\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"5841",leadTitle:null,fullTitle:"Chlorophyll",title:"Chlorophyll",subtitle:null,reviewType:"peer-reviewed",abstract:"Chlorophyll presents an authoritative and comprehensive overview of the biology, biochemistry and chemistry of chlorophylls in photosynthetic organisms. Divided into seven discreet parts, the book covers topics on basic science and applied technology of chlorophyll molecules. Chlorophyll provides an insight into future developments in each field and extensive bibliography. It will be an essential resource for researchers and academic and industry professionals in the natural pigment field.",isbn:"978-953-51-3108-3",printIsbn:"978-953-51-3107-6",pdfIsbn:"978-953-51-4843-2",doi:"10.5772/65594",price:119,priceEur:129,priceUsd:155,slug:"chlorophyll",numberOfPages:132,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"7acaad1163902b52fa8ed4bb78902645",bookSignature:"Eduardo Jacob-Lopes, Leila Queiroz Zepka and Maria Isabel Queiroz",publishedDate:"May 10th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5841.jpg",numberOfDownloads:14560,numberOfWosCitations:46,numberOfCrossrefCitations:31,numberOfCrossrefCitationsByBook:4,numberOfDimensionsCitations:74,numberOfDimensionsCitationsByBook:4,hasAltmetrics:1,numberOfTotalCitations:151,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 11th 2016",dateEndSecondStepPublish:"November 1st 2016",dateEndThirdStepPublish:"January 28th 2017",dateEndFourthStepPublish:"April 28th 2017",dateEndFifthStepPublish:"June 27th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"171980",title:"Dr.",name:"Eduardo",middleName:null,surname:"Jacob-Lopes",slug:"eduardo-jacob-lopes",fullName:"Eduardo Jacob-Lopes",profilePictureURL:"https://mts.intechopen.com/storage/users/171980/images/system/171980.jfif",biography:"Prof. Dr. Eduardo Jacob-Lopes is currently an associate professor at the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. He has more than fifteen years of teaching and research experience. He has coordinated and is coordinating more than fifty research projects and/or technological developments financed by public funding agencies and private initiatives. He has published more than 600 scientific publications/communications, including 15 books, 60 book chapters, 120 original research papers, 400 research communications in national and international conferences, and 13 patents. He is a member of the editorial board of ten journals and acts as a reviewer for several national and international journals. His research interests include bioprocess engineering and sustainable engineering with an emphasis on microalgal biotechnology.",institutionString:"Federal University of Santa Maria",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"Universidade Federal de Santa Maria",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. Her research interests include microalgal biotechnology with an emphasis on microalgae-based products.",institutionString:"Universidade Federal de Santa Maria",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Universidade Federal de Santa Maria",institutionURL:null,country:{name:"Brazil"}}},coeditorTwo:{id:"171982",title:"Prof.",name:"Maria Isabel",middleName:null,surname:"Queiroz",slug:"maria-isabel-queiroz",fullName:"Maria Isabel Queiroz",profilePictureURL:"https://mts.intechopen.com/storage/users/171982/images/5563_n.jpg",biography:"Prof. Maria Isabel Queiroz is currently senior professor at the Department of Chemistry and Food, Federal University of Rio Grande. She graduated in oceanography at Federal University of Rio Grande, with a Masters in Food Technology in State University of Campinas and a doctorate in Biotechnology from Federal University of Pelotas. She has more than 30 years of teaching and research experience. She is a technical and scientific consultant of several companies, agencies and scientific journals. She has more of 500 publications/communications which include 7 books, 7 book chapters, 100 original research papers, 350 research communications in international and national conferences. Her research interest includes microalgal biotechnology with emphasis on bioprocesses.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"353",title:"Agrotechnology",slug:"agrotechnology"}],chapters:[{id:"54559",title:"Introductory Chapter: Chlorophyll Molecules and Their Technological Relevance",doi:"10.5772/67953",slug:"introductory-chapter-chlorophyll-molecules-and-their-technological-relevance",totalDownloads:1657,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:null,signatures:"Maria Isabel Queiroz, Andrêssa Silva Fernandes, Mariany Costa\nDeprá, Eduardo Jacob-Lopes and Leila Queiroz Zepka",downloadPdfUrl:"/chapter/pdf-download/54559",previewPdfUrl:"/chapter/pdf-preview/54559",authors:[{id:"171980",title:"Dr.",name:"Eduardo",surname:"Jacob-Lopes",slug:"eduardo-jacob-lopes",fullName:"Eduardo Jacob-Lopes"},{id:"261969",title:"Dr.",name:"Leila",surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka"},{id:"200454",title:"Dr.",name:"Andrêssa",surname:"Fernandes",slug:"andressa-fernandes",fullName:"Andrêssa Fernandes"},{id:"200455",title:"Dr.",name:"Mariany",surname:"Deprá",slug:"mariany-depra",fullName:"Mariany Deprá"},{id:"200457",title:"Prof.",name:"Maria Isabel",surname:"Queiroz",slug:"maria-isabel-queiroz",fullName:"Maria Isabel Queiroz"}],corrections:null},{id:"54801",title:"Chlorophyll-a and the Supply Side Ecology: Lessons from the Rocky Shores",doi:"10.5772/68044",slug:"chlorophyll-a-and-the-supply-side-ecology-lessons-from-the-rocky-shores",totalDownloads:1309,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The aims of this study were to summarize and describe the influences of phytoplankton on the larval cycle of rocky shore invertebrates, and to assess the relationship between fluctuations in chlorophyll-a concentration and the rates of larval processes. We carried out a mini review of the published data regarding the theme of the chapter, in which we described the ecological trends for the most common taxa and key species at small and larger spatiotemporal scales. The following topics were addressed: (i) the influence of phytoplankton on larval development, rhythms of larval release, larval quality, larval transport, settlement, and recruitment; (ii) the relationships between variations in chlorophyll-a concentration and the rates of larval processes; (iii) climate change on phytoplankton larva dynamics. The information presented here highlights the role of phytoplankton on rocky shore communities, as well as the importance of chlorophyll-a as a tool for modeling and forecasting the supply side ecology in rocky shore communities.",signatures:"Ana Carolina de Azevedo Mazzuco and Paula Kasten",downloadPdfUrl:"/chapter/pdf-download/54801",previewPdfUrl:"/chapter/pdf-preview/54801",authors:[{id:"198411",title:"Dr.",name:"Ana Carolina",surname:"Mazzuco",slug:"ana-carolina-mazzuco",fullName:"Ana Carolina Mazzuco"},{id:"200205",title:"Dr.",name:"Paula",surname:"Kasten",slug:"paula-kasten",fullName:"Paula Kasten"}],corrections:null},{id:"54493",title:"How Does Chloroplast Protect Chlorophyll Against Excessive Light?",doi:"10.5772/67887",slug:"how-does-chloroplast-protect-chlorophyll-against-excessive-light-",totalDownloads:2194,totalCrossrefCites:8,totalDimensionsCites:23,hasAltmetrics:0,abstract:"Chlorophylls (Chls) are the most abundant plant pigments on Earth. Chls are located in the membrane of thylakoids where they constitute the two photosystems (PSII and PSI) of terrestrial plants, responsible for both light absorption and transduction of chemical energy via photosynthesis. The high efficiency of photosystems in terms of light absorption correlates with the need to protect themselves against absorption of excess light, a process that leads to the so-called photoinhibition. Dynamic photoinhibition consists of the downregulation of photosynthesis quantum yield and a series of photo-protective mechanisms aimed to reduce the amount of light reaching the chloroplast and/or to counteract the production of reactive oxygen species (ROS) that can be grouped in: (i) the first line of chloroplast defence: non-photochemical quenching (NPQ), that is, the dissipation of excess excitation light as heat, a process that takes place in the external antennae of PSII and in which other pigments, that is carotenoids, are directly involved; (ii) the second line of defence: enzymatic antioxidant and antioxidant molecules that scavenge the generated ROS; alternative electron transport (cyclic electron transport, pseudo-cyclic electron flow, chlororespiration and water-water cycle) can efficiently prevent the over-reduction of electron flow, and reduced ferredoxin (Fd) plays a key role in this context.",signatures:"Lucia Guidi, Massimiliano Tattini and Marco Landi",downloadPdfUrl:"/chapter/pdf-download/54493",previewPdfUrl:"/chapter/pdf-preview/54493",authors:[{id:"198635",title:"Prof.",name:"Lucia",surname:"Guidi",slug:"lucia-guidi",fullName:"Lucia Guidi"},{id:"199774",title:"Dr.",name:"Massimiliano",surname:"Tattini",slug:"massimiliano-tattini",fullName:"Massimiliano Tattini"},{id:"199775",title:"Dr.",name:"Marco",surname:"Landi",slug:"marco-landi",fullName:"Marco Landi"}],corrections:null},{id:"54681",title:"Effects on the Photosynthetic Activity of Algae after Exposure to Various Organic and Inorganic Pollutants: Review",doi:"10.5772/67991",slug:"effects-on-the-photosynthetic-activity-of-algae-after-exposure-to-various-organic-and-inorganic-poll",totalDownloads:2702,totalCrossrefCites:7,totalDimensionsCites:14,hasAltmetrics:1,abstract:"Algal studies remain necessary for risk assessment and their utility in ecotoxicology is the evaluation of lethal and sub-lethal toxic effects of potential toxicants on inhabitants of several ecosystems. Effects on algal photosynthetic apparatus caused by various chemical species have been extensively studied. The present chapter summarizes the published data concerning the toxicity of various organic and inorganic pollutants such as oils, pesticides, antifoulants and metals on photosynthesis of aquatic primary producers. Biochemical mode of action resulting in the disruption of photosynthesis depends on the chemical’s nature and the characteristics of the exposed microorganism. Observed differences in response and sensitivity by different species to the same toxicant were attributed to several algal characteristics including photosynthetic capacity, pigment type, cellular lipid and protein content, and cell size. Single species bioassays either for one chemical alone or in mixture have been well reported and tolerance of both marine and freshwater water-column phytoplaktonic species has been examined. Adequate published information on multispecies tests (communities) in laboratory and field studies exists. However, risk assessment on photosynthesis of microbenthic periphyton is inadequate, though it is essential especially for hydrophobic organic molecules. Further studies are required to evaluate the adverse effects of metabolites on aquatic microalgae.",signatures:"Andreas S. Petsas and Maria C. Vagi",downloadPdfUrl:"/chapter/pdf-download/54681",previewPdfUrl:"/chapter/pdf-preview/54681",authors:[{id:"200196",title:"Dr.",name:"Andreas",surname:"Petsas",slug:"andreas-petsas",fullName:"Andreas Petsas"},{id:"200198",title:"Dr.",name:"Maria",surname:"Vagi",slug:"maria-vagi",fullName:"Maria Vagi"}],corrections:null},{id:"54702",title:"Effects of pH and Phosphorus Concentrations on the Chlorophyll Responses of Salvia chamelaeagnea (Lamiaceae) Grown in Hydroponics",doi:"10.5772/67610",slug:"effects-of-ph-and-phosphorus-concentrations-on-the-chlorophyll-responses-of-salvia-chamelaeagnea-lam",totalDownloads:1518,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Salvia chamelaeagnea (Lamiaceae) is a slow growing water‐wise evergreen shrub originating from the western province of South Africa. It is an attractive landscape, and S. chamelaeagnea is a medicinal plant. It is important to develop enhanced cultivation protocols that could result in high yield and high‐quality medicinal materials. Chlorophyll is a fundamental part of the light‐dependent reactions of the photosynthesis process. This chapter investigates the effects of four phosphorus concentrations and three pH levels of supplied irrigated water on the production of chlorophyll A, chlorophyll B, total chlorophyll, leaf colour and the nutrient uptake of S. chamelaeagnea grown in hydroponics over an 8‐week period at the Cape Peninsula University of Technology. The treatments of pH 4, pH 6 and pH 8 at 31, 90, 150 and 210 ppm of phosphorus were received by 12 groups of plants and were replicated 10 times. The results indicated that at pH 4, P fertilization significantly (P < 0.05) induced a higher chlorophyll production of S. chamelaeagnea grown in hydroponics compared to other pH treatments (pH 8 and pH 6).",signatures:"Kerwin Lefever, Charles P. Laubscher, Patrick A. Ndakidemi and Felix\nNchu",downloadPdfUrl:"/chapter/pdf-download/54702",previewPdfUrl:"/chapter/pdf-preview/54702",authors:[{id:"200292",title:"Dr.",name:"Felix",surname:"Nchu",slug:"felix-nchu",fullName:"Felix Nchu"},{id:"200819",title:"Prof.",name:"Charles",surname:"Petrus Laubscher",slug:"charles-petrus-laubscher",fullName:"Charles Petrus Laubscher"},{id:"201292",title:"Mr.",name:"Kerwin",surname:"Lefever",slug:"kerwin-lefever",fullName:"Kerwin Lefever"},{id:"201293",title:"Prof.",name:"Patrick A.",surname:"Ndakedemi",slug:"patrick-a.-ndakedemi",fullName:"Patrick A. Ndakedemi"}],corrections:null},{id:"54510",title:"Light‐Emitting Diodes: Progress in Plant Micropropagation",doi:"10.5772/67913",slug:"light-emitting-diodes-progress-in-plant-micropropagation",totalDownloads:2201,totalCrossrefCites:3,totalDimensionsCites:13,hasAltmetrics:0,abstract:"In commercial micropropagation laboratories, the light source is one of the most important factors controlling plant morphogenesis and metabolism of plant cells and tissue and organ cultures. Lamp manufacturers have begun to rate lamps specifically for plant needs. The traditional light source used for in vitro propagation is fluorescent lamps (FLs). However, power consumption in FL use is expensive and produces a wide range of wavelengths (350–750 nm) unnecessary for plant development. Light‐emitting diodes (LEDs) have recently emerged as an alternative for commercial micropropagation. The flexibility of matching LED wavelengths to plant photoreceptors may provide more optimal production, influencing plant morphology and chlorophyll content. Although previous reports have confirmed physiological effects of LED light quality on morphogenesis and growth of several plantlets in vitro, these study results showed that LED light is more suitable for plant morphogenesis and growth than FLs. However, the responses vary according to plant species. This chapter describes the applications and benefits of LED lamps on chlorophyll in plant micropropagation. Two study cases are exposed, Anthurium (Anthurium andreanum) and moth orchids (Phalaenopsisis sp.), both species with economic importance as ornamental plants, where LEDs have a positive effect on in vitro development and chlorophyll content.",signatures:"Jericó J. Bello‐Bello, Juan A. Pérez‐Sato, Carlos A. Cruz‐Cruz and\nEduardo Martínez‐Estrada",downloadPdfUrl:"/chapter/pdf-download/54510",previewPdfUrl:"/chapter/pdf-preview/54510",authors:[{id:"197218",title:"Dr.",name:"Jericó Jabín",surname:"Bello Bello",slug:"jerico-jabin-bello-bello",fullName:"Jericó Jabín Bello Bello"},{id:"197368",title:"MSc.",name:"Eduardo",surname:"Martínez Estrada",slug:"eduardo-martinez-estrada",fullName:"Eduardo Martínez Estrada"},{id:"197369",title:"Dr.",name:"Carlos Alberto",surname:"Cruz Cruz",slug:"carlos-alberto-cruz-cruz",fullName:"Carlos Alberto Cruz Cruz"},{id:"205358",title:"Dr.",name:"Juan Antonio",surname:"Pérez-Sato",slug:"juan-antonio-perez-sato",fullName:"Juan Antonio Pérez-Sato"}],corrections:null},{id:"54601",title:"Chlorophyll as Photosensitizer in Dye-Sensitized Solar Cells",doi:"10.5772/67955",slug:"chlorophyll-as-photosensitizer-in-dye-sensitized-solar-cells",totalDownloads:2979,totalCrossrefCites:10,totalDimensionsCites:18,hasAltmetrics:0,abstract:"Chlorophyll, being the most abundant pigment that commonly found in plants, bacteria, bryophytes and algae, plays a vital role in photosynthesis. Chlorophylls are natural pigments and therefore safe, environmental friendly, easily available and cheap. Chlorophyll has been experimented to function as a photosensitizer in dye-sensitized solar cells (DSSCs) as DSSCs mimic the photosynthesis process in green plants. DSSC was first developed by Gratzel in 1991 and since then has gained tremendous attention as its fabrication is cheap and easy. A DSSC basically comprises a semiconductor that has been soaked in sensitizing dye (chlorophyll), a counter electrode, and an electrolyte containing a redox mediator. The dye absorbs light, which is transformed into electricity. Chlorophyll can be extracted from the leaves of pomegranate, bougainvillea, papaya, Pandanus amaryllifolius, spinach, green grasses, seaweeds, algae and bryophytes. Chlorophyll from these sources has been studied as possible photosensitizers for DSSCs. Most researches done in chlorophyll DSSC use the extracted natural pigments. The type of solvent and pH of the dye solution will also affect the stability of chlorophyll and subsequently the performance of the DSSCs. This chapter will present an inexhaustive overview on DSSCs using chlorophyll as dye.",signatures:"Abdul Kariem Arof and Teo Li Ping",downloadPdfUrl:"/chapter/pdf-download/54601",previewPdfUrl:"/chapter/pdf-preview/54601",authors:[{id:"186084",title:"Dr.",name:"Abdul Kariem",surname:"Arof",slug:"abdul-kariem-arof",fullName:"Abdul Kariem Arof"},{id:"199862",title:"Dr.",name:"L.P.",surname:"Teo",slug:"l.p.-teo",fullName:"L.P. 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In healthy adult blood vessels, these cells proliferate at a very low rate, exhibit very low synthetic and migratory activity and express a unique repertoire of contractile proteins, ion channels, and signalling molecules required for the cell\'s contractile function. VSMC undergo significant phenotypic modulation following vascular injuries including hypoxia, oxidative stress and mechanical injury. This phenotypic transition is mainly characterized by the loss of contractility and the acquisition of a proliferative, migratory and synthetic phenotype. These drastic phenotypic alterations allow VSMCs to migrate from the media to the intima of the arterial wall where they proliferate and secrete an extracellular matrix and pro-inflammatory molecules. This phenotypic transition, also called the trans-differentiation process, plays a critical role in pathological vascular remodellings such as atherosclerosis, post-angioplasty restenosis, bypass vein graft failure, and cardiac allograft vasculopathy [1,2]. Hypoxia, mechanical stress and oxidative stress can induce VSMC trans-differentiation directly or indirectly by stimulating the release of pro-inflammatory molecules and growth factors from endothelium, macrophages, T lymphocytes or VSMC themselves. Signalling pathways involved in VSMC trans-differentiation are diverse. Among them, the 3’-5’-cyclic adenosine monophosphate (cAMP) signalling pathway stands out since cAMP is not only described to play important roles both in differentiated and transdifferentiated VSMCs, but can also have opposite effects in VSMCs with the same phenotype. Indeed, in trans-differentiated VSMCs, cAMP has dual opposite effects on migration and inflammation and stops cell proliferation. Alternatively, in differentiated VSMCs, cAMP induces relaxation, expression of contractile proteins, maintenance of a low proliferation rate and can stimulate or inhibit apoptosis (Figure 1). The diversity of cAMP effects in VSMC (and in cells in general), is due to the ability of this second messenger to transduce extracellular signals in a compartmentalized manner, allowing individual stimuli to produce distinct pools of cAMP localized in discrete subcellular regions. These pools of cAMP are produced near a subset of cAMP effectors, themselves located near their substrates and engage specific cell responses according to the cellular context [3]. Adenylyl cyclases (AC), phosphodiesterases (PDE) and the scaffolding proteins A kinase anchored proteins (AKAPs) play a determinant role in cAMP compartmentalization. Final cAMP effect depends on which isoforms of these proteins are expressed. During the VSMC trans-differentiation process, important changes in the expressions of such proteins occur, allowing a re-organization of the cAMP signalling compartmentalization, therefore giving VSMC the ability to acquire properties specific to the trans-differentiated state. After a presentation of the cAMP signalling pathway, this chapter discusses data demonstrating the diversity of roles of cAMP in differentiated and transdifferentiated VSMCs.
Roles of cAMP (3’-5’ adenosine monophosphate) in differenciated and trans-differentiated vascular smooth muscle cells (VSMC); AC8: adenylyl cyclase 8.
The c-AMP signalling pathway begins with the release of cAMP into the cell which is mostly initiated by the activation of G-protein coupled receptors (GPCRs) by several different hormones and neurotransmitters. The ligand-bound GPCR catalyzes the exchange of GDP for GTP on the α-subunit of the coupled heterotrimeric G protein, which results in the activation of the α-subunit and its dissociation from the βγ dimer. Both the α and the βγ subunits can then activate or inhibit distinct intracellular signalling cascades. The αs of the Gs subtype activates adenylyl cyclases (AC) witch catalyzes the synthesis of cAMP from ATP. Increased levels of cAMP are translated into cellular responses by cAMP effectors. The best known is the c-AMP dependant protein kinase A (PKA), but also include cyclic-nucleotide gated ion channels (CNGCs) and the recently discovered Rap1-guanine nucleotide exchange factor (Epac), three effectors known to mediate a multitude of cAMP signalling pathways. (Figure 2). The end of cAMP signalling is achieved by its decomposition into AMP catalyzed by phosphodiesterases (PDEs) and its active efflux through transporters of the multidrug resistance-assocuated protein (MRP) family [4,5]. One particularity of the cAMP signalling pathway is its high degree of compartmentalization. Multiprotein complexes organize the location of the different cAMP effectors to specific subcellular locations and allow cAMP to propagate a plethora of cell responses in a spatio-temporal manner [3]. These multiprotein complexes are at the foundation of cAMP compartmentalization, they involve AC, the scaffolding proteins AKAPs and PDEs.
Cyclic adenosine 3’, 5’-monophosphate (cAMP) is produced from ATP by adenylyl cyclase (AC) upon activation of Gs-protein coupled receptors. The local concentration and distribution of cAMP gradients is limited by phosphodiesterases (PDE) which generate localized pools of cAMP throughout the cell. The increase in cAMP is translated to cellular responses by the cAMP effectors protein kinase A (PKA), EPAC (exchange protein activated by cAMP) and cyclic nucleotide -gated ion channels (CNGCs). A kinase anchored proteins (AKAPs) target cAMP effectors to distinct cell compartments. They also intract with AC, PDE, cAMP effectors substrates and further scaffolding proteins, providing spatial and temporal specificity of the cAMP pathway.
In mammals, cAMP is synthesized from ATP by members of the Class-III AC (Adenylyl Cyclase)/ADCY family (E.C 4.6.1.1) Adenylyl cyclases (ACs) are currently grouped in six classes based on their primary amino acid sequences. Class I ACs have been found exclusively in γ -proteobacteria. Class II ACs are toxins secreted by Bacillus anthracis, Bordetella pertussis and Pseudomonas aeruginosa. Only few members of class IV, V and VI ACs have been described to date and consists in bacterial enzymes. Class III ACs is universal. Class III ACs is found in metazoa, protozoa, fungi, eubacteria, some archaebacteria and certain green algae. Neither class III ACs nor any other type of AC has ever been conclusively identified in higher plants (Embryophyta).
Beyond their synthase activity, ACs can function as scaffolds, and therefore contribute to the cAMP signalling compartmentalization. Indeed, several works have shown that specific AC isoforms have the capacity to interact with several proteins/enzymes on their N-terminus allowing an isoform selective coupling with specific downstream signalling cascades [11,12]. AC isoforms are themselves confined in several structural specific cellular compartments. The best characterized is their association with caveolar, lipid-rafts and the anchoring proteins AKAP [13,14]. Selective adenylyl cyclase isoform localization, regulation and coupling with specific downstream targets provide adenylyl cyclase isoform-selective patterns of signalling, that links specific AC isoforms to distinct cell processes [15,16]. For example, alteration of the AC population expressed in DDT1-MF2 cells (derived from hamster vas deferens smooth muscle) changes the processing of stimulatory and inhibitory input [17] and differential expression of AC isoforms in two VSMC models account for opposite effect of isoprenaline on cAMP production [18].
Differentiated VSMC have been shown to express different isoforms of AC [18,19]. AC3-5-6 are clearly the most highly expressed isoenzymes in VSMCs, while Type 8 AC (AC8) is undetectable in differentiated VSMCs and is strongly induced in trans-differentiated VSMC [20,21].
Phosphodiesterases (PDE) comprise a large superfamily of enzymes; 11 families (PDE1-PDE11) have been characterized on the basis of their amino acid sequences, substrate specificity, allosteric regulatory characteristics and pharmacological properties [22,23]. In total, the superfamily of PDEs encompasses 25 genes in mammals giving rise to 200 reported distinct gene products corresponding to different splice variants that are often expressed in a tissue-specific manner. The substrate specificity of PDEs includes cAMP-specific, cGMP specific, and dual-specific PDE. PDE 4-7-8 are highly specific for the hydroysis of cAMP, PDE5, 6, 9 are cGMP specific and PDE1, -2, -3, -10, -11 hydrolyse both cAMP and cGMP. There are four major PDE families found in VSMCs: PDE1, PDE3, and PDE4 PDE5 [24]. PDE3 and PDE4 have been shown to account for the majority of cAMP hydrolysis, whereas PDE1 and PDE5 are mainly responsible for cGMP-hydrolysis [25,26]. PDE1A and -1B, are expressed in differentiated VSMC. PDE1A has the particularity to be localized in different cell compartments according to the VSMC phenotype; it is predominantly cytoplasmic in medial contractile VSMC and becomes nuclear in neointimal synthetic VSMC [27]. PDE1C is specifically induced in trans-differentiated VSMC [28]. PDE3A, the main isoform expressed in arterial tissue, platelets and cardiac tissue is found is VSMCs as well as PDE3B. The largest PDE family to date, the cAMP specific PDE4 family, is expressed in numerous tissues, notably in vascular tissue. Four genes (PDE4A/B/C/D) encode over 20 distinct PDE4 isoforms as a result of mRNA splicing and the use of distinct promoters [29]. It was reported that two PDE4 “long forms”, PDE4D3 and PDE4D5 are expressed in rat and human VSMC [30,31] and that the two “short forms” PDE4D1 and PDE4D2 are specifically expressed in trans-differentiated VSMC [32]. PDE5A is the major cGMP hydrolyzing PDE expressed in arterial tissues[33,34].
The first intracellular target of cAMP identified is the well characterized PKA holoenzyme. cAMP-PKA-mediated signalling is known to affect numerous intracellular targets in response to a wide variety of molecular signals. Numerous studies over the past 40 years have identified hundreds of PKA substrates in the plasma membrane, nucleus, and cytoplasm of cells. The PKA holoenzyme is a tetramere consisting of two catalytic subunits (C) that are maintained in an inactive conformation by a regulatory (R) subunit dimer [35]. Binding of two cAMP molecules on each R subunit leads to a conformational change and dissociation of two catalycally active C monomers, which phosphorylate serine and threonine residues on specific substrate proteins. Molecular cloning identified 4 R subunits and 4 C subunits called respectively RIα, RIβ, RIIα, RΙΙβ, Cα, Cβ, Cγ, and PRKX (the human X chromosome-encoded protein kinase X, a cAMP dependent kinase that forms a catalytically inactive holoenzyme only with the RI subunit). The R subunits exhibit different cAMP binding affinities and can form both homo and heterodimers leading to a large number of combinations. The subcellular localization of PKA is determined by PKA binding to A kinase ankoring proteins, AKAPs. AKAPs act as scaffolds which give PKA access to substrates localized in specific compartments within the cell and participate to cAMP signalling compartmentalization as depicted below [36,37].
Epac proteins are the most recent addition to the group of cAMP signalling effectors. Their discovery explains various effects of cAMP that could not be attributed to the established targets PKA and CNGs. Epac was identified in a database screen conducted to explain the independent activation of the small G protein Rap by cAMP [38]. At the same time, a screen for proteins containing cyclic-nucleotide-binding domains revealed the presence of two isoforms of Epac, Epac1 and Epac2 [39]. Epac proteins function as guanine nucleotide exchange factors (GEFs) both for Rap1 and Rap2. Rap1 and rap2 proteins belong to the Ras family of small G proteins, which cycle between an inactive GDP-bound state and an active GTP-bound state. The GTP-bound Rap mediates signalling by associating with and activating effector proteins. GEFs catalyze the exchange of GDP for GTP and thereby the activation of the small G protein (Figure 3). Herein, Epac1 and Epac2 proteins are also called cAMP-GEF I and II respectively. Their subcellular localizations are determined, like PKA, by binding to AKAPs. Epac1 and Epac2 are present in most tissues, though with different expression levels. Epac1 is highly abundant in blood vessels, kidney, adipose tissue, central nervous system, ovary and uterus, whereas Epac2 is mostly expressed in the central nervous system, adrenal gland, and pancreas. Epac proteins are implicated in many cAMP-regulated processes such as insulin secretion, cardiac contraction, vascular permeability, cell migration, neurotransmitter release and immunity [40,41].
Cyclic nucleotide-gated (CNG) channels are non-selective cation channels first identified in retinal photoreceptors and olfactory sensory neurons. They are opened by the direct binding of cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the super-family of voltage-gated ion channels.
CNG channels consists in heterotetrameric complexes resulting from the association of two or three subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to different channels. Their activity is modulated, at least in part, by Ca2+/calmodulin and by phosphorylation. The role of CNG channels has been established in retinal photoreceptors and in olfactory sensory neurons. Mutations in CNG channel genes give rise to retinal degeneration and color blindness [42].
CNG channels are widely expressed in vascular tissues across species and vascular beds [43,44]. Specifically, CNGA1 was found to be very expressed in the endothelium layer and, with a much lower extent, in VSMC [44]. In contrast, strong expression of CNGA2 has been found in both the endothelium and media of human arteries [43]. Functionally, CNG channels play an important role in endothelium dependent vascular dilatation to a number of cAMP-elevating agents including adenosine, adrenaline and ATP [45-47]. Concerning the function of CNG in differentiated VSMC, to our knowledge, only one report demonstrates that CNG contributes to thromboxaneA2-induced contraction of rat small mesenteric arteries[48].
The Rap1 GTPases cycle between a GTP-bound (active state) and GDP- bound (inactive state). Cycling between the active and inactive states is facilitated by guanine nucleotide exchange factors (GEFs) that release GDP and allow binding of GTP, as well as GTPase activation proteins (GAPs) wich accelerate GTP hydrolysis.
The idea of compartimentalized pools of cAMP originated in 1979 when Brunton et al. showed that while both the β-adrenergic receptor agonist isoprotrenol and prostaglandin E1 increased cAMP concentration in perfused rat hearts, only isoproterenol increased glycogen metabolism and phosphorylation of troponin [49]. These results illustrated the fact that different hormones may act through the same messenger to generate different pools of cAMP and mediate distinct physiological responses. An increasing number of results support now the existence of distinct cAMP microdomains that control cAMP signalling. ACs, PDEs and the scaffolding proteins AKAPs are at the foundation of this cAMP signalling compartmentalization [50,51]. As mentioned, -ACs can orchestrate their own microenvironment by recruiting a variety of signalling and scaffolding molecules, - PDEs mediate local cAMP degradation and literally sculpt gradients of cAMP surrounding specific signalling complexes and therefore regulate the availability of cAMP/cGMP to their effectors –AKAPs dynamically assemble the three different cAMP effectors to control the cellular actions of cAMP [37]. As their name implies, AKAPs were originally described to target PKA to distinct subcellular locations and confine activation to only a subset of potential targets. In reality, these proteins have the ability to form complexes with other signalling molecules including Epac proteins, protein kinases, phosphatases, phosphodiesterases, AC, as well as GPCR and ion channels. AKAPs are localized to numerous cellular sites, including the plasma membrane, Golgi, centrosome, nucleus, mitchondria and cytosol. The first AKAP to be characterized was microtubule associated protein-2 (MAP2), initially identified because of it co-purified with RII from brain extract [52]. The AKAP family has grown and includes more than 50 structurally diverse, but functionally similar members. Despite their diversity, AKAP orthologues have been identified in a range of species, including yeast, nematodes, mice and humans. All AKAPs share common properties: 1) they contain a PKA-anchoring domain 2) compartmentalization of individual AKAP-PKA units occur through specialized targeting domains that are present on each anchoring protein 3) they have the ability to form complexes with other signalling molecules including protein kinases, phosphatases, phosphodiesterases, AC, as well as GPCR and ion channels 4) AKAPs are recruited into much larger multiprotein complexes through the interactions with other adaptator molecules such as PDZ and SH3 domain containing proteins. These four properties of AKAPs allow these proteins to integrate multiple signalling pathways, allowing the convergence of signals to a common target [36,37].
Elevation of intracellular cAMP after activation of Gs coupled receptors by vasorelaxing hormones such as adrenaline, noradrenaline and the endothelium-derived prostaglandine I2 (PGI2) induces a rapid and efficient relaxation of mature differentiated SMCs [53]. Moreover, the cAMP elevating agent forskolin induces a relaxant effect in VSMCs
A cause to effect relationship between the decreased expression of some specific components of the cAMP signalling and proliferative capacity of VSMC has been demonstrated. Inversely, emergence of PDEs in trans-differentiated VSMC allows them to proliferate.
The cAMP Response Element Binding Protein (CREB) is a transcription factor, well known to be phosphorylated and activated by PKA. CREB expression has been shown to be dramatically decreased in cultured trans-differentiated VSMCs and in the media of numerous rodent and porcine models of vascular diseases. Depletion of this transcription factor
AKAP12β, a member of the AKAP family, is markedly decreased in human and rodent vascular lesions. Overexpression of AKAP12 β attenuates serum-induced SMC growth in
PDE1C, a PDE isoform hydrolyzing both cAMP and cGMP, is expressed in proliferating human VSMCs but is absent in quiescent cells. In
As mentioned above, CREB depletion elicits changes consistent with those observed in SMCs from pathologically remodelled arteries
Some studies demonstrate that cAMP is pro-apoptotic in SMCs whereas others present cAMP as an anti-apoptotic factor in these cells. The opposite effect of cAMP on apoptosis in the same type cell can be explained by the compartmentalization of cAMP signalling since these studies use different ways to elevate intracellular cAMP. Some studies use cAMP elevating agents, whereas others use hormones such as prostacyclin. In aortic VSMC, Torella et al. show that cAMP analogs inhibits apoptosis through Ser83 phosphorylation of p85αPI3K [77]. Additionally, in the same model, the AC activator forskolin reduces apoptosis in serum-deprived rat aortic VSMC at a site upstream of caspase 3 via activation of PKA [78]. In line with these studies, inhibition of CREB function in aortic VSMC induces apoptosis of rat aortic VSMC, possibly through downregulation of bcl2 expression [79]. Adversely, cAMP elevation in response to prostacyclin induces apoptosis in rat aortic VSMC through the inhibition of extracellular signal-regulated kinase activity [80].
cAMP is well known to diminish cell growth and to promote cell-differentiation in general, it can even be antagonistic to the effect of growth factors [81]. The first clue that cAMP might have a role in controlling growth of cultured cells emerged from two studies. Burk observed that two drug inhibitors of cAMP phosphodiesterase activity, caffeine and theophylline, slowed the growth of normal and transformed baby hamster kidney (BHK) cells [82]. At the same time, Ryan and Heidrick reported that cAMP itself inhibited the growth of Hela cells [83]. The first demonstration that cAMP inhibits proliferation of VSMCs was done by Southgate and Newby showing the inhibitory effect of 8-Br-CAMP on serum-induced proliferation of rabbit aortic smooth muscle cells [84]. This inhibitory effect of cAMP on VSMC growth was confirmed
A growing body of evidence emerged in the beginning of the 1990’s implicating cAMP in the inhibition of trans-differentiated VSMC migration. These studies, using analogs of cAMP, activators of ACs and cAMP raising agents in VSMCs, have demonstrated that an increase in cAMP positively correlates with the inhibition of VSMC migration. Indeed, raising the intracellular concentration of cAMP either with dopamine, acting throught D1 receptors, adrenomedullin, or forskolin, inhibited migration of VSMCs stimulated with PDGF or serum [102-104]. Studies in rat aortic SMCs suggest that vasoactive agents that elevate intracellular cAMP inhibit cell movement by disassembling actin stress fibers of the cytoskeleton [105,106]. Furthermore, downregulation of PKA abrogates inhibition of VSMC chemotaxis by forskolin [89]. The inhibitory effect of cAMP on VSMC migration is re-inforced by the fact that inhibiting all together PDE3 and PDE4D, the two main PDE isoforms expressed in VSMCs that account for cAMP hydrolysis in VSMC [26,30,107] markedly potentiated both the anti-migratory effect and the increase in cAMP caused by forskolin and significantly inhibited PDGF-induced VSMC proliferation and migration [90,108,109]. In addition, Newman et al demonstrated that forskolin inhibits TNFα-induced interleukin 6 expression and migration in human vascular smooth muscle cells [110]. This effect could involve the transcription factor CREB since PDGF-induced migration was decreased by active CREB and augmented with dominant negative CREB [66,95] ; In addition, a negative correlation has been described between the CREB level and the PDGF-activated SMC migration [64]. Nonetheless, the role of CREB in SMC migration remains unclear since CREB has been demonstrated to be involved in UTP, arachidonic acid and TNF alpha-induced SMC migration of VSMCs [111,112]. Moreover, recent studies show that oxidized and non-oxidized fatty acids induce SMC motility through this transcription factor [113,114].
By demonstrating that differential expression of ACs isoforms in two VSMC models account for opposite effects of isoprenaline on cAMP production in VSMC, Webb and co-workers suggested for the first time that changes of AC isoform(s) expression in VSMCs could account for the manifestation of vascular diseases [18]. In line with this study, Limon’s group recently demonstrated that the emergence of the calcium/calmodulin positively regulated AC isoform 8 (AC8) in trans-differentiated VSMCs is involved in VSMC migration. Type 8 AC is barely undetectable in differentiated VSMCs and is strongly induced in trans-differentiated VSMCs. A causal relationship between AC8 apparition and the migratory capacities of VSMCs has been established. Indeed, authors show that 10 days after balloon angioplasty Balloon angioplasty in rat carotid artery serves as an in vivo model of VSMC migration and proliferation.
A study from Adkins and coll. demonstrate that the elevation of intracellular cAMP by rapamycin inhibits the secretion of the pro-inflammatory molecule Tumor Necrosis Factor alpha (TNF-α) in lipopolyssacharide treated VSMCs from human saphenous vein segments [110]. Adversely, Clement and collaborators suggest that the production of cAMP specifically by AC8 is involved in the potentiator effect of prostaglandin E2 (PGE2) on the secretion of phospholipase A2 (sPLA2), a marker of inflammation, in response to interleukine 1 β (IL1β) in primary cultures of rat aortic smooth muscle cells [20]. In details, authors show that PGE2 i) induces the transition of CMLV towards a trans-differentiated/ inflammatory state through the activation of the subtype 4 Gs-linked PGE2 receptor EP4, ii) acts in synergy with IL1β to potentiate the secretion of phospholipase A2 and the disorganization of the alpha actin cytoskeleton. This potentiator effect is the result of a simultaneous activation of PGE2 receptors EP4 and EP3: in differentiated VSMC, EP3 receptors inhibit cyclase activity induced by EP4 and become activator of this activity in trans-differentiated VSMC. This switch of regulation is the result of the emergence of AC8 in IL1β−treated VSMC.
Synthetic VSMCs, in the atherosclerotic and neointimal lesions, produce an abundant exra-cellular matrix (ECM), rich in type I collagen (collagen I). This ECM plays an important role in vessel wall thickening and in the occlusion of the vessel lumen. In addition, collagen I in vascular lesions may also regulate VSMC proliferation/migration, platelet circulation, monocyte activation, lipid accumulation, calcification, and plaque stability [74]. cAMP elevating agents have been shown to inhibit collagen I synthesis induced by fetal calf serum- and TGF-β [75]. Emergence of PDE1-c in trans-differentiated SMCs from rat aortic and human saphenous vein explants opposes the inhibitory effect of cAMP on collagen 1 synthesis, and accounts, at least in part, for the increase of collagen 1 expression in trans-differentiated VSMCs. The use of specific pharmacological inhibitors and si-RNA reveal that the cAMP-mediated inhibitory effect on collagen 1 synthesis involves cyclic nucleotide gated channels but not PKA, nor Epac [76].
Depending on the relative abundance and localization of the components of the cAMP signalling pathways, cAMP effects on VSMC vary in differentiated and trans-differentiated VSMCs (Figure 4). Because trans-differentiated VSMCs play a crucial role in atherosclerosis and are solely responsible for post-angioplasty restenosis, understanding molecular mechanisms leading to VSMC trans-differentiation is crucial to develop novel therapeutic strategies. Reducing post-angioplasty restenosis which affects 20-25% of patients treated with bare metal stents, is one of the major challenges in cardiovascular medicine. At the beginning of 2000’s, the apparition of stents locally releasing anti-proliferative drugs (ie drug-eluting stents (DES), have significantly changed interventional cardiology, due to their remarkable ability to reduce restenosis compared to bare metal stents, However, their overwhelming success has quickly decreased since is limited due to an increased risk of late stent thrombosis. Poor re-endothelialization remains the major important pathologic predictor of late stent thrombosis [117], therefore, it has been suggested that DES should ideally have a selective anti-migratory and/or proliferative effect on VSMCs, without affecting, or, even better, promoting re-endothelialization [77,118]. Identifying the specific components of the cAMP pathway specifically involved in VSMC trans-differentiation may be a novel concept for the development of new drugs for DES, therefore improving the treatment of pathological vascular remodellings.
Expression of cAMP components in differentiated and trans-differentiated VSMC and consequences on VSMC functions. AC adenylyl cyclase; AKAP A-kinase anchoring proteins; Epac exchange proteins directly activated by cAMP; CREB cAMP response element binding protein; PDE phosphodiesterases.
The essence of mathematical design cannot be ignored in the analysis of real world engineering applications i.e. the research in engineering and mathematics is a two way parallel track that interrelates and coordinates towards value added research. In specific, the use of transforms in the field of electrical, electronic and communication engineering is unimaginable. In the present scenario of Covid-19 pandemic, world is looking to sustainable development of biomedical devices for critical monitoring and efficient vaccination for human survival [1, 2, 3, 4]. In general, the Fourier transform (FT) is a mathematical tool which transforms the time domain signal into a frequency domain representation used in analysis of biomedical, wireless communication, signal and image processing applications. In literature, many researchers had used this tool in frequency domain analysis of all biomedical signals like electrocardiogram (ECG), photoplethysmographic (PPG) and blood pressure (BP).
In continuation to FT, different transforms were developed to analyze and design of various applications based on the requirement [5, 6]. In general, the FT is used in analysis of stationary signals; the wavelet transform (WT) is a mathematical tool used in analysis of both stationary and non-stationary signals. Discrete wavelet transform (DWT) used in enormous application in various engineering fields.
So, in this chapter we addressed some of the research challenges in ECG and PPG signal processing using Fourier and Wavelet transforms.
Jean-Baptiste Joseph Fourier a French mathematician had developed theoretical and mathematical framework for Fourier analysis and harmonic analysis, which was laid down foundation to other transforms and important applications. Forward and inverse transform of a continuous time Fourier transform (CTFT) for a time domain signal
Here,
For ease of processing the continuous time signal is converted into discrete time, then the corresponding forward and inverse transform of a discrete Fourier transform (DFT) for a discrete time signal
Here,
Similarly, the continuous wavelet transform (CWT) is defined as
where,
Discrete WT (DWT) uses a series of low pass filters (LPF) and high pass filters (HPF) to decompose the signal of interest into different scales as approximate (
A 3-stage DWT decomposition tree is illustrated in Figure 1.
A sample of 3-stage Wavelet decomposition tree, In Matlab® ‘wavedec’ command will decompose signal of interest and gives
After first level of decomposition A1 and D1 will be the outputs, D1 will be stored in
C matrix gives the concatenated approximate and detail coefficients.
The Electrocardiogram (ECG) is an electrical manifestation of contractile activity of the heart, is a representation of instantaneous electrical activity of the heart during its contraction and relaxation over a period of time. A standard 12 leads ECG is recorded with the help of surface electrodes placed on the limbs and chest. In general, ECG is a widely accepted diagnosis tool in clinical validations of heart related diseases. Figure 2 shows a typical ECG signal, marked with all the characteristic waves and durations such as P wave, QRS complex wave, T wave and ST segment [7].
Typical recorded ECG signal in the laboratory.
Monitoring of blood oxygen saturation (SpO2) is one of the important parameter to know the health status of Covid-19 affected patient. Pulse oximeter uses sensor probes to record photoplethysmographic (PPG) signals so as to estimate the SpO2 values. Typical recorded PPG signal is shown in Figure 3.
Typical recorded PPG signal in the laboratory.
Fourier transform (FT) is used to analyze the behavior of biomedical signals in frequency domain. In Matlab FFT command can be used to get the frequency domain signal.
Following is the sample code to plot time and frequency domain signals.
Some additional modifications will be done in the program to get the following plots.
In the bottom trace of Figure 4, it can be seen that the frequency domain components of ECG signal are extending from 0 to 100 Hz, the main source of noise 60 Hz power line interference (PLI) the spike at 60 Hz can be observed. So, the complete frequency domain behavior of signal can be computed using fft command.
Recorded ECG signal in top trace and its corresponding spectrum after application of FFT in bottom trace.
Similarly, the frequency domain components of PPG signal is shown in Figure 5. It can be seen from the bottom trace that frequency components present in PPG signal are pulse rate or heart rate component and MA noise component. Likewise it can be continued for many biomedical signals to see the frequency domain behavior of the signal.
Recorded PPG signal in top trace and its corresponding spectrum after application of FFT in bottom trace.
Flowchart for de-noising of recorded signal using Fourier transform.
So, use of Fourier transform in de-noising of signal can be described as shown in Figure 6.
In general adaptive filter provide a viable solution when signal and noise are in same frequency range. Adaptive filter requires a two input signals [8].
For example, in a power line interference cancelation from ECG signal, one is recorded noisy ECG signal and other is power line noise. So, here a synthetic noise reference signal will be generated using Fourier transform which will be used as another input to the adaptive filter will potentially eliminate additional sensor for acquisition shown in Figure 7.
Flowchart for generation of synthetic noise reference signal using Fourier transform.
A synthetic noise reference signal is generated for use in adaptive filtering without using any extra hardware. It is generated from the motion corrupted signal in the following way. The frequency spectrum of MA corrupted PPG signal consists of various frequency components, the pulsatile (0.5–4 Hz), respiratory activity (0.2–0.35 Hz) and MA noise component (0.1 Hz or more) information. By setting the co-efficients of cardiac and respiratory activity frequency components in the spectrum of MA corrupted PPG to zero, a modified spectrum corresponding to noise is obtained. By applying inverse Fourier transform to this modified spectrum, a synthetic noise reference signal is generated. The corresponding adaptive filter is shown in Figure 8.
Motion artifact reduction from PPG signals using Adaptive filter.
With the help of LMS adaptive algorithm, MA noise is removed by estimating the synthetic noise reference signal and adapting the filter coefficients based on filter order. The necessary equations to implement the proposed method are given below:
where i: 0,1,2, …, L, L: filter order, S(n) + N(n): MA corrupted PPG signal,
The result of above methodology is presented in Figure 9, below. Figure 9
Recorded PPG signal in (a1), generated MA synthetic reference signal in (b1) and MA reduced PPG signal in (c1) and their corresponding spectra in (a2)-(c2) respectively.
The biomedical signals such as ECG and PPG signals are quasi periodic signals i.e. the period of the signal continuously changes with time, but it is a periodic signal. In general, the pure periodic signals are stationary in nature means its period will be constant irrespective of time. So, Fourier transform is not sufficient to analyze the quasi-periodic signals. Wavelet transform will provide a viable solution to the same [9, 10].
The general de-noising procedure follows the steps described below and shown in Figure 10.
Wavelet Denoising methodology.
There are two important steps: how to choose the threshold, and how to perform the thresholding [10]. In hard thresholding process, the elements whose absolute values are lower than the threshold will be set to zero. Soft thresholding is an extension of hard thresholding, first setting to zero the elements whose absolute values are lower than the threshold, remaining coefficients are compressed.
The same results were presented in Figures 11–13. Similar results were presented for PPG signal as shown in Figure 14.
(a) ECG signal corrupted with Electromyography signal (b) De-noised ECG signal using wavelet de-noising methodology.
(a) ECG signal corrupted with baseline noise (b) De-noised ECG signal using wavelet de-noising methodology.
(a) ECG signal corrupted with power line noise (b) De-noised ECG signal using wavelet de-noising methodology.
(a) PPG signal corrupted with MA noise (b) De-noised PPG signal using wavelet de-noising methodology.
Transforms like Fourier and wavelet transforms were used in biomedical signal analysis and processing. Fourier and wavelet transforms were utilized to reduce motion artifacts from PPG signals so as to produce correct blood oxygen saturation (SpO2) values. In an important contribution we utilized FT for generation of reference signal for adaptive filter based motion artifact reduction eliminating additional sensor for acquisition of reference signal.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Transitions to alternative transportation technologies such as electric vehicles (EVs) have gained increased attention from the automotive industries. A fuel cell electric vehicle (FCEV) occupying a hydrogen engine is one of the most stupendous technologies, since it is suitable for a large-scale transportation. However, its performance limitations are in question due to voltage degradation in long term operations through steady conditions under constant load and dynamic working conditions. Other drawbacks of using fuel cells in EVs are energy balances and management issues necessary for vehicle power and energy requirements. An efficient solution to accommodate driving behavior like dynamic loads comprises of hybridizing PEMFCs with energy storage devices like supercapacitors and batteries. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:20,paginationItems:[{id:"82526",title:"Deep Multiagent Reinforcement Learning Methods Addressing the Scalability Challenge",doi:"10.5772/intechopen.105627",signatures:"Theocharis Kravaris and George A. 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