ∆α of all selected NSAIDs were calculated using DFT/B3LYP/6311G++(d,p) method based on the finite-field approach and are given in Table 4. The second-order term of the hyperpolarizability gives rise to sum and difference frequency mixing (including second harmonic generation) and optical rectification. The third-order term is responsible for the third-harmonic generation and two-photon resonances. The polarizability and hyperpolarizability of NLO can be written as tensors. While the linear polarizability tensor α as shown below which is a 3*3 matrix having nine components as shown below.
For the first hyperpolarizability, the quantity of interest β is a 3*3*3 matrix has
The highest value of dipole moment is observed for ketoprofen, which is equal to 3.2078 Debye. The calculated average polarizability and first-order hyperpolarizability of the drug molecules are given in Table 5. All the samples exhibit better values compared to one of the prototypical molecules, Urea (μ and β of urea is 4.56 D and 4.8 × 10−36 esu respectively) [25]. Though all the molecules are NLO active molecule, ketoprofen has the highest among others with hyperpolarizability value of
Samples | Dipole moment (μ) Debye | Polarizability (esu) | Hyperpolarizability (esu) |
---|---|---|---|
Ketoprofen | 3.20 | ||
Ibuprofen | 1.70 | ||
Fenoprofen | 1.16 | ||
Flurbiprofen | 2.68 |
The calculated dipole moment μ (Debye), the polarizability β tot and first hyperpolarizability β tot of all selected NSAIDs.
Molecular docking is one of the most frequently used methods in structure-based drug design due to its ability to predict the binding conformation of small molecules to the appropriate target binding site.
1CX2 is an enzyme involved in arachidonic acid metabolism, where arachidonic acid is the precursor that is metabolized by various enzymes, especially cyclooxygenase-1 and -2 to a wide range of biologically and clinically important eicosanoids and metabolites of these eicosanoids. Two important pathways for arachidonic acid metabolism are the cyclooxygenase (COX) and 5-lipoxygenase (5-LO) pathways. The COX pathway forms intermediate compounds called cyclo-endoperoxides (PGG2 and PGH2). Enzymes, many of which are tissue specific, then convert the cyclo-endoperoxides into the final biologically active prostanoid. 1CX2 is a tetramer having four identical subunits and its chains C and D contain the inbuilt ligand SC-558 and the structure of the COX-2 enzyme is depicted in Figure 4. The amino acid residues in the active site of 1CX2 are TYR355, GLY354, SER353, LEU352, VAL349, TYR348, MET522, VAL523, GLY526, ALA527, SER530, LEU531, LEU359, ARG120, VAL116, HIS90, ARG513, ALA516, ILE517, PHE518, TRP387, TYR385, LEU384 and PHE381.
(a) Structure of the COX-2 enzyme having inbuilt ligand SC-558. (b) Protein-ligand interaction of SC-558 with 1CX2. (c) 2-D protein-ligand interaction of SC-558 with 1CX2.
Figure 5(b) demonstrates the 3-dimensional protein-ligand interaction SC-558 into the active site of 1CX2. The co-crystallized ligand SC-558 is found to be buried deep into the binding pocket of 1CX2. SC-558 interacts with the active site’s amino acids of the protein by H-bonding with active site amino acids ARG513, SER353 and LEU352, which is well evidently observed from 2-D interaction picture as shown in Figure 5(c). SC-558 interacts with COX-2 with a binding energy of −11.987 kcal/mol.
3-D protein-ligand interactions of the ligands (a) ketoprofen, (b) fenoprofen, (c) flurbiprofen and (d) ibuprofen into the active site of COX-2.
After analyzing the protein-ligand interaction of 1CX2 with its co-crystallized ligand SC558, all the selected ligands ketoprofen, fenoprofen, flurbiprofen and ibuprofen were docked to the active site of 1CX2 and it is found that all the selected NSAIDs docked well deep into the binding pocket of 1CX2 with good gliding score, given in Table 5. Figure 5 shows the 3-D protein-ligand interaction of all selected NSAIDs into the active site of COX-2.
Ketoprofen and fenoprofen were docked deeply into the active site region making interactions with the residues ARG120, TYR355, TYR385 and TRP387 while, flurbiprofen docked deeply into the active site region making interactions with the residues ARG120 and TYR355 and ibuprofen with residue TYR355 only (Figure 6).
2-D protein-ligand interactions of the ligands: (a) ketoprofen, (b) fenoprofen, (c) flurbiprofen and (d) ibuprofen into the active site of COX-2.
COX-1 is an enzyme that acts on arachidonic acid and produces housekeeping prostaglandins. It is a dimer having two identical structural units in which Chain B and some nonstandard residues were deleted after the preprocessing and the structure of the protein are shown in Figure 7. The amino acid residues in the active site of 1EQG are TYR355, SER353, LEU352, VAL349, MET522, ILE523, ALA527, SER530, LEU531, LEU359, ARG120, VAL116, PHE518, GLY526, MET522, PHE518, TRP387, TYR385, LEU384 and PHE381.
Structure of COX-1.
All the selected ligands ketoprofen, fenoprofen, flurbiprofen, and ibuprofen were docked to the active site of COX-1 and it is found that all the selected NSAIDs docked well deep into the binding pocket of COX-1 with good gliding score, given in Table 6 and binding energy were tabulated in Table 7. Figure 8 shows the 3-D protein-ligand interaction of all selected NSAIDs into the active site of COX-1.
Sample | Gliding score with COX-2 | Gliding score with COX-1 |
---|---|---|
Ketoprofen | −9.279 | −11.242 |
Fenoprofen | −11.37 | −10.862 |
Flurbiprofen | −9.377 | −11.602 |
Ibuprofen | −7.468 | −10.075 |
The gliding score of all samples with COX-1 and COX-2 enzymes.
Sample | Binding energy with COX-2 kcal/mol | Binding energy with COX-1 kcal/mol |
---|---|---|
Ketoprofen | −9.280 | −11.242 |
Fenoprofen | −8.694 | −10.863 |
Flurbiprofen | −9.377 | −11.603 |
Ibuprofen | −10.133 | −10.075 |
The binding energy of all samples with COX-1 and COX-2 enzymes.
3-D protein-ligand interactions of the ligands (a) ketoprofen, (b) fenoprofen, (c) flurbiprofen, (d) ibuprofen into the active site of COX-1.
Ketoprofen and fenoprofen were docked deeply into the active site region making interactions with the residues TYR385, TRP387, ARG120 and TYR355 by forming two hydrogen bonds with ARG120 and TYR355, two pi-pi stacking interaction between phenyl ring of the ligand with amino acids TYR385 and TRP387 and one salt bridge with active site amino acids. Though the interactions are the same for ketoprofen and fenoprofen the binding energy is different, ketoprofen has a binding energy of −11.242 kcal/mol while that of fenoprofen is −10.863 kcal/mol. At the same time, flurbiprofen and ibuprofen docked deeply into the active site region making interactions with the residues ARG120 and TYR355 and ibuprofen with residue TYR355 only (Figure 9).
2-D protein-ligand interactions of the ligands (a) ketoprofen, (b) fenoprofen, (c) flurbiprofen and (d) ibuprofen into the active site of COX-1.
The complete Quantum computational investigations were done using DFT theoretical calculation at the DFT/B3LYP/6311G++(d,p) method that has been performed for all selected propionic acid derivatives, NSAIDs. Almost all bond lengths and angles all the profen drugs agree very well with the X-ray crystal structures in Cambridge Crystallographic Data Center suggesting that all the molecules are well described with DFT/B3LYP/6311G++(d,p) level of theory. The electrophilic and nucleophilic sites were traced out from the isosurfaces of molecular electrostatic potential. The detailed confab on the calculated global descriptors revealed that ketoprofen is more reactive than other propionic derivatives and has the ability to donate electrons easily. Though the hyperpolarizability values reveal that the all selected organic molecule has better NLO activity compared to urea, ketoprofen shows better activity than others. Further, the molecular docking studies of these compounds demonstrates a good selectivity profile with both COX enzymes with good gliding scores and confirmed ketoprofen is a strong anti-inflammatory agent compared to others.
Authors thankfully acknowledge the Central Sophisticated Instrument Facility (CSIF) of University of Calicut for providing Schrodinger Maestro software and hardware support. KPSH further acknowledges UGC-MANF for fellowship with sanction number MANF2017-18-KER-78598.
The authors declare no conflict of interest.
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They are considered as the biotechnologically valuable bacteria that are exploited for its secondary metabolite production. Approximately, 10,000 bioactive metabolites are produced by Actinobacteria, which is 45% of all bioactive microbial metabolites discovered. Especially Streptomyces species produce industrially important microorganisms as they are a rich source of several useful bioactive natural products with potential applications. Though it has various applications, some Actinobacteria have its own negative effect against plants, animals, and humans. On this context, this chapter summarizes the general characteristics of Actinobacteria, its habitat, systematic classification, various biotechnological applications, and negative impact on plants and animals.",book:{id:"5056",slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Ranjani Anandan, Dhanasekaran Dharumadurai and Gopinath\nPonnusamy Manogaran",authors:[{id:"48914",title:"Dr.",name:"Dharumadurai",middleName:null,surname:"Dhanasekaran",slug:"dharumadurai-dhanasekaran",fullName:"Dharumadurai Dhanasekaran"}]},{id:"72074",title:"The Chemistry Behind Plant DNA Isolation Protocols",slug:"the-chemistry-behind-plant-dna-isolation-protocols",totalDownloads:3546,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Various plant species are biochemically heterogeneous in nature, a single deoxyribose nucleic acid (DNA) isolation protocol may not be suitable. There have been continuous modification and standardization in DNA isolation protocols. Most of the plant DNA isolation protocols used today are modified versions of hexadecyltrimethyl-ammonium bromide (CTAB) extraction procedure. Modification is usually performed in the concentration of chemicals used during the extraction procedure according to the plant species and plant part used. Thus, understanding the role of each chemical (viz. CTAB, NaCl, PVP, ethanol, and isopropanol) used during the DNA extraction procedure will benefit to set or modify protocols for more precisions. A review of the chemicals used in the CTAB method of DNA extraction and their probable functions on the highly evolved yet complex to students and researchers has been summarized.",book:{id:"8912",slug:"biochemical-analysis-tools-methods-for-bio-molecules-studies",title:"Biochemical Analysis Tools",fullTitle:"Biochemical Analysis Tools - Methods for Bio-Molecules Studies"},signatures:"Jina Heikrujam, Rajkumar Kishor and Pranab Behari Mazumder",authors:[{id:"74521",title:"Dr.",name:"Rajkumar",middleName:null,surname:"Kishor",slug:"rajkumar-kishor",fullName:"Rajkumar Kishor"},{id:"309357",title:"Prof.",name:"Pranab Behari",middleName:null,surname:"Mazumder",slug:"pranab-behari-mazumder",fullName:"Pranab Behari Mazumder"},{id:"318351",title:"Ph.D. Student",name:"Jina",middleName:null,surname:"Heikrujam",slug:"jina-heikrujam",fullName:"Jina Heikrujam"}]}],onlineFirstChaptersFilter:{topicId:"6",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"80495",title:"Iron in Cell Metabolism and Disease",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:1,totalDimensionsCites:null,doi:"10.5772/intechopen.101908",abstract:"Iron is the trace element. We get the iron from the dietary sources. The enterocytes lining the upper duodenal of the intestine absorb the dietary iron through a divalent metal transporter (DMT1). The absorbed ferrous iron is oxidized to ferric iron in the body. This ferric iron from the blood is carried to different tissues by an iron transporting protein, transferrin. The cells in the tissues take up this ferric form of iron by internalizing the apo transferrin with its receptors on them. The apo transferrin complex in the cells get dissociated resulting in the free iron in cell which is utilized for cellular purposes or stored in the bound form to an iron storage protein, ferritin. The physiological levels of iron are critical for the normal physiology and pathological outcomes, hence the iron I rightly called as double-edged sword. This chapter on iron introduces the readers basic information of iron, cellular uptake, metabolism, and its role cellular physiology and provides the readers with the scope and importance of research on iron that hold the great benefit for health care and personalized medicine or diseases specific treatment strategies, blood transfusions and considerations.",book:{id:"10842",title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg"},signatures:"Eeka Prabhakar"},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.104978",abstract:"Purine derivatives like adenosine 5′-triphosphate (ATP) is the powerhouse of the cell and is essential to maintain the cellular homeostasis and activity. Besides this they also act as a chemical messenger when released into the extracellular milieu because of stress and cellular insult. The extracellular ATP (eATP) as well as its metabolite adenosine triggers purinergic signaling affecting various cellular processes such as cytokine and chemokine production, immune cell function, differentiation, and maturation, and mediates inflammatory activity. Aberrant purinergic signaling had been implicated in several diseased conditions. This chapter will focus on the dynamics of purinergic signaling and immune signaling in driving under various diseased conditions like autoimmunity and infectious disease.",book:{id:"10801",title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg"},signatures:"Richa Rai"},{id:"81800",title:"Long Non-Coding RNAs: Biogenesis, Mechanism of Action and Role in Different Biological and Pathological Processes",slug:"long-non-coding-rnas-biogenesis-mechanism-of-action-and-role-in-different-biological-and-pathologica",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.104861",abstract:"RNA or ribonucleic acid constitutes of nucleotides, which are ribose sugars coupled to nitrogenous bases and phosphate groups. Nitrogenous bases include adenine, guanine, cytosine and uracil. Messenger RNA, ribosomal RNA and Transfer RNA are three main types of RNA that are involved in protein synthesis. Apart from its primary role in synthesis of protein, RNA comes in variety of forms like snRNA, miRNA, siRNA, antisense RNA, LncRNA etc., that are involved in DNA replication, post-transcriptional modification, and gene regulation etc. LncRNAs regulate gene expression by various ways including at, transcriptional, post-transcriptional, translational, post-translational and epigenetic levels by interacting principally with mRNA, DNA, protein, and miRNA. Among other biological functions, they are involved in chromatin remodelling, transcriptional interference, transcriptional activation, mRNA translation and RNA processing. In this chapter we shall be discussing the origin of lncRNAs, their biogenesis, their mechanism of action and their role in many biological and pathological processes like epigenetics, genome imprinting, several cancers and autoimmune diseases.",book:{id:"11353",title:"Recent Advances in Non-Coding RNAs",coverURL:"https://cdn.intechopen.com/books/images_new/11353.jpg"},signatures:"Ishteyaq Majeed Shah, Mashooq Ahmad Dar, Kaiser Ahmad Bhat, Tashook Ahmad Dar, Fayaz Ahmad and Syed Mudasir Ahmad"},{id:"81796",title:"Apoptosis-Related Diseases and Peroxisomes",slug:"apoptosis-related-diseases-and-peroxisomes",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.105052",abstract:"Apoptosis is a highly regulated cell death program that can be mediated by death receptors in the plasma membrane, as well as the mitochondria and the endoplasmic reticulum. Apoptosis plays a key role in the pathogenesis of a variety of human diseases. Peroxisomes are membrane-bound organelles occurring in the cytoplasm of eukaryotic cells. Peroxisomes engage in a functional interplay with mitochondria. They cooperate with each other to maintain the balance of reactive oxygen species homeostasis in cells. Given the key role of mitochondria in the regulation of apoptosis, there could also be an important relationship between peroxisomes and the apoptotic process. Peroxisome dysfunction severely affects mitochondrial metabolism, cellular morphological stability, and biosynthesis, and thus contributes directly or indirectly to a number of apoptosis-related diseases. This chapter provides an overview of the concept, characteristics, inducing factors, and molecular mechanisms of apoptosis, as well as evidence for apoptosis in cancer, cardiovascular diseases, and neurodegenerative disorders, and discusses the important role of the peroxisome in the apoptosis-associated diseases.",book:{id:"10837",title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg"},signatures:"Meimei Wang, Yakun Liu, Ni Chen, Juan Wang and Ye Zhao"},{id:"81738",title:"How Do Extraction Methods and Biotechnology Influence Our Understanding and Usages of Ginsenosides?: A Critical View and Perspectives",slug:"how-do-extraction-methods-and-biotechnology-influence-our-understanding-and-usages-of-ginsenosides-a",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.103863",abstract:"Ginseng saponins, aka ginsenosides, are bioactive phytochemicals from Panax species. Panax comes from the Greek word “panakos,” which means “cure-all.” Owing to their involvement in the creation of numerous medications and nutritional supplements, ginseng saponins play an essential part, especially in the pharmaceutical sector. The main ginsenosides (i.e., Rb1, Rb2, Rc, Rd and Rf) are extracted using a variety of extraction methods, although from a limited number of Panax species. However, more than ca 1000 unique ginsenosides and 18 Panax species have been reported so far, thus demonstrating our present challenge in better understanding of the potential medicinal uses of these compounds. Moreover, ginsenoside production and extraction methods are both time-consuming and inefficient, which has stimulated the development of several efficient extraction and biotechnological technologies to speed up these processes. In this chapter, we highlighted the need to expand the cutting-edge research approaches involving these unique ginsenosides to better understand their biological activities and discover new bioactive ginsenosides as well. The main objective of this chapter is to discuss the undiscovered aspects and limitations of the current biotechnological and extraction technologies, eventually to provide a platform for the production of these unique ginsenosides.",book:{id:"10539",title:"Ginseng - Modern Aspects of the Famed Traditional Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/10539.jpg"},signatures:"Christophe Hano, Duangjai Tungmunnithum, Samantha Drouet, Mohamed Addi, Saikat Gantait and Jen-Tsung Chen"},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.103935",abstract:"Literature data demonstrate already that the presence of adenine nucleotides in the extracellular environment induces cell death that leads to several retinopathies. As said, the objective is to carry out a systematized review of the last decade, relating purinergic signaling to the outcome of cell death and retinopathies. It is possible to identify different mechanisms that occur through the activation of purinergic receptors. The exacerbated activation of the P2X7 receptor is mainly involved in the apoptotic death pathway, and this response is due to the dysregulation of some components in the intracellular environment, such as the Ca2+ ion, CD40, MiR-187, and influence of mononuclear macrophages. The A2A receptor is involved in increasing levels of cytokines and promoting inflammatory processes. The data presented can be used as a basis to better understand the mechanisms of death in retinopathies, in addition to proposing therapeutic strategies with the potential to be transposed to several other models.",book:{id:"10801",title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg"},signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira"}],onlineFirstChaptersTotal:96},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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