Most common types of congenital heart defects.
\\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:"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:"10779",leadTitle:null,fullTitle:"21st Century Nanostructured Materials - Physics, Chemistry, Classification, and Emerging Applications in Industry, Biomedicine, and Agriculture",title:"21st Century Nanostructured Materials",subtitle:"Physics, Chemistry, Classification, and Emerging Applications in Industry, Biomedicine, and Agriculture",reviewType:"peer-reviewed",abstract:"Nanostructured materials (NMs) are attracting interest as low-dimensional materials in the high-tech era of the 21st century. Recently, nanomaterials have experienced breakthroughs in synthesis and industrial and biomedical applications. This book presents recent achievements related to NMs such as graphene, carbon nanotubes, plasmonic materials, metal nanowires, metal oxides, nanoparticles, metamaterials, nanofibers, and nanocomposites, along with their physical and chemical aspects. Additionally, the book discusses the potential uses of these nanomaterials in photodetectors, transistors, quantum technology, chemical sensors, energy storage, silk fibroin, composites, drug delivery, tissue engineering, and sustainable agriculture and environmental applications.",isbn:"978-1-80355-085-5",printIsbn:"978-1-80355-084-8",pdfIsbn:"978-1-80355-086-2",doi:"10.5772/intechopen.94802",price:139,priceEur:155,priceUsd:179,slug:"21st-century-nanostructured-materials-physics-chemistry-classification-and-emerging-applications-in-industry-biomedicine-and-agriculture",numberOfPages:388,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"72c67f97f9bef68200df115b5fd79884",bookSignature:"Phuong V. Pham",publishedDate:"April 20th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10779.jpg",numberOfDownloads:2305,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:2,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:3,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 24th 2021",dateEndSecondStepPublish:"July 22nd 2021",dateEndThirdStepPublish:"September 20th 2021",dateEndFourthStepPublish:"December 9th 2021",dateEndFifthStepPublish:"February 7th 2022",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"236073",title:"Dr.",name:"Phuong",middleName:"Viet",surname:"Pham",slug:"phuong-pham",fullName:"Phuong Pham",profilePictureURL:"https://mts.intechopen.com/storage/users/236073/images/system/236073.png",biography:"Phuong V. Pham is a pioneering scientist in materials science and electronic devices. He is currently a senior scientist at the School of Micro-Nano Electronics and Hangzhou Global Scientific and Technological Innovation Center (HIC), Zhejiang University, China. He earned a Ph.D. from SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University (SKKU), South Korea. Then, he spent a few years as a postdoctoral researcher and research fellow at the School of Advanced Materials Science and Engineering, SKKU and the Center for Multidimensional Carbon Materials (CMCM), Institute for Basic Science (IBS), South Korea, respectively. He is a recipient of the NSF Career Award and the National Postdoctoral Award for Excellent Young Scientists, China. His research interests include low-dimensional materials, 2D material synthesis, twistronics, straintronics, 2D heterostructures, doping technique development, nanocomposites, block copolymers, plasma engineering for flexible display, sensors, photodetectors, transistors, organic light-emitting diodes, and wearable electronics.",institutionString:"Zhejiang University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Zhejiang University",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"208",title:"Material Science",slug:"nanotechnology-and-nanomaterials-material-science"}],chapters:[{id:"79483",title:"Physics of Nanostructure Design for Infrared Detectors",doi:"10.5772/intechopen.101196",slug:"physics-of-nanostructure-design-for-infrared-detectors",totalDownloads:133,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Infrared detectors and focal plane array technologies are becoming ubiquitous in military, but are limited in the commercial sectors. The widespread commercial use of this technology is lacking because of the high cost and large size, weight and power. Most of these detectors require cryogenic cooling to minimize thermally generated dark currents, causing the size, weight, power and cost to increase significantly. Approaches using very thin detector design can minimize thermally generated dark current, but at a cost of lower absorption efficiency. There are emerging technologies in nanostructured material designs such as metasurfaces that can allow for increased photon absorption in a thin detector architecture. Ultra-thin and low-dimensional absorber materials may also provide unique engineering opportunities in detector design. This chapter discusses the physics and opportunities to increase the operating temperature using such techniques.",signatures:"Nibir Kumar Dhar, Samiran Ganguly and Srini Krishnamurthy",downloadPdfUrl:"/chapter/pdf-download/79483",previewPdfUrl:"/chapter/pdf-preview/79483",authors:[{id:"428664",title:"Prof.",name:"Nibir K.",surname:"Dhar",slug:"nibir-k.-dhar",fullName:"Nibir K. Dhar"},{id:"439626",title:"Dr.",name:"Samiran",surname:"Ganguly",slug:"samiran-ganguly",fullName:"Samiran Ganguly"},{id:"439627",title:"Dr.",name:"Srini",surname:"Krishnamurthy",slug:"srini-krishnamurthy",fullName:"Srini Krishnamurthy"}],corrections:null},{id:"79186",title:"Noise Analysis in Nanostructured Tunnel Field Devices",doi:"10.5772/intechopen.100633",slug:"noise-analysis-in-nanostructured-tunnel-field-devices",totalDownloads:52,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tunnel Field Effect Transistors (TFETs) have appeared as an alternative candidate of “beyond CMOS” due to their advantages like very low leakage current and steep sub-threshold slope i.e. <60 mV/dec., etc. From past decades, researchers explored TFETs in terms of high ON current and steep subthreshold slope at low supply voltage i.e. < VDD = 0.5 V. The reliability issues of the device have profound impact on the circuit level design for practical perspectives. Noise is one of the important parameters in terms of reliability and very few research papers addressed this problem in comparison to other parameter study. Therefore, in this chapter, we discussed the impact of noise on Tunnel FET devices and circuits. The detail discussion has been done for the random telegraph noise, thermal noise, flicker noise, and shot noise for Si/Ge TFET and III-V TFETs. Recent research work for both low frequencies as well high frequency noise for different TFET device design has been discussed in details.",signatures:"Sweta Chander and Sanjeet Kumar Sinha",downloadPdfUrl:"/chapter/pdf-download/79186",previewPdfUrl:"/chapter/pdf-preview/79186",authors:[{id:"223387",title:"Dr.",name:"Sweta",surname:"Chander",slug:"sweta-chander",fullName:"Sweta Chander"},{id:"427030",title:"Dr.",name:"Sanjeet Kumar",surname:"Sinha",slug:"sanjeet-kumar-sinha",fullName:"Sanjeet Kumar Sinha"}],corrections:null},{id:"79872",title:"Plasmonic 2D Materials: Overview, Advancements, Future Prospects and Functional Applications",doi:"10.5772/intechopen.101580",slug:"plasmonic-2d-materials-overview-advancements-future-prospects-and-functional-applications",totalDownloads:162,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Plasmonics is a technologically advanced term in condensed matter physics that describes surface plasmon resonance where surface plasmons are collective electron oscillations confined at the dielectric-metal interface and these collective excitations exhibit profound plasmonic properties in conjunction with light interaction. Surface plasmons are based on nanomaterials and their structures; therefore, semiconductors, metals, and two-dimensional (2D) nanomaterials exhibit distinct plasmonic effects due to unique confinements. Recent technical breakthroughs in characterization and material manufacturing of two-dimensional ultra-thin materials have piqued the interest of the materials industry because of their extraordinary plasmonic enhanced characteristics. The 2D plasmonic materials have great potential for photonic and optoelectronic device applications owing to their ultra-thin and strong light-emission characteristics, such as; photovoltaics, transparent electrodes, and photodetectors. Also, the light-driven reactions of 2D plasmonic materials are environmentally benign and climate-friendly for future energy generations which makes them extremely appealing for energy applications. This chapter is aimed to cover recent advances in plasmonic 2D materials (graphene, graphene oxides, hexagonal boron nitride, pnictogens, MXenes, metal oxides, and non-metals) as well as their potential for applied applications, and is divided into several sections to elaborate recent theoretical and experimental developments along with potential in photonics and energy storage industries.",signatures:"Muhammad Aamir Iqbal, Maria Malik, Wajeehah Shahid, Waqas Ahmad, Kossi A. A. Min-Dianey and Phuong V. Pham",downloadPdfUrl:"/chapter/pdf-download/79872",previewPdfUrl:"/chapter/pdf-preview/79872",authors:[{id:"236073",title:"Dr.",name:"Phuong",surname:"Pham",slug:"phuong-pham",fullName:"Phuong Pham"},{id:"445754",title:"Dr.",name:"Muhammad Aamir",surname:"Iqbal",slug:"muhammad-aamir-iqbal",fullName:"Muhammad Aamir Iqbal"},{id:"445755",title:"Dr.",name:"Maria",surname:"Malik",slug:"maria-malik",fullName:"Maria Malik"},{id:"445756",title:"Dr.",name:"Wajeehah",surname:"Shahid",slug:"wajeehah-shahid",fullName:"Wajeehah Shahid"},{id:"445757",title:"Dr.",name:"Waqas",surname:"Ahmad",slug:"waqas-ahmad",fullName:"Waqas Ahmad"},{id:"464621",title:"Dr.",name:"Kossi A. A.",surname:"Min-Dianey",slug:"kossi-a.-a.-min-dianey",fullName:"Kossi A. A. Min-Dianey"}],corrections:null},{id:"80095",title:"Doping and Transfer of High Mobility Graphene Bilayers for Room Temperature Mid-Wave Infrared Photodetectors",doi:"10.5772/intechopen.101851",slug:"doping-and-transfer-of-high-mobility-graphene-bilayers-for-room-temperature-mid-wave-infrared-photod",totalDownloads:107,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"High-performance graphene-HgCdTe detector technology has been developed combining the best properties of both materials for mid-wave infrared (MWIR) detection and imaging. The graphene functions as a high mobility channel that whisks away carriers before they can recombine, further contributing to detection performance. Comprehensive modeling on the HgCdTe, graphene, and the HgCdTe-graphene interface has aided the design and development of this MWIR detector technology. Chemical doping of the bilayer graphene lattice has enabled p-type doping levels in graphene for high mobility implementation in high-performance MWIR HgCdTe detectors. Characterization techniques, including SIMS and XPS, confirm high boron doping concentrations. A spin-on doping (SOD) procedure is outlined that has provided a means of doping layers of graphene on native substrates, while subsequently allowing integration of the doped graphene layers with HgCdTe for final implementation in the MWIR photodetection devices. Successful integration of graphene into HgCdTe photodetectors can thus provide higher MWIR detector efficiency and performance compared to HgCdTe-only detectors. New earth observation measurement capabilities are further enabled by the room temperature operational capability of the graphene-enhanced HgCdTe detectors and arrays to benefit and advance space and terrestrial applications.",signatures:"Ashok K. Sood, John W. Zeller, Parminder Ghuman, Sachidananda Babu, Nibir K. Dhar, Randy N. Jacobs, Latika S. Chaudhary, Harry Efstathiadis, Samiran Ganguly, Avik W. Ghosh, Sheikh Ziauddin Ahmed and Farjana Ferdous Tonni",downloadPdfUrl:"/chapter/pdf-download/80095",previewPdfUrl:"/chapter/pdf-preview/80095",authors:[{id:"428664",title:"Prof.",name:"Nibir K.",surname:"Dhar",slug:"nibir-k.-dhar",fullName:"Nibir K. Dhar"},{id:"439626",title:"Dr.",name:"Samiran",surname:"Ganguly",slug:"samiran-ganguly",fullName:"Samiran Ganguly"},{id:"23657",title:"Dr.",name:"Ashok K.",surname:"Sood",slug:"ashok-k.-sood",fullName:"Ashok K. Sood"},{id:"210274",title:"Dr.",name:"John W.",surname:"Zeller",slug:"john-w.-zeller",fullName:"John W. Zeller"},{id:"444716",title:"Ms.",name:"Latika S.",surname:"Chaudhary",slug:"latika-s.-chaudhary",fullName:"Latika S. Chaudhary"},{id:"444719",title:"Dr.",name:"Randy N.",surname:"Jacobs",slug:"randy-n.-jacobs",fullName:"Randy N. Jacobs"},{id:"444720",title:"Dr.",name:"Parminder",surname:"Ghuman",slug:"parminder-ghuman",fullName:"Parminder Ghuman"},{id:"444721",title:"Dr.",name:"Sachidananda",surname:"Babu",slug:"sachidananda-babu",fullName:"Sachidananda Babu"},{id:"444724",title:"Prof.",name:"Harry",surname:"Efstathiadis",slug:"harry-efstathiadis",fullName:"Harry Efstathiadis"},{id:"444727",title:"Prof.",name:"Avik W.",surname:"Ghosh",slug:"avik-w.-ghosh",fullName:"Avik W. Ghosh"},{id:"451870",title:"Dr.",name:"Sheikh Ziauddin",surname:"Ahmed",slug:"sheikh-ziauddin-ahmed",fullName:"Sheikh Ziauddin Ahmed"},{id:"451871",title:"Dr.",name:"Farjana Ferdous",surname:"Tonni",slug:"farjana-ferdous-tonni",fullName:"Farjana Ferdous Tonni"}],corrections:null},{id:"79179",title:"Analysis of Heat Transfer in Non-Coaxial Rotation of Newtonian Carbon Nanofluid Flow with Magnetohydrodynamics and Porosity Effects",doi:"10.5772/intechopen.100623",slug:"analysis-of-heat-transfer-in-non-coaxial-rotation-of-newtonian-carbon-nanofluid-flow-with-magnetohyd",totalDownloads:130,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The study analyzed the heat transfer of water-based carbon nanotubes in non-coaxial rotation flow affected by magnetohydrodynamics and porosity. Two types of CNTs have been considered; single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs). Partial differential equations are used to model the problem subjected to the initial and moving boundary conditions. Employing dimensionless variables transformed the system of equations into ordinary differential equations form. The resulting dimensionless equations are analytically solved for the closed form of temperature and velocity distributions. The obtained solutions are expressed in terms of a complementary function error. The impacts of the embedded parameters are graphically plotted in different graphs and are discussed in detail. The Nusselt number and skin friction are also evaluated. The temperature and velocity profiles have been determined to meet the initial and boundary conditions. An augment in the CNTs’ volume fraction increases both temperature and velocity of the nanofluid as well as enhances the rate of heat transport. SWCNTs provides high values of Nusselt number compared to MWCNTs. For verification, a comparison between the present solutions and a past study is conducted and achieved excellent agreement.",signatures:"Wan Nura’in Nabilah Noranuar, Ahmad Qushairi Mohamad, Sharidan Shafie, Ilyas Khan, Mohd Rijal Ilias and Lim Yeou Jiann",downloadPdfUrl:"/chapter/pdf-download/79179",previewPdfUrl:"/chapter/pdf-preview/79179",authors:[{id:"190576",title:"Dr.",name:"Ilyas",surname:"Khan",slug:"ilyas-khan",fullName:"Ilyas Khan"},{id:"190595",title:"Dr.",name:"Sharidan",surname:"Shafie",slug:"sharidan-shafie",fullName:"Sharidan Shafie"},{id:"436205",title:"M.Sc.",name:"Wan Nura’in Nabilah",surname:"Noranuar",slug:"wan-nura'in-nabilah-noranuar",fullName:"Wan Nura’in Nabilah Noranuar"},{id:"436213",title:"Dr.",name:"Ahmad Qushairi",surname:"Mohamad",slug:"ahmad-qushairi-mohamad",fullName:"Ahmad Qushairi Mohamad"},{id:"436214",title:"Dr.",name:"Mohd Rijal",surname:"Ilias",slug:"mohd-rijal-ilias",fullName:"Mohd Rijal Ilias"},{id:"436215",title:"Dr.",name:"Lim Yeou",surname:"Jiann",slug:"lim-yeou-jiann",fullName:"Lim Yeou Jiann"}],corrections:null},{id:"79499",title:"Semiconductor Epitaxial Crystal Growth: Silicon Nanowires",doi:"10.5772/intechopen.100935",slug:"semiconductor-epitaxial-crystal-growth-silicon-nanowires",totalDownloads:80,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The topic of nanowires is one of the subjects of technological rapid-progress research. This chapter reviews the experimental work and the advancement of nanowires technology since the past decade, with more focus on the recent work. Nanowires can be grown from several materials including semiconductors, such as silicon. Silicon is a semiconductor material with a very technological importance, reflected by the huge number of publications. Nanowires made of silicon are of particular technological importance, in addition to their nanomorphology-related applications. A detailed description of the first successfully reported Vapor–Liquid–Solid (VLS) 1-D growth of silicon crystals is presented. The bottom-up approach, the supersaturation in a three-phase system, and the nucleation at the Chemical Vapor Deposition (CVD) processes are discussed with more focus on silicon. Positional assembly of nanowires using the current available techniques, including Nanoscale Chemical Templating (NCT), can be considered as the key part of this chapter for advanced applications. Several applied and conceptional methods of developing the available technologies using nanowires are included, such as Atomic Force Microscopy (AFM) and photovoltaic (PV) cells, and more are explained. The final section of this chapter is devoted to the future trend in nanowires research, where it is anticipated that the effort behind nanowires research will proceed further to be implemented in daily electronic tools satisfying the demand of low-weight and small-size electronic devices.",signatures:"Maha M. Khayyat",downloadPdfUrl:"/chapter/pdf-download/79499",previewPdfUrl:"/chapter/pdf-preview/79499",authors:[{id:"427861",title:"Associate Prof.",name:"Maha",surname:"Khayyat",slug:"maha-khayyat",fullName:"Maha Khayyat"}],corrections:null},{id:"79258",title:"Ultrathin Metal Hydroxide/Oxide Nanowires: Crystal Growth, Self-Assembly, and Fabrication for Optoelectronic Applications",doi:"10.5772/intechopen.101117",slug:"ultrathin-metal-hydroxide-oxide-nanowires-crystal-growth-self-assembly-and-fabrication-for-optoelect",totalDownloads:113,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The fundamental understanding of transition metal oxides nanowires’ crystal growth to control their anisotropy is critical for their applications in miniature devices. However, such studies are still in the premature stage. From an industrial point of view, the most exciting and challenging area of devices today is having the balance between the performance and the cost. Accordingly, it is essential to pay attention to the controlled cost-effective and greener synthesis of ultrathin TMOS NWs for industrial optoelectronic applications. This chapter provides a comprehensive summary of fundamental principles on the preperation methods to make dimensionality controlled anisotropic nanowires, their crystal growth studies, and optical and electrical properties. The chapter particularly addresses the governing theories of crystal growth processes and kinetics that controls the anisotropy and dimensions of nanowires. Focusing on the oriented attachment (OA) mechanism, the chapter describes the OA mechanism, nanocrystal’s self-assembly, interparticle interactions, and OA-directed crystal growth to improve the state-of-the art kinetic models. Finally, we provide the future perspective of ultrathin TMOS NWs by addressing their current challenges in optoelectronic applications. It is our understanding that the dimension, and single crystallinity of nanowires are the main contributors for building all functional properties, which arise from quasi-1-D confinement of nanowire growth.",signatures:"Gayani Pathiraja and Hemali Rathnayake",downloadPdfUrl:"/chapter/pdf-download/79258",previewPdfUrl:"/chapter/pdf-preview/79258",authors:[{id:"323782",title:"Prof.",name:"Hemali",surname:"Rathnayake",slug:"hemali-rathnayake",fullName:"Hemali Rathnayake"},{id:"427650",title:"Dr.",name:"Gayani",surname:"Pathiraja",slug:"gayani-pathiraja",fullName:"Gayani Pathiraja"}],corrections:null},{id:"79858",title:"One-Dimensional Metal Oxide Nanostructures for Chemical Sensors",doi:"10.5772/intechopen.101749",slug:"one-dimensional-metal-oxide-nanostructures-for-chemical-sensors",totalDownloads:128,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The fabrication of chemical sensors based on one-dimensional (1D) metal oxide semiconductor (MOS) nanostructures with tailored geometries has rapidly advanced in the last two decades. Chemical sensitive 1D MOS nanostructures are usually configured as resistors whose conduction is altered by a charge-transfer process or as field-effect transistors (FET) whose properties are controlled by applying appropriate potentials to the gate. This chapter reviews the state-of-the-art research on chemical sensors based on 1D MOS nanostructures of the resistive and FET types. The chapter begins with a survey of the MOS and their 1D nanostructures with the greatest potential for use in the next generation of chemical sensors, which will be of very small size, low-power consumption, low-cost, and superior sensing performance compared to present chemical sensors on the market. There follows a description of the 1D MOS nanostructures, including composite and hybrid structures, and their synthesis techniques. And subsequently a presentation of the architectures of the current resistive and FET sensors, and the methods to integrate the 1D MOS nanostructures into them on a large scale and in a cost-effective manner. The chapter concludes with an outlook of the challenges facing the chemical sensors based on 1D MOS nanostructures if their massive use in sensor networks becomes a reality.",signatures:"Esther Hontañón and Stella Vallejos",downloadPdfUrl:"/chapter/pdf-download/79858",previewPdfUrl:"/chapter/pdf-preview/79858",authors:[{id:"425601",title:"Dr.",name:"Esther",surname:"Hontañón",slug:"esther-hontanon",fullName:"Esther Hontañón"},{id:"444852",title:"Dr.",name:"Stella",surname:"Vallejos",slug:"stella-vallejos",fullName:"Stella Vallejos"}],corrections:null},{id:"80152",title:"Energy Storage Properties of Topochemically Synthesized Blue TiO2 Nanostructures in Aqueous and Organic Electrolyte",doi:"10.5772/intechopen.102186",slug:"energy-storage-properties-of-topochemically-synthesized-blue-tio-sub-2-sub-nanostructures-in-aqueous",totalDownloads:87,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This book chapter discusses the topochemical synthesis of blue titanium oxide (b-TiO2) and their application as electrode material for supercapacitor devices in aqueous and organic electrolytes. The formation mechanism of b-TiO2 via topochemical synthesis and their characterization using X-ray diffraction, UV–visible, photoluminescence, electron spin resonance spectroscopy, laser Raman spectrum, X-ray photoelectron spectroscopy, and morphological studies (FESEM and HR-TEM) are discussed in detail. The supercapacitive properties of b-TiO2 electrode were studied using both aqueous (Na2SO4) and organic (TEABF4) electrolytes. The b-TiO2 based symmetric-type supercapacitor (SC) device using TEABF4 works over a wide voltage window (3 V) and delivered a high specific capacitance (3.58 mF cm−2), possess high energy density (3.22 μWh cm−2) and power density (8.06 mW cm−2) with excellent cyclic stability over 10,000 cycles. Collectively, this chapter highlighted the use of b-TiO2 sheets as an advanced electrode for 3.0 V supercapacitors.",signatures:"Parthiban Pazhamalai, Karthikeyan Krishnamoorthy and Sang-Jae Kim",downloadPdfUrl:"/chapter/pdf-download/80152",previewPdfUrl:"/chapter/pdf-preview/80152",authors:[{id:"81419",title:"Prof.",name:"Sang-Jae",surname:"Kim",slug:"sang-jae-kim",fullName:"Sang-Jae Kim"},{id:"278690",title:null,name:"Karthikeyan",surname:"Krishnamoorthy",slug:"karthikeyan-krishnamoorthy",fullName:"Karthikeyan Krishnamoorthy"},{id:"278691",title:"Dr.",name:"Parthiban",surname:"Pazhamalai",slug:"parthiban-pazhamalai",fullName:"Parthiban Pazhamalai"}],corrections:null},{id:"79227",title:"Silk Fibroin Nanoparticles: Synthesis and Applications as Drug Nanocarriers",doi:"10.5772/intechopen.100386",slug:"silk-fibroin-nanoparticles-synthesis-and-applications-as-drug-nanocarriers",totalDownloads:164,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The use of nanoparticles in biomedical fields is a very promising scientific area and has aroused the interest of researchers in the search for new biodegradable, biocompatible and non-toxic materials. This chapter is based on the features of the biopolymer silk fibroin and its applications in nanomedicine. Silk fibroin, obtained from the Bombyx mori silkworm, is a natural polymeric biomaterial whose main features are its amphiphilic chemistry, biocompatibility, biodegradability, excellent mechanical properties in various material formats, and processing flexibility. All of these properties make silk fibroin a useful candidate to act as nanocarrier. In this chapter, the structure of silk fibroin, its biocompatibility and degradability are reviewed. In addition, an intensive review on the silk fibroin nanoparticle synthesis methods is also presented. Finally, the application of the silk fibroin nanoparticles for drug delivery acting as nanocarriers is detailed.",signatures:"Guzmán Carissimi, Mercedes G. Montalbán, Marta G. Fuster and Gloria Víllora",downloadPdfUrl:"/chapter/pdf-download/79227",previewPdfUrl:"/chapter/pdf-preview/79227",authors:[{id:"187906",title:"Prof.",name:"Gloria",surname:"Víllora",slug:"gloria-villora",fullName:"Gloria Víllora"},{id:"194675",title:"Mrs.",name:"Mercedes G.",surname:"Montalbán",slug:"mercedes-g.-montalban",fullName:"Mercedes G. Montalbán"},{id:"245952",title:"MSc.",name:"Guzmán",surname:"Carissimi",slug:"guzman-carissimi",fullName:"Guzmán Carissimi"},{id:"429265",title:"MSc.",name:"Marta G.",surname:"Fuster",slug:"marta-g.-fuster",fullName:"Marta G. Fuster"}],corrections:null},{id:"78717",title:"Nanoparticles as Drug Delivery Systems",doi:"10.5772/intechopen.100253",slug:"nanoparticles-as-drug-delivery-systems",totalDownloads:558,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter presents a review on the design of nanoparticles which have been proposed as drug delivery systems in biomedicine. It will begin with a brief historical review of nanotechnology including the most common types of nanoparticles (metal nanoparticles, liposomes, nanocrystals and polymeric nanoparticles) and their advantages as drug delivery systems. These advantages include the mechanism of increased penetration and retention, the transport of insoluble drugs and the controlled release. Next, the nanoparticle design principles and the routes of administration of nanoparticles (parental, oral, pulmonary and transdermal) are discussed. Different routes of elimination of nanoparticles (renal and hepatic) are also analyzed.",signatures:"Guzmán Carissimi, Mercedes G. Montalbán, Marta G. Fuster and Gloria Víllora",downloadPdfUrl:"/chapter/pdf-download/78717",previewPdfUrl:"/chapter/pdf-preview/78717",authors:[{id:"187906",title:"Prof.",name:"Gloria",surname:"Víllora",slug:"gloria-villora",fullName:"Gloria Víllora"},{id:"194675",title:"Mrs.",name:"Mercedes G.",surname:"Montalbán",slug:"mercedes-g.-montalban",fullName:"Mercedes G. Montalbán"},{id:"245952",title:"MSc.",name:"Guzmán",surname:"Carissimi",slug:"guzman-carissimi",fullName:"Guzmán Carissimi"},{id:"429265",title:"MSc.",name:"Marta G.",surname:"Fuster",slug:"marta-g.-fuster",fullName:"Marta G. Fuster"}],corrections:null},{id:"79442",title:"Biological Synthesis of Metallic Nanoparticles from Different Plant Species",doi:"10.5772/intechopen.101355",slug:"biological-synthesis-of-metallic-nanoparticles-from-different-plant-species",totalDownloads:129,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Green chemistry for the synthesis of different nanoparticles (NPs) from metal has become a new and promising field of research in nanotechnology in recent years. The inspire applications of metal oxide NPs have attracted the interest of researchers around the world. Various physical, chemical and biological methods in material science are being adapted to synthesize different types of NPs. Green synthesis has gained widespread attention as a sustainable, reliable, and eco-friendly protocol for biologically synthesizing a wide range of metallic NPs. Green synthesis has been proposed to reduce the use of hazardous compounds and as a state of a harsh reaction in the production of metallic NPs. Plants extract used for biosynthesis of NPs such as silver (Ag), cerium dioxide (C2O2), copper oxide (CuO), Gold (Au), titanium dioxide (TiO2), and zinc oxide (ZnO). This review article gives an overview of the plant-mediated biosynthesis of NPs that are eco-friendly and have less hazardous chemical effects.",signatures:"Kalyan Singh Kushwah and Deepak Kumar Verma",downloadPdfUrl:"/chapter/pdf-download/79442",previewPdfUrl:"/chapter/pdf-preview/79442",authors:[{id:"334136",title:"Ph.D. Student",name:"Kalyan Singh",surname:"Kushwah",slug:"kalyan-singh-kushwah",fullName:"Kalyan Singh Kushwah"},{id:"426969",title:"Mr.",name:"Deepak Kumar",surname:"Verma",slug:"deepak-kumar-verma",fullName:"Deepak Kumar Verma"}],corrections:null},{id:"80585",title:"Nanofibers: Production, Characterization, and Tissue Engineering Applications",doi:"10.5772/intechopen.102787",slug:"nanofibers-production-characterization-and-tissue-engineering-applications",totalDownloads:66,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Among all nanostructured materials, nanofibers (NFs) are the one class that is widely used in tissue engineering (TE) and regenerative medicine (RM) areas. NFs can be produced by a variety of different methods, so they can be used almost for any tissue engineering process with appropriate modifications. Also, the variety of materials that can form nanofibers, production methods, and application fields increase the value of NFs greatly. They are almost suitable for any tissue engineering applications due to their tunable properties. Hopefully, this chapter will provide brief information about the production methods (electrospinning, wet spinning, drawing, etc.), characterization methods (Scanning Electron Microscopy, Transmission Electron Microscopy, Atomic Force Microscopy, etc.), and tissue engineering applications (core-shell fibers, antibacterial fibers, nanoparticle-incorporated fibers, drug-loaded fibers, etc.) of NFs.",signatures:"Ece Bayrak",downloadPdfUrl:"/chapter/pdf-download/80585",previewPdfUrl:"/chapter/pdf-preview/80585",authors:[{id:"427785",title:"Ph.D.",name:"Ece",surname:"Bayrak",slug:"ece-bayrak",fullName:"Ece Bayrak"}],corrections:null},{id:"79338",title:"Composite Metamaterials: Classification, Design, Laws and Future Applications",doi:"10.5772/intechopen.100861",slug:"composite-metamaterials-classification-design-laws-and-future-applications",totalDownloads:117,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The development of science and applications have reached a stage where the naturally existed materials are not meeting the required properties. Metamaterials (MMs) are artificial materials that obtain their properties from their accurately engineered meta-atoms rather than the characteristics of their constituents. The size of the meta-atom is small compared to light’s wavelength. A metamaterial (MM) is a term means beyond material which has been engineered in order to possess properties that does not exist in naturally-found materials. Currently, they are made of multiple elements such as plastics and metals. They are being organized in iterating patterns at a scale that is smaller than wavelengths of the phenomena it influences. The properties of the MMs are not derived from the forming materials but their delicate size, geometry, shape, orientation, and arrangement. These properties maintain MMs to manipulate the electromagnetic waves via promoting, hindering, absorbing waves to attain an interest that goes beyond the natural materials’ potency. The apt design of MMs maintains them of influencing the electromagnetic radiation or sound in a distinctive technique never found in natural materials. The potential applications of MMs are wide, starting from medical, aerospace, sensors, solar-power management, crowd control, antennas, army equipment and reaching earthquakes shielding and seismic materials.",signatures:"Tarek Fawzi and Ammar A.M. Al-Talib",downloadPdfUrl:"/chapter/pdf-download/79338",previewPdfUrl:"/chapter/pdf-preview/79338",authors:[{id:"425395",title:"Ph.D. Student",name:"Tarek",surname:"Fawzi",slug:"tarek-fawzi",fullName:"Tarek Fawzi"},{id:"437661",title:"Dr.",name:"Ammar",surname:"A.M. Al-Talib",slug:"ammar-a.m.-al-talib",fullName:"Ammar A.M. Al-Talib"}],corrections:null},{id:"79747",title:"Nanocomposite Material Synthesized Via Horizontal Vapor Phase Growth Technique: Evaluation and Application Perspective",doi:"10.5772/intechopen.101637",slug:"nanocomposite-material-synthesized-via-horizontal-vapor-phase-growth-technique-evaluation-and-applic",totalDownloads:108,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The synthesis of nanomaterials has been reported by many researchers using different methods. One of the methods that can be used with perfect pureness and have less pollution in the synthesized materials results is the vapor phase growth technique (VPGT). Several types of nano shapes materials were reported such as nanoparticles, nanorods, nano triangular, nanosphere, and nanocrystal. The synthesis method has a fundamental process where the nanomaterials evaporated and condensed based on the temperature difference. There are three important variables, i.e., stochiometric ratio of source materials, temperature and baking time. The synthesis was occured in the quartz tube and sealed in the vacuum condition. This create the material was synthesis in pure and isolated conditions. The application of the nanomaterials synthesized via Horizontal Vapor Phase Growth (HVPG) can be implemented in anti-pathogen, anti-bacterial, gas sensing and coating applications.",signatures:"Muhammad Akhsin Muflikhun, Rahmad Kuncoro Adi and Gil Nonato C. Santos",downloadPdfUrl:"/chapter/pdf-download/79747",previewPdfUrl:"/chapter/pdf-preview/79747",authors:[{id:"422388",title:"Assistant Prof.",name:"Muhammad",surname:"Akhsin Muflikhun",slug:"muhammad-akhsin-muflikhun",fullName:"Muhammad Akhsin Muflikhun"},{id:"446220",title:"Dr.",name:"Rahmad",surname:"Kuncoro Adi",slug:"rahmad-kuncoro-adi",fullName:"Rahmad Kuncoro Adi"},{id:"446221",title:"Dr.",name:"Gil",surname:"Nonato C. Santos",slug:"gil-nonato-c.-santos",fullName:"Gil Nonato C. Santos"}],corrections:null},{id:"80747",title:"Recent Advances in Nano-Enabled Fertilizers towards Sustainable Agriculture and Environment: A Mini Review",doi:"10.5772/intechopen.103053",slug:"recent-advances-in-nano-enabled-fertilizers-towards-sustainable-agriculture-and-environment-a-mini-r",totalDownloads:44,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Food creation be directed expand uniquely to take care of the developing human populace; however, this should be accomplished while at the same time decreasing unfriendly natural effects. In such manner, there is expanding interest in the utilization of nanomaterials as composts for further developing plant mineral sustenances that are crippling Indian agriculture. To address these problems, there is a need to explore one of the frontier technologies like nano-technology to precisely detect and deliver correct quantity of nutrients that promote the productivity. Nano-technology uses synthesized materials that are 10–9 nm in size to improve the productivity, yield and crop quality. Research has proved beyond doubt that the nano-fertilizers that contain readily available nutrients in nano-scale have increased uptake, absorption and improved bioavailability in the plant body compared to the conventional bulk equivalents. This audit assesses the current writing on ENMs utilized as pesticides and manures, and features basic information holes that should be addressed to guarantee maintainable use of nanotechnology in horticulture to accomplish worldwide food security. Designing nanoparticles-based nanofertilizers offer advantages in crop nourishment of the board by upgrading abiotic stress resilience and improving farming efficiency towards the advancement of brilliant and supportable future horticulture.",signatures:"Challa Gangu Naidu, Yarraguntla Srinivasa Rao, Dadi Vasudha and Kollabathula Vara Prasada Rao",downloadPdfUrl:"/chapter/pdf-download/80747",previewPdfUrl:"/chapter/pdf-preview/80747",authors:[{id:"426790",title:"Assistant Prof.",name:"Dr Gangu Naidu",surname:"Challa",slug:"dr-gangu-naidu-challa",fullName:"Dr Gangu Naidu Challa"},{id:"452727",title:"Prof.",name:"Srinivasa Rao",surname:"Y",slug:"srinivasa-rao-y",fullName:"Srinivasa Rao Y"},{id:"452728",title:"Dr.",name:"Vasudha",surname:"D",slug:"vasudha-d",fullName:"Vasudha D"},{id:"452729",title:"Prof.",name:"Vara Prasada Rao",surname:"K",slug:"vara-prasada-rao-k",fullName:"Vara Prasada Rao K"}],corrections:null},{id:"79697",title:"Electrochemical Impedance Spectroscopy and Its Applications",doi:"10.5772/intechopen.101636",slug:"electrochemical-impedance-spectroscopy-and-its-applications",totalDownloads:130,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Electrochemistry has become an important and recognized field for the future since many of its approaches contemplate the establishment of stable energy supplies and the minimization of our impact on the environment. In this regard, electrochemistry can face both objectives by studying the electrode/solution interface. As a result, different electrochemical techniques can be used to study the interface to understand the electron transfer phenomena in different reactions. Considering this, one of the most useful techniques to understand the electrode/solution interface is electrochemical impedance spectroscopy. This technique allows us to describe the electrode behavior in the presence of a certain electrolyte in terms of electrical parameters such as resistances and capacitances, among others. With this information, we can infer the electrochemical behavior toward a specific reaction and the capacity of the electrode to carry on the electron transfer depending on its resistance (impedance) values. The aim of this chapter is to go from the theory, based on Ohm’s Law and its derivations, to actual applications. This will lead us to characterize the solution, electrode, and the interface between these two phases based on their electrical components by using an equivalent electrical circuit, such as the Randles equivalent circuit.",signatures:"Camila Pía Canales",downloadPdfUrl:"/chapter/pdf-download/79697",previewPdfUrl:"/chapter/pdf-preview/79697",authors:[{id:"428140",title:"Dr.",name:"Camila",surname:"Pía Canales",slug:"camila-pia-canales",fullName:"Camila Pía Canales"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"10061",title:"21st Century Surface Science",subtitle:"a Handbook",isOpenForSubmission:!1,hash:"69253b3c7ba801a5fcd9c47827345f93",slug:"21st-century-surface-science-a-handbook",bookSignature:"Phuong Pham, Pratibha Goel, Samir Kumar and Kavita Yadav",coverURL:"https://cdn.intechopen.com/books/images_new/10061.jpg",editedByType:"Edited by",editors:[{id:"236073",title:"Dr.",name:"Phuong",surname:"Pham",slug:"phuong-pham",fullName:"Phuong Pham"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6408",title:"Novel Nanomaterials",subtitle:"Synthesis and Applications",isOpenForSubmission:!1,hash:"f3585d338d78e4d31c200d9991b03692",slug:"novel-nanomaterials-synthesis-and-applications",bookSignature:"George Z. 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A Multidimensional Approach",slug:"child-abuse-and-neglect-a-multidimensional-approach",publishedDate:"July 11th 2012",bookSignature:"Alexander Muela",coverURL:"https://cdn.intechopen.com/books/images_new/2663.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"138437",title:"Dr.",name:"Alexander",middleName:null,surname:"Muela Aparicio",slug:"alexander-muela-aparicio",fullName:"Alexander Muela Aparicio"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11504",leadTitle:null,title:"Kalman Filter - Engineering Applications\ufeff",subtitle:null,reviewType:"peer-reviewed",abstract:"\r\n\tThe book will aim to examine the Kalman Filter (KF), also known as the Kalman Bucy Filter (KBF), from the standpoint of its engineering implementation. The intended purpose of the book will be to extend the circle of users of the Kalman filter by considering it not as a means of theoretical analysis, but rather as a powerful tool for the design of a technical system. The editor accumulated experience of using suboptimal KF in various aerospace applications and would wish to share it with the pool of potential users and like-minded specialists. Instead of the formal programming of the recursive KF equations some simple and robust sub-optimal forms are proposed. For example, developed by the editor, suboptimal (KBF), with bounded grows of memory (FBGM) and its steady-state form- the time-invariant filter with constant coefficients is aimed to be considered. This allows the developer to use the KBF not only for system state estimation but for control as well. Proceeding in this way developer can be guaranteed the filter stability and robustness in many practically uncertain situations when the statistic characteristics of system disturbances and measured errors are not entirely known. A guaranteed approach with using an equivalent white noise is also aimed to be considered. Some representative examples from typical aerospace systems (the editor’s main professional field) are intended to be presented. Summarizing the above, it can be emphasized that when implementing the KF it is always useful to replace the art of programming with the experience of designing conventional robust systems having an idealistic estimate of maximum (best) of achievable performance. This would prevent the system's real-time computer from many possible situations with “empty “computations and even to the divergence of the computational process. It can also show that the filter is not a magic mill and cannot achieve the desired performance if it cannot be achieved in principle, better that it can be “promised” by the KF quadratic criterion minimum, or if some state vector components are not observable and controllable.
",isbn:"978-1-80356-576-7",printIsbn:"978-1-80356-575-0",pdfIsbn:"978-1-80356-577-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"4c3e68adcaeaa44f9fbfe9bb19bdd55b",bookSignature:"Dr. Yuri Kim",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11504.jpg",keywords:"Separation Theorem, Extended Kalman Filter, Covariance Matrix, Riccati Equation, FBGM, Analytical Implementation Forms, Physical Implementation Forms, Steady State Filter, Inertial Navigation System, Global Positioning System, Controllability, Multisensory Navigation",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 15th 2022",dateEndSecondStepPublish:"June 2nd 2022",dateEndThirdStepPublish:"August 1st 2022",dateEndFourthStepPublish:"October 20th 2022",dateEndFifthStepPublish:"December 19th 2022",remainingDaysToSecondStep:"11 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Prof. Y.V. Kim is a Doctor of Technical Science, having a broad and wealthy international scientific, engineering, and teaching experience, obtained in the former USSR, Israel, and Canada. He has many scientific publications and implemented inventions dedicated to Aerospace GN&C.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"316140",title:"Dr.",name:"Yuri",middleName:null,surname:"Kim",slug:"yuri-kim",fullName:"Yuri Kim",profilePictureURL:"https://mts.intechopen.com/storage/users/316140/images/system/316140.jpg",biography:"Yuri Kim\n24 Buttenut, Gatineau, QC, Canada\nTel : 1-(514)- 466-1033, e-mail: yurikim@hotmail.ca\n\nHIGHLIGHTS OF QUALIFICATIONS:\n\nExperienced scientist, engineer and manager with internationally recognized achievements in area of Aerospace Avionics, (GN&C); Analysis, design (HW&SW), integration, testing and operation for various aerospace platforms and missions. \n\nGained a broad experience in preparation of technical documents for Joint (Industry-Customer) State Commissions for the acceptance (commissioning) of Aerospace Avionics, Navigation and Special application experimental equipment for further serial production, and operational support. Last works have been dedicated to R&D projects developing new Satellite Navigation Control Technology and customer support of Canadian satellites Control system design.\n\n\nACADEMIC DEGREES:\n\n 1991 *Doctor of Technical Science Diploma in Aerospace Vehicles Guidance \n Navigation and Control \n Scientific Council of State Institute of Automatic Systems, Ministry of Aviation\n Industry of USSR, Moscow\n (Recognized by Canadian Professional Counsel of Engineers) \n1982 * Senior Scientific Fellow Diploma in Gyroscopes and Navigation systems \n Capital Certification Commission of Scientists, Ministry of High Education of\n USSR, Moscow.\n (Recognized by Canadian Professional Counsel of Engineers)\n1974 * Candidate of Technical Science Diploma in Aerospace Navigation\n and Control Systems (Accredited as Ph.D by York University, Toronto.)\n Scientific Council of Moscow Aviation Institute, Moscow.\n1970 * Engineer Electromechanic Diploma in Gyro and Navigation systems,\n Faculty of Flight Apparatuses Control Systems, Moscow Aviation Institute, \n Moscow (Accredited as between Masters Degree and Bachelor Degree by\n York University, Toronto).\n1965 * Radio and TV Systems Technician Certificate, Dnepropetrovsk Technical School \n of preparation of technical specialists for Soviet Army, Military Aviation and \n Navy.\n\nMILITARY EDUCATION:\n\n1970 * Engineer in ballistic rocket control system, Military Faculty of MAI, last rank senior engineer-lieutenant (in reserve)\n\n\n\nEMPLOYMENT HISTORY:\nA. GOVERNMENT\n\nAt present - Canadian Space Agency, Space Science and Technology Division, David Florida Laboratory\n\n Senior Aerospace System engineer \n\n° Performing, developing and supporting phases of design, testing, commissioning and \n operation for space vehicle orbit and attitude control systems, in particular: Tecsas, Scope, \n J2Sat, Small satellite, M3Msat, Cassiopea, Neossat, RCM, PCW\n\n° Reviewing and commenting on Attitude Control systems design documentations, related to \n all phases of system development commissioning and operation\n \n° Supporting Aerospace Industry R&D projects funding by CSA (STDP) as Scientific\n Authority, in particular: Microwheel (Dynacon), LOCOOS (NGC), PCW (Bristol)\n\n° Providing expertise on new initiatives for Space Exploration and Utilization regarding \n Attitude and Orbital Control and possible development of Canadian space launcher\n\n° Developing basic mathematical (Simulink/Matlab) simulator for developing the \n requirements and expected performance of AODCS for new space vehicles\n\n° Developing new basic technology (based on Kalman Filter) for satellite attitude\n determination and sensor calibration, developing of FF test-bed equipment and GPS \n navigation in environment of CSA laboratory, developing of methods of ACS sensors\n calibration, measuring and compensation of satellite residual magnetic moment, experimental determination of satellite inertia matrix during ACS integration tests\n\n° Interacting with Space Industry and Universities in the problems, related to development of \n new methods and systems for space vehicle attitude and orbit determination and control\n \n° Sharing with International Aerospace community CSA achievements and experience in\n development of new technologies and methods for space vehicle attitude and orbit \n determination and control through publications, presentations and participation in scientific\n conferences, meetings and symposiums as well as maintaining an awareness about new \n technological advancements\n \n° Providing professional training for students and post. Graduates in the area of Orbital and\n Attitude Dynamic and Control\n\nB. INDUSTRIAL\n\nSept. 1998 – Feb. 1999 – Olympia Engineering Ltd. (Toronto)\n\nResearch and Development Engineer\n\n•\tDevelopment of measuring instrument for measuring remote measuring of micro- deformations of machinery (milling machine) equipment\n•\tResearch and testing of differential GPS survey equipment and antennas in environment of industrial facility for developing a new remote method for the measuring of machinery micro-deformations\n\n\n\n\nFeb.1999 – Jun.2002 – Saskatoon Engineering Division of Calian Company, \n Radarsat-1 Operation Team (CSA, Montreal)\n\nAttitude Control System Analyst\n\n•\tWorking as RADARSAT-1 Attitude Control System Analyst performing day-to-day operation TLM data analysis; reporting, monitoring and solving ACS flight anomaly problems, maintaining ACS software and performance \n•\tAuthor of many reports (see attached list of publications), devoted to solving of Radarsat-1 non-benign Safe Hold Mode problem, Momentum Wheel failure problems and improvement of the performance of attitude determination method with Magnetometer and Sun Sensor (back up, ADM3 mode for the case of potential failure of Horizon Scanner).\n•\tPreparation and implementation of the solution for RADARSAT-1 operation without failed Momentum Wheels, that saved the satellite mission after the wheel failures\n(This work was prolonged after in CSA and awarded by the Canadian Government Award for the invention used by the Government)\n•\tDesign and implementation of new dynamic simulators (based on Simulink\ntoolbox) for Radarsat-1 ACS for operation support\n•\tPreparation for operation of new Canadian satellites Scisat and RADARSAT-2 \n\n\n\nJan. 1994 – Sep. 1997 – Israel Aviation Industry (IAI factories: TASHAN, LAHAV)\n\nAvionics system engineer\n\n•\tResearch and preliminary design of the Special Data Fusion System for a fighter-interceptor\n•\tIntegration of Inertial Navigation System with Global Position System into Upgraded Avionics Suit and installation in aircraft cockpit for A/C – trainer T-38\n\nNov. 1977 – Apr. 1993 – Moscow Research and Design Institute of Electromechanic and Automatic (formerly P/B: M5537, presently “Aviapribor” Corporation)\n\n \nHead of Division (R&D in Pilot-Navigation Systems)\n\n•\tLeadership of the Division, performing planning, financial and methodological duties, related to this position, reporting to the R&D deputy director of the Institute\n•\tResponsibility for Pilot-Navigation System integration, interaction, tests and transferring for serial production and operational support\n•\tInitiation and methodical leadership of innovative research and development projects\n•\tReviewing, commenting and implementation of Technical standards and Navigation norms\nas well as sharing progressive methods and results within Aerospace organizations within former USSR\n \n Head of Department (INS and Flight Management System SW Development)\n\n•\tLeadership and performing of duties of Head of Department \n•\tResponsibility for the prospective research and preliminary design of the Inertial Navigation Systems (INS) and Flight Management Systems (FMS)\n•\tDesign of the INS and FMS algorithms and simulation of expected performance\n•\tDevelopment of INS/FMS flight code\n•\tDevelopment of test procedures and simulators for FMS, and pilot nav.complexis for aircrafts \n•\tResponsibility for system performance analysis in the ground and flight tests\n\n Head of Sector (System Flight Test data analysis) \n\n•\tLeadership of the Sector\n•\tDevelopment of ground and flight test simulation procedures and requirements for test equipment and simulators, for flight test aircraft measuring equipment, installation and recorded data processing\n•\tDesign of Estimation and Identification algorithms for ground and flight data processing\n•\tTest data analysis, preparation of test results analysis reports and conclusions\n\n Senior Scientific Fellow\n\n•\tResearch, development and principal design of the special Suboptimal Kalman Filter for the fusion of data of various navigation sensors for aviation and space platforms\n•\tDevelopment of new Guidance and Navigation methods for aviation and space platforms\n•\tAnalysis of INS and FMS performance in ground and flight tests\n\nC. ACADEMIC \n\n1977–1993 – Moscow Aviation Institute, Moscow Institute of Instrument -\n Making, Aviation Industry Ministry Upgrade Qualification Institute\n(Part Time) Professor, Associate professor, Chairmen of State Diploma Commission,\n Member of Scientific Council\n•\tLecturer of the disciplines: Applied Oscillation, Theory (MIIM), Design of Instruments (MIIM), Integrated Navigation Systems (MUQI)\n•\tChairman of the State Diploma Commission -Gyro Instruments and Systems (MAI)\n•\tLeadership of postgraduates, participation in sessions of Scientific Council (MAI)\n•\tMethodical management of cathedra of Orientation and Navigation in MAI \n\n2009 McGill University, Montreal\n\nPart time lecturer for course (in English): Aircraft Performance, Stability and Control\n\n1970–1977 – Moscow Aviation Institute \n(Full Time) Associate Professor, Senior Researcher, Assistant Lecturer \n•\tLecturer of the courses: Spacecraft orbital mechanics and attitude determination and control, Inertial Navigation Systems, Gyro Instruments and Systems\n•\tResearch and development of suboptimal robust estimation methods for navigation data processing\n•\tResponsibility for the navigation systems laboratory\n•\tDeputy head of cathedra of Orientation and Navigation\n\nFIELDS OF THEORETICAL AND METHODOLOGIC EXPERTISE:\n \n•\tSpace vehicle Orbit and Attitude determination and control\n•\tGyro instruments and systems\n•\tRadio navigation systems\n•\tInertial Navigation systems\n•\tAirplane Navigation and Control\n•\tAnalytical mechanics \n•\tApplied oscillation theory\n•\tAutomatic control theory\n•\tStochastic estimation theory\n\nENGINEERING EXPERIENCE:\n\n•\tFlight and laboratory tests of Aerospace Avionics Equipment\n•\tDistribution of mission requirements between Aerospace vehicle subsystems, definition of functions and ICD \n•\tSpacecraft operation and performance maintenance\n•\tAvionics system (hardware and software) development and testing (autonomously and integration)\n•\tInertial navigation systems\n•\t Development of Avionics for Soviet Military aircrafts: Tu-142, Tu-95MC, An-124, An-70, A-40, Soviet Space shuttle “Buran” (responsibility for preliminary design of radio-navigation automatic landing system), \n•\tIsrael (IAI) upgrade of Avionics system for T-38 (USA Air force trainer) \n•\tOperation and modification in space Canadian Satellite RADARSAT-1 Attitude Control system\n•\tParticipation in commissioning of ACS of Canadian Satellite Scisat\n•\tDevelopment of a generic mathematical simulator for satellite AODCS analysis and simulation of expected performance for a family of Canadian new generation small satellites\n\nSCIENTIFIC EXPERIENCE:\n\n•\tTheoretical and experimental investigation in the fields of S/C Orbital and Attitude Control\n•\tKalman Filter suboptimization and robust guarantee estimation theory development: authorship of new Suboptimal Kalman Filter modification, methods of INS correction and calibration, Geomagnetic Inertial Navigation System\n•\tResearch in areas of ACS and INS sensors development, their performance improvement\n•\tVarious Avionics Systems Mathematical models development and mathematical and semi-natural simulation\n•\tCoordination of research and development projects related to Aerospace equipment performed by Universities and Industries\n•\tScientific reports and articles reviewing and editorship \n•\tMembership in Scientific Counsels and Commissions\n•\tTutorship of under-graduate, graduated and post -graduate students \n\n•\tScientific reports and inventions in the field of GN&C for aircraft and spacecraft methods development \n•\tSeveral articles dedicated to the development of new methods in estimation theory: new suboptimal Kalman Filter with limited growth of the memory, observability and factor of state vector components estimation, guaranteed ellipsoidal estimation and stochastic estimation comparison \n\nLANGUAGES:\n \n•\tEnglish, Russian, Ukrainian, Hebrew, French (beginning level)\n•\tProgramming languages: Matlab/Simulinc/С",institutionString:"Canadian Space Agency",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Canadian Space Agency",institutionURL:null,country:{name:"Canada"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"453623",firstName:"Silvia",lastName:"Sabo",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/453623/images/20396_n.jpg",email:"silvia@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and 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An increasing numbers of patients with CxHD are encountered in our everyday practice. It is therefore timely and appropriate to start addressing the somewhat-neglected issue of myocardial ischemia in this patient population [2].
CxHD is, by definition, cardiovascular disease present at birth. It refers to anatomic defects and gross cardiac abnormalities due to an embryologic malformation in the structural development of the heart and major blood vessels, which is actually of functional significance [3]. Most CxHD occur due to gross structural developmental cardiovascular anomalies such as septal defects, stenosis or atresia of valves, hypoplasia or absence of one ventricle, or abnormal connections between great vessels and the heart. A few children are also born with arrhythmias (mainly conduction defects), and hypertrophic or dilated cardiomyopathy, although these are usually present later in childhood or adulthood. CxHD are the most common of all congenital malformations, with a reported incidence of 6 to 8 cases per 1,000 live births, and in an even higher percentage of foetuses [4]. In some studies this incidence reaches 12 to 14 per 1,000 live births [5].
There is a great number of recognized heart defects occurring alone and in combination, ranging in severity from hemodynamically insignificant to extremely complex and life threatening conditions (Table 1). Although there may be genetic or environmental situations that can affect the development of heart defects, in the majority of cases the cause is considered multifactorial, with no specific identifiable trigger. Only approximately 15% of cases of CxHD can be traced to a known cause [6]. Some types of CxHD can be related to chromosome or gene defects, environmental factors or a multifactorial aetiology [7]. Only 2% of all cases of CxHD can be attributed to known environmental factors. Risk factors, such as maternal insulin-dependent diabetes mellitus and phenylketonuria, are well known as two of the leading causes of CxHD. Other reported risk factors include maternal obesity, alcohol use in pregnancy, rubella infection, febrile illness, use of drugs such as thalidomide and retinoic acid, and exposure to organic solvents and lithium [8].
• Patent ductus arteriosus • Atrial septal defect • Ventricular septal defect • Atrioventricular septal defect • Aortopulmonary window • Tetralogy of Fallot • Pulmonary atresia or stenosis • Aortic atresia or stenosis • Mitral atresia or stenosis • Tricuspid atresia or stenosis • Left ventricular outflow obstruction • Coarctation of the aorta | \n\t\t\t• Interrupted aortic arch • Hypoplastic left heart syndrome • d-Transposition of the great arteries • l-Transposition of the great arteries (also known as congenitally-corrected transposition of the great arteries) • Truncus arteriosus communis • Double outlet right or left ventricle • Ebstein’s disease • Anomalies of the coronary arteries • Vascular rings and pulmonary sling • Total or partial anomalous pulmonary venous connection | \n\t\t
Most common types of congenital heart defects.
Mortality occurs mainly in patients with severe forms of CxHD requiring prompt surgical intervention [9]. Interestingly, the relative contribution of the causes of death in patients with CxHD has changed over time. The CxHD causes 3% of all infant deaths and 46% of death from congenital malformations, despite advances in detection and treatment. Arrhythmia followed by congestive heart failure had been considered the main contributing cause of death. However, the mortality figures collected over the past decade showed an increase in myocardial infarction as the cause of death [10]. Until the twentieth century, the majority of newborns with CxHD died because treatment was not available. With the advances made in the field of foetal and paediatric cardiology, survival and quality of life have improved, especially in the past 10–20 years [11].
The advances in paediatric cardiac surgery were accompanied by refinements in extracorporeal perfusion technology that have led to significant improvements in the surgical results during the past decades. Nevertheless, perioperative myocardial damage still remains the most common cause of morbidity and death after a technically successful surgical correction. Despite the importance of this issue, there are a few publications about this. Studies show that the younger the age of patients, the more vulnerable are their myocardium to injury caused by ischemia during definitive repair of congenital heart disease. Therefore, perioperative care for paediatric patients with congenital heart disease needs to take into consideration the dependence of the myocardial damage on age and ischemic time [12]. Others researches have shown that myocardial cell injury in infants submitted to open-heart surgery can be directly associated with varying combinations of gross, microscopic, and histochemical myocardial necrosis in up to 90% of patients who do not survive the perioperative period. The observed alterations within the myocardium can potentially be attributed to the heart defect itself, preoperative hemodynamic instability and its treatment, surgical techniques, cardiopulmonary bypass, myocardial protection strategies, and postoperative medical care.
Furthermore, patients with CxHD are at increased risk of developing myocardial ischemia or premature coronary artery disease (CAD) as the result of: (a) congenital coronary artery abnormalities (e.g., anomalous origin and course of coronary arteries, myocardial bridging, coronary artery fistulas); (b) previous surgery (e.g., arterial switch operation for d-transposition of the great arteries (d-TGA) and surgical coarctation repair); and (c) myocardial ischemia not related directly to coronary artery anomalies but presenting after the atrial switch procedure for TGA (Mustard, Senning) and also in patients with congenitally corrected transposition of the great arteries (ccTGA).
Clinical suspicion is a difficult task, especially in neonates and young infants, in whom the clinical manifestations can be unspecific and transient. In older children and adolescents, chest pain can be present, although myocardial ischemia is rarely the underlying cause [13].
The diagnostic and treatment of paediatric CxHD has undergone remarkable progress over the last 60 years [14]. Moreover, in the past 10 years, significant advancements have been made in foetal echocardiography; in postnatal echocardiography and angiography, leading to greater accuracy in defining the cardiac defect; in interventional catheterization as a palliative or curative measure; and in surgical techniques, which have led to an estimated million adults living today with complex CxHD that required surgery in the neonatal period [15].
In the long term, as a consequence of successful cardiac surgeries in the past decades, there is an increasing number of patients with CxHD reaching adulthood and becoming old. These survivors with complex heart defects are now developing problems associated with aging. The association of CxHD, heart surgeries, and chronic coronary artery disease is not well studied yet [16]. It is possible that these patients are at an increased risk of myocardial ischemia, but epidemiological studies are needed to answer to this question.
Therefore, perioperative myocardial injury is a major determinant of cardiac dysfunction after operations for CxHD. It is very important detect and evaluate the degree of myocardial injury as soon as possible after the operative procedure. Thus in an attempt to clarify possible mechanisms involved in the development of ischemic heart disease in children with CxHD, this study aims to describe the pathological alterations observed in different types of CxHD in the heart of infants submitted to surgical correction of cardiac malformations, and to discuss potential strategies to prevent them.
In normal conditions, an uninterrupted flow of large quantities of oxygenated blood to the myocardium is critical to its normal function [17]. During the systole, this flow can be abolished or even reversed towards the epicardial vessels. The blood must flow from low to high intra-myocardial pressure, in order to meet the metabolic demands of each layer. Such flow must be regulated in such way that areas of high demand can immediately increase their blood supply.
The myocardium extracts about 60 to 75% of oxygen from the blood that passes through it. Because of this high level of extraction, coronary sinus blood has low oxygen tension, generally around 25–35 mm Hg. This low level of oxygen tension requires that any increase in oxygen demand be met by an increase in blood flow rather than an increase in extraction [17].
There are two main mechanisms by which myocardial ischemia can occur: (a) a reduction in myocardial supply of oxygen, and (b) an increase in myocardial oxygen demand [18]. The first situation can occur as a result of reduced coronary blood flow or reduced oxygen content despite normal coronary flow. A reduced coronary blood flow can result from congenital malformations of the coronary arteries, acquired coronary diseases, and also postoperative states, especially after surgical reimplantation of the coronary arteries. Examples of reduced oxygen content in coronary blood include cyanotic heart diseases, severe anaemia, and hemoglobinopathies. The second mechanism can occur in the presence of hypertrophic cardiomyopathy or vigorous exercises. The main diagnoses related to myocardial ischemia are summarized in Table 2.
\n\t\t\t\t | \n\t\t|
• Anomalous coronary arteries | \n\t\t|
\n\t\t\t | • Left main coronary artery from the pulmonary artery • Left main coronary from the right coronary cusp • Right coronary artery from the left coronary cusp | \n\t\t
• Coronary artery fistula • Coronary artery spasm • Thromboembolic or embolic coronary artery disease • Kawasaki disease • Coronary artery dissection • Ostial coronary artery disease status post surgical reimplantation | \n\t\t|
\n\t\t\t | • d-Transposition of the great arteries (d-TGA) arterial switch • Aortic root replacement • Ross procedure | \n\t\t
• Intramyocardial bridging | \n\t\t|
\n\t\t\t\t | \n\t\t|
• Hypertrophic cardiomyopathy • Severe aortic stenosis • Dilated cardiomyopathy • Tachycardia in the face of limited coronary blood flow | \n\t\t|
\n\t\t\t\t | \n\t\t|
• Severe hypoxia or cyanosis | \n\t\t
Diagnosis related to myocardial ischemia.
A number of conditions can lead to myocardial ischemia, including prenatal and birth conditions, the anatomic defect, pre- and postoperative care, surgical technique, and myocardial protection during CPB. These conditions will be discussed in detail below.
Foetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of foetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation [19]. However, although “normal” hypoxia (lower oxygen tension in the foetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes foetal programming of abnormality in the heart’s development. The altered expression patterns of cardioprotective genes likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life [19].
In addition, myocardial dysfunction is a frequent sequel of perinatal asphyxia, resulting from hypoxic-ischemic damage to the myocardium. It can lead to decreased perfusion, tachycardia, hypotension, and need for inotropic support [20,21]. As a consequence, hemodynamic impairment can develop and the myocardium may suffer additional ischemic insults. Infections, need for cardiopulmonary resuscitation, mechanical ventilation, preterm birth, among other factors may also contribute to myocardial damage during this period.
Many CxHD are associated with anomalies such that the child is prone to myocardial ischemia even after uncomplicated delivery and good hemodynamic conditions. They involve congenital anomalies of the coronary arteries and hypertrophic cardiomyopathy. Other diseases can present early in life with congestive heart failure, circulatory shock, or severe hypoxemia. All these factors can compromise coronary circulation and lead to myocardial ischemia.
The entire blood flow to the myocardium comes from two main coronary arteries that arise from the right and left aortic sinuses of Valsalva. In 69% of the population, the right coronary artery is dominant [18]. Although there are normal variations for the coronary anatomy, a comprehensive discussion of this topic is beyond the scope of this chapter, which will focus only on the clinically significant anomalies.
The most common anomaly, accounting for about one third of all major coronary arterial anomalies, is origin of the left circumflex coronary artery from the right main coronary artery. However, this anomaly is rarely of clinical significance. Less common, the origin of the left coronary artery from the right sinus of Valsalva, is of greater significance, and was associated with sudden death in children during or just after vigorous exercise when the vessel passes between the two great arteries [18].
A single coronary artery may be observed in 5–20% of major coronary anomalies. About 40% of these anomalies are associated with other cardiac malformations, including d-TGA, tetralogy of Fallot, ccTGA, double-inlet left ventricle, double-outlet right ventricle, truncus arteriosus, coronary-cameral fistulas, and bicuspid aortic valve [18]. Only a small number of premature deaths have been reported with this anomaly.
When the coronary arteries (either right or left) have their origins in inappropriate sinus, the mechanism of ischemia and death involves an increase in myocardial oxygen demand during exercise that, in turn, causes increases in systolic blood pressure and aortic root distension. If part of the anomalous artery runs within or adjacent to the aortic wall, it may be stretched, compressed, or both, leading to insufficient coronary blood flow.
Other rare coronary anomalies include coronary atresia, stenosis or atresia of a coronary ostium, all coronary arteries from pulmonary artery, left anterior descending coronary artery from pulmonary artery, left circumflex coronary artery from the pulmonary artery or branches, right coronary artery from pulmonary artery, myocardial bridges, etc.
In this anomaly the left coronary artery arises from the pulmonary artery. Therefore, after birth, the left ventricle is perfused with desaturated blood in a regimen of low pressures. The left ventricle becomes then hypoxic, and collaterals start to develop. The left ventricle vessels then dilate to reduce their resistance and increase flow, but this is often not enough to prevent ischemia with compromise of the left ventricular function. This leads to congestive heart failure that can be worsened by mitral regurgitation. With time, the collaterals between right and left coronary artery enlarge until the collateral flow tends to reverse in the left coronary and ultimately into the pulmonary artery. The left-to-right shunt is usually not significant [18,22].
This anomaly is usually isolated but can be associated with patent ductus arteriosus, ventricular septal defect, tetralogy of Fallot, or coarctation of the aorta [18].
In this disease, a hypertrophied right ventricle is always present, with a high oxygen demand to overcome the outflow tract obstruction and provide pulmonary blood flow. In face of severe cyanosis, hemodynamic impairment, the oxygen supply may not balance the high requirements of the right ventricle, leading to myocardial ischemia.
In this disease, the absence of anterograde blood flow across the pulmonary valve associated with the absence of a ventricular septal defect precludes the development of the right ventricle, which becomes hypoplastic. A network of vascular channels, called sinusoids, then develops, communicating the right ventricular cavity with one or both of the coronary arteries.
With systemic or supra-systemic systolic pressure within the right ventricular cavity, blood flow in these fistulous connections may compete with the normal coronary blood flow originating in the ascending aorta. Sometimes, these competing blood coronary streams may cause tortuosity, severe intimal proliferation with obstruction, such that portions of the myocardium may be dependent on the right ventricle-originated coronary flow (so-called right ventricle-dependent coronary circulation) [23]. This portion of the myocardium would then be perfused with unsaturated blood. If these sinusoids are not diagnosed properly, a pulmonary valvotomy can be catastrophic, since the sudden fall in right ventricle pressure will reflect in a dramatic fall in coronary pressure, leading to acute myocardial ischemia and, potentially, death.
Children with a large patent ductus arteriosus with left-to-right shunt, those with severe aortic regurgitation, and those with hypoplastic left heart syndrome, among others, are at great risk for myocardial ischemia, especially in the presence of severe hypoxemia or hypotension. A large patent ductus arteriosus with significant left-to-right shunt can decrease the diastolic pressure in the aorta, significantly diminishing coronary blood flow. A severe aortic regurgitation can lead the same deleterious consequences in diastolic pressure. In patients with hypoplastic left heart syndrome, the ascending aorta receives a retrograde poorly oxygenated blood flow originated from a patent ductus arteriosus. Therefore, these patients are particularly sensitive to hypotension, severe hypoxemia, imbalances between pulmonary and systemic blood flows, and a claudicating ductus arteriosus.
In patients with ccTGA, the right ventricle supports the systemic circulation and can become dilated and hypertrophied with time. Once ventricular dilation and hypertrophy settle in, the blood supply through a normal right coronary artery can become insufficient to meet the increased metabolic demands of the systemic right ventricle [24,25], leading to further ventricular dysfunction. The latter may also have a deleterious effect on left ventricular perfusion, ultimately leading to left ventricular dysfunction [24]. Hypertrophy can also develop in many other situations, especially aortic stenosis and chronic systemic hypertension.
Preoperative care is of special interest in neonates and young infants because usually the CxHD manifests as a critical illness. The neonatal myocardium is less compliant than that of the older child, is less tolerant to increases in afterload, and is less responsive to increases in preload. In the other hand, despite being more labile, this age group is more resilient to metabolic or ischemic injuries, which can play a relative protective role [17]. After birth, neonates with CxHD can deteriorate their hemodynamic status requiring prompt interventions. The higher metabolic rate and oxygen consumption of the neonate account for the rapid appearance of hypoxemia in this age group. In addition, undiagnosed infants and older children may present in shock, congestive heart failure, severe hypoxemia, severe arrhythmia with hemodynamic impairment, or a combination of them, also requiring immediate intensive care. This highly specialized care requires careful evaluation of the structure and function of the heart, the transitional neonatal circulation, and the secondary effects of the defect on other organ systems. All efforts need to be put on making a definitive, precise diagnosis, so appropriate therapeutic measures can be started [17].The treatment of the newborn or infant with severe hemodynamic compromise often involves the use of catecholamines that, despite improving myocardial contractility, can further increase the myocardial metabolic rate and oxygen consumption. Therefore, the attending clinician shall be aware that these drugs need to be used only at the minimum effective dose to obtain the desired effect. Alternatively, when the renal function is preserved, milrinone and levosimendan are very good options, since they can increase myocardial contractility without increasing metabolic rate and oxygen consumption.
Special attention shall be put also on coronary blood flow. Careful monitoring with continuous electrocardiography, as well as serially measuring CK-MB and cardiac troponins, is mandatory for the child with severe hemodynamic impairment, and prompt interventions need to be done quickly in face of a suspected or confirmed coronary insufficiency.
In older patients, the CxHD usually present as congestive heart failure or arrhythmias, not requiring critical care before surgery. There are, obviously, exceptions that shall be properly managed.
In this malformation, a number of different patterns of coronary anatomy have been described. Since the arterial switch operation includes the transfer of the coronary arteries along with the aortic root, it is important that the surgeon knows exactly what the anatomy is. There are at least nine anatomic variations in the way the two coronary arteries arise from the native aorta. Some coronary patterns are more difficult to transfer than others. In 60% of cases, the coronary arteries come from their appropriate sinuses and branch normally. However, the presence of a ventricular septal defect or side-by-side great vessels should alert the cardiologist to an increased likelihood of coronary anomalies, like left circumflex coronary artery arising from the right coronary artery, or inversion of the coronary arteries origin [18,23].
In this disease, the surgical repair includes patch-closure of the ventricular septal defect and widening of the right ventricular outflow tract by infundibular muscle resection combined with either a patch placement across the pulmonary valve annulus or use of a prosthetic conduit from the right ventricle to the pulmonary artery. There are some aberrant coronary patterns associated with tetralogy of Fallot. In some cases, there may be a large conus branch or an accessory left anterior descendent artery running across the face of the right ventricular outflow tract that may be inadvertently damaged during surgery, leading to myocardial ischemia [23].
Recent advances in surgical techniques, myocardial preservation and postoperative care have resulted in complete repair of many CxHD in the neonatal period or early infancy. On the other hand, several investigators have reported that immature myocardium in the paediatric heart is more vulnerable to surgically-induced injury than mature myocardium in the adult heart, due to different structural and functional characteristics [26].
It is widely accepted that the immature heart has a greater tolerance to ischemia than the adult or mature heart. However, most of this laboratory data has been obtained with normal hearts. It is unclear what the ischemic tolerance is when there are pre-existing conditions such as cyanosis, hypertrophy, or acidosis. Many of these conditions may be present in neonates and infants who require surgical correction of their heart defect and may compromise myocardial protection [26].
Newer surgical techniques are being developed to allow for total correction of many CxHD, while limiting the time spent on continuous CPB or in deep hypothermia with circulatory arrest [27]. Therefore, surgeries have been the choice of management in these patients. However, there is a significant procedural- and anaesthesia-related morbidity and mortality in patients with CxHD who undergo repeated surgical interventions [28,29].
Despite of the potentially detrimental side effects of CPB, this technique is still an essential assisting method for open-heart surgery [30]. CPB is a primary circulatory support technique to cardiac surgery in neonates and infants and remains one of the most important factors associated with postoperative mortality and morbidity in open-heart surgery. With improvements in equipment and techniques, CPB has become safer and more reliable. However, it causes profound alterations in physiological fluid homeostasis [31]. The age and size of the patient, the underlying cardiac pathology, and the type of surgical techniques influence what perfusion methods are chosen and the construction of the CPB circuit [32]. Despite significant improvements, CPB remains a non-physiological procedure. The effects of hypothermia, altered perfusion, hemodilution, acid-base management, embolization, and the systemic inflammatory response have been challenging, particularly for neonates and infants. These challenges are primarily related to the smaller circulatory volume, the immaturity of most organ systems, and the increased capillary membrane permeability of neonates and infants [32,33]. Moreover, cardiomyocytes can be affected by hypoxic conditions, and the ischemic effects can induce rapid or gradual changes in the membrane systems that cause reversible or irreversible injury [34]. Experimental studies of myocardial ischemia and reperfusion have established that reperfusion also has negative consequences during circulatory interruption [35,36]. Due to the necessary interruption in coronary circulation required by nearly all cardiac surgeries, the potential for reperfusion damage is significant. If a reperfusion injury does occur, the initial damage may contribute to the impaired cardiac performance that develops immediately after surgery that may then lead to myocardial fibrosis [37,38].
Myocardial preservation during surgically induced myocardial ischemia has been the subject of hundreds of publications in recent years. The most used technique is hypothermic cardioplegia. The consequences of incomplete myocardial protection during surgically induced myocardial ischemia can have a dominant effect on the postoperative course, including low cardiac output, elevated atrial filling pressures, and requirements for increased inotropic support [39]. Cardioplegic solutions are used by most surgeons, and their basic components are potassium (to achieve diastolic arrest) and cold temperature (to reduce the metabolic demands of the heart during ischemia) [39]. There is a variety of different cardioplegic solutions, and there is no consensus on which one is the best. In fact, there is wide variation between institutions regarding cardioplegia and myocardial protection.
Aortic cross clamping during CPB allows the surgeon to intervene on the aortic root, the aortic valve, and the left ventricle outflow tract. However, since during CPB myocardial perfusion is retrograde, during cross clamping the heart is stopped and is not perfused [26,31,39]. Therefore, long cross clamping times are more likely to cause more ischemic injury to the heart.
After surgery, the first 9–12 hours are crucial because during this time the patient will experience a transient decrease in myocardial performance and cardiac output, with increasing need of inotropic support as a consequence of CPB and ischemia-reperfusion injury in the heart and lungs [40]. Besides, the child may deteriorate as a result of residual lesions, pulmonary hypertension, and bleeding. All these factors may lead to poor organ perfusion and hypotension, with consequent reduced coronary blood flow.
In some cases, when the surgical technique involves coronary reimplantation, like the arterial switch for d-TGA, there is a considerable risk of myocardial ischemia. The implantation of the coronary arteries on the neoaorta may be technically challenging, and the coronary insertion may be stenotic or distorted, resulting in insufficient coronary flow. Other causes of insufficient coronary blood flow include spasms of the coronary arteries, air embolism, and thrombosis. Arrhythmias, especially on weaning from CPB, frequently indicate coronary insufficiency; the coronary anastomoses should be promptly investigated before leaving the operating room, as well as transesophageal assessment of left ventricle wall motion. Left ventricular dysfunction may also indicate coronary insufficiency [17].
Many drugs used to improve myocardial contractility and cardiac output can substantially increase myocardial oxygen requirements. In face of hypotension, low cardiac output, or marginally sufficient coronary blood flow, these drugs may actually lead to or aggravate myocardial ischemia. These drugs include dopamine, dobutamine, epinephrine, and norepinephrine.
Arrhythmias, particularly tachyarrhythmias, can also significantly augment the oxygen demand within the myocardium, while compromising the cardiac output, ultimately leading to myocardial ischemia.
Severe blood loss can cause hypotension and a reduction on the arterial oxygen content, substantially affecting oxygen transport to the myocardium.
Chest pain is the hallmark of myocardial ischemia in adults and the elderly. In children and adolescents, however, the great majority of chest pain episodes are of non-cardiac origin [23]. When myocardial ischemia is present in a critically ill patient admitted to an intensive care unit, there may be no specific sign or symptom, and the diagnosis usually need to be made based on ECG findings and biomarkers alone.
The electrocardiogram (ECG) remains the most important diagnostic test in the evaluation for myocardial ischemia. Many factors are involved in the interpretation if the ECG: age, autonomic tone, heart rate, race, gender, and body habitus. Interestingly, pseudo-abnormal ECGs were found in up to 40% of Olympic athletes with structurally normal hearts [13]. It is important to notice that the ECG should be obtained during the episode or shortly after the event whenever possible; otherwise, the alterations in ECG may disappear. The main ECG findings of myocardial ischemia are ST changes, namely elevation or depression of the ST segment. Although repolarization changes, pericardial diseases, drugs, and electrolyte abnormalities can also cause ST changes, a negative ECG is extremely predictive of non-ischemic events [13].
When myocardial ischemia occurs, some enzymes from the myocardium are released and can be detected in peripheral blood approximately 2 hours later. The main biomarkers available are cardiac troponins (both I and T) and creatine kinase MD isoenzyme (CK-MB). When elevated, they can diagnose myocardial ischemia with good sensitivity and specificity [13].
Echocardiography is the predominant imaging modality used for the diagnosis and management of CxHD because of its widespread availability, ease of use, real-time imaging and cost effectiveness. The role of echocardiography specifically for the detection of myocardial ischemia in the CxHD population is less well established. Furthermore, the indications and clinical applications of other newer echo techniques such as tissue Doppler imaging, strain and strain rate imaging, contrast and real-time three-dimensional (3D) echocardiography to detect myocardial ischemia will need to be determined in these patients [2]. It can be helpful to detect the following: hypertrophic cardiomyopathy, severe aortic stenosis, and dilated cardiomyopathy, all of them potentially associated with coronary flow abnormalities and myocardial ischemia. In some cases, it can show clues to the suspicion of ALCAPA and other coronary abnormalities [13].
The diagnosis of chronic ischemia in patients with CxHD may be challenging for the physician because this population, often adults operated on early in life, may have pre-existing anatomic, functional, or electrocardiographic abnormalities. They may also have pre-existing coronary disease that, in association with other environmental, metabolic and genetic factors, may increase the risk of coronary insufficiency. However, discussing the diagnosis of these abnormalities is beyond the scope of this chapter.
Myocardial infarction is defined by pathology as myocardial cell death due to prolonged ischemia. Cell death is categorized pathologically by coagulation necrosis and/or contraction band necrosis, which usually evolves through oncosis, but can result to a lesser degree from apoptosis. Mallory, et al, 1939, and Lodge-Patch, 1951 described myocardial infarction as a form of coagulation necrosis in which cells transform into eosinophilic hyaline masses [41,42]. Other types of necrosis are also quite common in myocardial infarction. The term contraction band necrosis [43] have been used to describe degenerative changes of myocardial fibers characterized by a hypercontraction or spasm of the fibers, with the formation of irregular abnormal transverse bands due to compression of adjacent sarcomeres. These changes have been observed in association with electric shock, deficiency of potassium, administration of catecholamines, coronary arterial reperfusion, and death after cardiac surgery [44,45]. Although the primary event leading to the formation of “contraction bands” is unknown, most often they probably develop in areas of reflow [46] or “twilight blood flow” after ischemia [47].
Colliquative myocytolysis, have been used to describe focal lesions, mainly in the subendocardium and in perivascular regions, which were characterized by progressive vacuolization of fibers with lysis of contractile elements until only empty sarcolemmal tubes remain [48]. Schlesinger and Reiner, 1955 have proposed that focal myocytolysis is a result of metabolic imbalances secondary to a large variety of disorders. In contraction band necrosis and colliquative myocytolysis, healing is thought to occur by fibroblastic proliferation, without the usual sequence of changes that occurs with coagulation necrosis. Careful analysis of histologic sections by an experienced observer is necessary to distinguish these entities [49] (Fig. 1).
Myocardial injuries observed in infants submitted to cardiac surgery with cardiopulmonary bypass. The histopathology of myocardial injuries observed in infants with congenital cardiac heart disease submitted to surgery with cardiopulmonary bypass (CPB).
Myocardial injury in association with cardiac surgery can be caused by different mechanisms, including direct trauma by sewing needles, focal trauma from surgical manipulation of the heart, global ischemia from inadequate perfusion, myocardial cell protection or anoxia, and other complications of the procedure [49]. Cardiac surgery with CPB is frequently associated with postoperative organ dysfunction [50]. Paediatric patients are particularly prone to these complications, and oxidative stress seems to contribute to CPB related postoperative complications. Early systemic oxidative stress could also have been a consequence of ischemia-reperfusion injury to the myocardium [51]. It is recognized that acute stress episodes can induce heart injury that results in the release of cytosolic enzymes and catecholamines to the blood [52,53]. Although catecholamines play an important role in normal cardiac function [54], the use of CPB in cardiac surgery leads to a significant increase in circulating catecholamine levels [55,56] and this excessive release is responsible for the development of various cardiac dysfunctions, e.g. in cardiac remodelling following acute myocardial infarction [54], myocyte death in heart failure [57,58], and myocardial infarction [59]. In a recent study, Oliveira, et al, 2011 described that multifocal areas of myocardial injury seem to be the cause of heart failure for infants who do not survive beyond the perioperative period [60]. They were described in patients submitted to surgery for CxHD with and without CPB, and in patients who died from CxHD prior to surgical intervention. Most of the infants who had undergone surgery with CPB showed important areas of contraction band necrosis and dystrophic calcification. Whereas infants who had undergone surgery without CPB showed coagulation necrosis and healing, suggesting ischemia as the main cause. Importantly, 4-hydroxinonenal (4-HNE), a marker of lipid peroxidation, was strongly expressed, especially in irreversible myocardial lesions. This finding suggests that 4-HNE may be the predominant oxidative stress mechanism that occurs in these patients.
CPB and cardioplegic arrest remain the most popular techniques in clinical intervention during open-heart surgery. However, both can directly or indirectly result in cardiac morbidity following surgery [61]. Cardioplegic arrest renders the heart globally ischemic and, upon reperfusion, triggers myocardial injury [62]. The use of CPB and cardioplegic arrest during cardiac surgery also leads to desensitization of myocardial β-adrenergic receptors (β-ARs) and impaired signalling through this pathway, which is critical in the regulation of cardiac function [63,64]. Previous studies have demonstrated that cardiac β-AR signalling is impaired after CPB with cardioplegic arrest in children with acyanotic heart disease who underwent cardiac surgery [56]. Adrenergic receptors (ARs), first described by Ahlquist, 1948, belong to the superfamily of membrane proteins that activate heterotrimeric guanine nucleotide (G) binding proteins [65]. The heart expresses both β and α1 adrenergic receptors [66]. The effect of β-adrenergic receptor activation is well established: the increase of both heart rate and force of contraction. The effect of α1-receptor activation is more complex. It is usually described as a biphasic or a triphasic effect: initial positive inotropy, followed by a transient negative and finally a more sustained positive inotropy without effect on chronotropy [67]. In the heart, agonist occupancy of β-ARs leads to the primary activation of the adenylyl cyclase (AC) stimulatory G protein (Gs), which leads to increases in intracellular cAMP and protein kinase A (PKA) activity [68]. Alterations in adrenergic signalling are important in a number of cardiac diseases. Undoubtedly, the alterations that take place in the β-AR system during the progression of heart failure (HF) are the most well characterized [68].
A primary mechanism of β-AR desensitization following prolonged stimulation is phosphorylation of agonist-occupied receptors by G protein-coupled receptor kinase-2 (GRK2), a member of the family of serine-threonine kinases known as G protein-coupled receptor kinases [69]. GRK2 has been shown to be important in the modulation of cardiac function in vivo [70,71] and enhanced activity leads to uncoupling of β-ARs and impaired ventricular systolic and diastolic function.
Bulcao, et al, 2008 also found significant uncoupling of β-ARs from adenylyl cyclase under basal conditions and following β-agonist stimulation in a patient population following CPB and arrest [72].
In animal studies, inhibition of GRK2 has led to improved myocardial function after ischemic injury [73]. Myocardial GRK2 activity is known to be elevated in patients with chronic heart failure by approximately 2-3-fold compared to normal controls leading to impaired signalling through β-ARs and blunted inotropic reserve [74]. This is thought to be an important mechanism in the pathogenesis of chronic heart failure resulting from an increase in circulating catecholamines [75].During myocardial ischemia, there is a decrease in the supply of oxygen and nutrients to the heart [62]. This, in turn, provokes a fall in energy production by the mitochondria, which is quickly followed by abnormal accumulation and depletion of several intracellular metabolites (e.g. a fall in adenosine triphosphate (ATP) and a rise in lactate). These metabolic changes lead to a decrease in intracellular pH and an increase in the intracellular concentrations of sodium and Ca2+, which further consumes ATP [76], moreover, a local metabolic release of large amounts of noradrenaline occurs [77,78] together with an increased density of β-adrenergic receptors [79-81]. Consecutively, the capacity of β-adrenergic agonists to stimulate adenylate cyclase activity is enhanced during the first 15 minutes of ischemia [79].
With progressive ischemia, however, isoproterenol-stimulated activity of adenylate cyclase decreases to below the control value, although the density of β-receptors remains elevated [80]. This dissociation of receptor number and functional activity has been found in different models of cardiac ischemia [81], including the isolated perfused rat heart [79], and in human myocardium subjected to hypoxia during cardiopulmonary bypass surgery [56].
Similarly, heart failure in humans has also been characterized by specific alterations in the AR signalling system [82]. The enhanced desensitization of myocardial ARs is likely due, at least in part, to the elevated expression of GRK-2 present in human failing heart [74,83]. Mouse models of severe heart failure have been used to demonstrate that inhibition of GRK-2 with a peptide inhibitor can prevent agonist-stimulated desensitization of cardiac β-ARs. This is sufficient to increase mean survival, reduce dilation, and improve cardiac function. This may represent a novel strategy to improve myocardial function in the setting of compromised heart function [70].
Prevention of myocardial ischemia in the setting of CxHD is an enormous task. Given the complex pathophysiology, it is very unlikely that a single intervention will show significant reductions on the incidence of myocardial ischemia in patients with CxHD. We can, though, comment on a few of issues that have been matter of investigation recently.
The rate of CxHD that are diagnosed before birth is still low, especially in developing countries, where foetal echocardiography is not widely available. Babies with a prenatal diagnostic of CxHD may benefit from catheter-based interventions such as balloon valve dilations or device-closure of abnormal communications. These interventions may lead to better intra-uterus myocardial perfusion and development.
Babies with CxHD should ideally be delivered in a tertiary-care hospital with a dedicated cardiac paediatric intensive care unit. However, this can only be accomplished by increasing prenatal diagnostic of CxHD, which is known to be limited. Babies with a prenatal diagnostic of CxHD that are delivered in an adequate setting are more likely to receive high quality care and less likely to develop hemodynamic instability and myocardial ischemia.
In addition, a precise anatomic diagnosis is mandatory for an adequate preoperative management, and can help clinical decision making on drugs and dosing, oxygen supplementation, and need for mechanical ventilation.
Only a few episodes of myocardial ischemia occurring during surgical procedures can be attributed to the procedure itself. When the procedures involve repositioning of the coronary arteries, special attention should be put on the technique, but other factors may be equally important. Minimizing the duration of CPB and aortic cross clamping can also help reducing periods of myocardial ischemia. In particular, the type of cardioplegia and myocardial protection may substantially affect the likelihood of ischemia both during and after surgery. Some authors defend that blood cardioplegia may be superior to crystalloid cardioplegia especially for longer (> 1 hour) myocardial ischemic time [26]. However, the superiority of one type of cardioplegic solution over the others is still matter of debate.
Immediately after surgery and within the first 24–48 hours, some strategies may significantly reduce the risk of myocardial ischemia following heart surgery, such as: (a) use of coronary vasodilators, like nitroglycerin, especially when the coronary arteries were surgically repositioned; (b) avoiding hypotension; (c) avoiding hyperthermia; (d) minimizing the use of drugs that increase myocardial oxygen demand; (e) keeping the haemoglobin content in blood of at least 10 g/dL; and (f) avoiding tachycardia and aggressively treating tachyarrhythmias. In the setting of hyperthermia, tachyarrhythmias, or low cardiac output syndrome, a mild hypothermia may result in lower oxygen requirements and lower heart rates with better diastolic filling and improved cardiac output.
Preventive measures for coronary disease in the long term in patients with CxHD are not different from the general population. Dyslipidaemias, chronic arterial hypertension, diet, exercise, are diabetes, among others, shall be managed accordingly. Screening for coronary disease and myocardial ischemia should probably be more frequent and comprehensive in people with CxHD but, to date, there is no additional recommendation for these people in order to prevent coronary disease in the adulthood.
Results of paediatric heart surgery have improved through evolution of surgical techniques, CPB, and paediatric cardiac intensive care over the last several years. These efforts are the result of the collaboration of all subspecialties involved in the care of paediatric patients with CxHD. Despite these advances, the field of paediatric cardiac intensive care is still an exciting, demanding, and evolving discipline, necessitating the ongoing commitment of various disciplines to pursue a greater understanding of disease processes and how to best go about treating them [84].
However, it is very important detect and evaluate the degree of myocardial injury as soon as possible after the operative procedure, in an attempt to clarify possible mechanisms involved in the development of ischemic heart disease in children with CxHD, aiming to discuss potential strategies of the prevent this disease [85].
Future research should focus on molecular mechanisms of myocardial injury, including ischemia-reperfusion injury and the systemic inflammatory response. Clinical trials comparing different myocardial protection strategies and anti-inflammatory drugs are strongly needed. In addition, individualized care based on genetic profiles and the presence of polymorphisms may also contribute to better outcomes.
In conclusion, myocardial ischemia following paediatric heart surgery for CxHD is an important issue, probably under diagnosed by physicians, which can lead to catastrophic consequences shortly after surgery or in the long term. The number of people with CxHD reaching adulthood is increasing, and knowing the number of patients with CxHD who were born, who are still alive, and who are reaching adulthood at any given time is required for the adequate allocation of care. These patients are at an increased risk of chronic coronary artery disease and myocardial ischemia. A better understanding of the underlying pathophysiology and the development of screening tests and prophylactic and therapeutic interventions deserve special attention from physicians and researchers.
This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP (2010/11.209-0). Simone G. Ramos is a researcher from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The authors thank Elaine Medeiros Floriano for technical assistance.
Presently, researchers are paying considerable attention to devise eco-friendly approaches for organic transformations. There has been a significant hike in interest among the scientists for more environmentally acceptable processes in the chemical industries. Synthetic chemistry has led us to the development of more potent structural analogs of natural products. The high therapeutic efficiency, bioavailability, and pharmacological characteristics of synthetic molecules have increased their use in medicinal chemistry as compared to natural products. Pharmaceutical chemistry encompasses the design, synthesis, and evaluation of compounds. In designing drugs, there is an upsurge demand for eco-benign pathways to accomplish the green aspects of chemistry. Novel green pathways play a vital role in the synthetic chemistry field by eradication of harmful solvents and chemicals or suitable handling of waste materials. The quest for new and proficient approaches for the synthesis of numerous biologically active scaffolds has made click chemistry a promising approach in chemistry. Click chemistry is a fruitful approach for the fabrication of molecules.
Huisgen and co-workers demonstrated a click reaction, Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). The advanced use of this reaction and click chemistry was introduced by K. Barry Sharpless in 2001. The term click chemistry not only refers to the reaction which occurs fast but also to those that involve twelve principles of green chemistry
According to Sir John Cornforth, a Noble Prize laureate in chemistry in 1975, ideal reaction has been defined as “The ideal chemical process is that which a one-armed operator can perform by pouring the reactants into a bath-tub and collecting the pure product from the drain hole” [16]. Click reactions are designed in such a way that it involves all the twelve principles of green chemistry. Click chemistry includes synthetic methods that are designed to maximize the inclusion of all resources used in the process into the final product. Due to involvement of addition and rearrangement reactions, they have high atom economy. The products are designed with maximum efficacy and minimum cytotoxicity [17]. The green aspects have been depicted in Figure 1.
Green aspects of click chemistry.
Click chemistry includes a cluster of powerful linking chemical reactions that are easy to perform, have high yields, require no or minimal purification, and are flexible in the unification of different structures without the prerequisite of protection steps. Molecular diversity, modularity, and efficiency are essential in synthetic organic chemistry and expected to be involved in the preparation of several complexes and multi-purpose compounds. In general “Click Chemistry” is a class of biocompatible reactions, to link desired substrates with particular biomolecules. Natural products are produced by joining tiny modular units
There is no specific classification of click reactions. The chief requisite for “Click Chemistry” is well met by reactions that take place in nature and their mimic in the laboratory is the closest and most desirable to the mind and spirit of most synthetic organic chemists. Usually, four main classifications of click reactions have been identified [21, 22].
Presently, click chemistry inspired synthesis has become the most fascinating approach. Several multi-component reactions have been designed in an eco-friendly manner like aldol condensation followed by Michael addition, Ugi reaction/aldol reaction, Ugi reaction/Huisgen reaction, Ugi Reaction/Diels-Alder reaction, Ugi reaction/Heck reactions, Michael addition/Mannich reaction, etc. [23]
The most famous click reaction is the classical reaction between an azide and an alkyne. Both the substrates do not react under physiological conditions and go through a cycloaddition reaction only at a particular temperature. The uncatalyzed reaction is usually slow and not regio-selective. On the other hand, it was found that the use of electron-deficient terminal alkynes can cause 1,4-regioselectivity to a great extent. These factors limit the use of uncatalyzed Huisgen cycloaddition as an efficient conjugation pathway [24].
Metals have been used to catalyze several click reactions. The mechanism of metal catalyzed azide alkyne click reaction involves formation of π-alkynyl complex with metal followed by complexation of azide by metal of the π-coordinated triple bond. After cyclization, metallacycle is formed followed by the reductive elimination to afford the relevant 1,2,3-triazole. Several metal like Cu, Ru, Ag, Au, etc. have been employed to accomplish click reactions [25, 26, 27, 28]. This section has been divided in two subsections:
Transition metals have been used to catalyze several organic reactions as they provide large surface area and they have vacant d-orbitals due to which they can show variable oxidation state that help in generation of intermediate for organic synthesis [29, 30]. The common process for the click reaction is the transition metal catalyzed synthesis of 1,2,3-triazoles. 1,3-dipolar cyclo-addition of an azide and an alkyne catalyzed by Cu is the most extensively used click-chemistry pathway due to its high selectivity and simplicity [31]. In 2014, Guo and co-workers synthesized β-cyclodextrin derivatives (1) using mono-6-azidocyclodextrin and aromatic aldehydes by CuI-catalyzed azide–alkyne cyclo-addition. The mono, di, and tri derivatives were synthesized upto 75% yield under mild reaction conditions [32] (Figure 2
Synthesis of β-cyclodextrin derivatives using click chemistry approach.
Later on, Kumar
Synthesis of library of traizole substituted nucleosides.
Tale and co-workers also synthesized 1,2,3-triazoles in excellent yields using (1-(4-methoxybenzyl)-1-
Synthesis of coumarin substituted triazole derivatives.
Yarlagadda
Synthesis of N-((l-benzyl-lH-l,2,3-triazol-5-yl) methyl)-4-(6-methoxy benzo[d]thiazol-2-yl)-2-nitrobenzamide derivatives.
Anand
Synthesis of iso-indoline-1,3-dione linked 1,4 coumarinyl 1,2,3-triazoles derivatives.
Anandhan
Triazole based macrocyclic amides.
Li and co-workers designed triazole derivatives (8 and 9) by click chemistry using CuSO4∙5H2O (0.1 g) and ascorbic acid (0.1 g) in tBuOH/H2O as a solvent and investigated their applications to synthesize self-assembled membrane against copper corrosion. As per the investigation results, it was found that 2-(1-tosyl-1
Derivatives of triazole.
Savanur and co-workers developed facile click chemistry inspired synthesis of triazole ring fused coumarin and quinolinone derivatives using CuSO4 (10 mol%), sodium ascorbate (10 mol%), H2O:PEG, RT followed by K2CO3/DMF at 50–60 °C and examined their anti-microbial activity. Among the synthesized compounds, compounds
Triazole ring fused coumarin and quinolinone derivatives.
Yarovaya
Cytisine conjugated triazole derivative.
Khanapurmath
Methyluracil and theophylline mono-triazole compounds and Bis-triazole compounds.
Green synthesis is the fundamental requirement of present synthetic protocol and use of nanoparticles (Nps) is one of the key tackle for organic transformations. NPs are microscopic particles with dimension between 1–100 nm. These are used as catalysts because they provide large surface area, high catalytic activity, nontoxic, heterogeneous nature, etc. In lieu of this, Chetia
Triazole derivatives.
Chavan
Spirochromenocarbazole tethered 1,2,3-triazole derivatives.
Elavarasan
Structures of different triazole derivatives.
Pourmohammad
Triazole derivatives.
Thanh
Click chemistry has been used to synthesize biologically active hybrids of several synthetic organic molecules. In lieu of this, Sharova
Synthesis of triazole derivatives.
The reaction involved mild reaction conditions, water as a green solvent with low catalyst loading, no need of further purification which made the protocol eco-friendly. Bernard
Synthesis of cyclooctyne and trans-cyclooctene.
Qui
Synthesis of parthenolide–thiazolidinedione and 3’-O-1,2,3-triazolyl-guanosine-5′-
Senthilvelan
Several new metal-free click chemistry assisted syntheses of heterocyclic scaffolds have been designed up to date. These pathways involve a variety of functional group tolerance in the substrate of cyclo-addition reaction. These synthetic pathways can be achieved under mild conditions and give high yields of desired products using organo-catalyst [56, 57]. In 2010, Fokin and co-authors developed the first transition metal-free synthesis of 1,5-diaryl-1,2,3-triazoles (31) employing azide-alkyne cyclo-addition [58] (Figure 19
Metal-free synthetic route of triazole based heterocycles.
In 2018, Han
4-Trifluroacetyl 1,2,3-triazole derivatives.
In the same year, Tan
Visible-light-assisted organic transformations have received a huge response in chemical synthesis in order to design environmentally friendly approaches. The synthesis using economical, easily available visible-light sources have become vanguard in the synthetic chemistry as a prevailing approach for the activation of small molecules to furnish the desired products [64, 65, 66].
Burykina
Visible light assisted synthesis of vinyl sulphide.
Recently, Wu
Ultrasound assisted reactions are milder and faster. The mechanism of ultrasound is based on an acoustic cavitation phenomenon. This technology hastens the reaction in both heterogeneous and homogeneous media, due to amplified energy intake. It shortens the reaction time and augments the competence of the system by triggering the catalyst surface area and removing deposited impurities [69, 70]. A decades ago, Cintas
Synthesis of ultrasound assisted 1-azido-3-chloropropan-2-ol azido chitin derivatives.
The use of microwave irradiation in cyclo-addition reactions for click chemistry has also been comprehensively deliberated. It allows efficient internal heat transfer and therefore decreases the reaction time as well as enhances the reaction rate with high yield [76, 77]. The increased temperature can be used over short periods thus avoiding decomposition or polymerization. Ashok and co-workers demonstrated the synthesis of 1,2,3-triazole analogs using microwave irradiations in 8–10 min and examined their antimicrobial activity [78] (Figure 23
Microwave assisted synthesis of triazole based scaffolds.
In the past two decades, various polymers have been introduced through ionene synthesis, click chemistry, and Michael addition
In 2018, Acik and co-authors demonstrated a simple copper (I)-catalyzed azide-alkyne cyclo-addition “click” reaction for the synthesis of polypropylene-graft-poly(L-lactide) copolymers (PP-g-PLAs) using different feeding ratio of alkyne end-functionalized poly(L-lactide) azide and side-chain functionalized polypropylene in the presence of CuBr/PMDETA and CuAAC [85]. This polymer exhibited special characteristics like good thermal property, wettability and biodegradability.
Öztürk and companions introduced efficient click chemistry inspired synthesis of an amphiphilic copolymer
Poly(CL-co-EG)star-type amphiphilic coploymer.
Yang
Wang
Agrihari
Henning
Synthesis of triazole-based photo-initiators.
A novel, facile and efficient synthesis of 3- and 4-arm star-shaped poly(2-methyl-N-aziridine)s
3-and 4-arm star-shaped poly(2-methyl-N-aziridine)s.
Cai
Tian and companions demonstrated the synthesis of the functionalized poly(1-butene)
Functionalized poly(1-butene) synthesis.
Zhang
Gao
Process able and self-healable polymer synthesis.
Zhu
PTMA-GO polymer synthesis.
Shen
PEGylated PAN membranes.
Synthetic organic chemistry includes the synthesis of biologically active molecules and designing of potent scaffolds. Click chemistry is one of the toolboxes for chemistry, biology, nano, and material sciences. It has vivid applications in the synthesis of organic molecules, polymers, nanoparticles, biosensors, and many more. The concept of click chemistry fulfills the green aspects of a reaction. In this chapter, we have deliberated an incredible flurry of activities in the field of click chemistry inspired synthesis. This study highlights the current advancements in the synthesis of heterocyclic and other cyclic structures using click reactions. The insertion of a triazole ring with the help of click reaction increases the biological activity of the synthesized compounds. Different pathways with metal or metal-free conditions using conventional or non-conventional reaction methods have also been demonstrated in this chapter.
The authors are grateful to the Department of Chemistry, Mohan Lal Sukhadia University, Udaipur (Raj.), India for providing necessary library facilities for carrying out the work. A. Sethiya is thankful to UGC-MANF (201819MANF-2018-2019-RAJ-91971) for providing Senior Research Fellowship to carry out this work. N. Sahiba is very much grateful to CSIR-Delhi (file no. 09/172(0088)2018-EMR-I), New Delhi for providing Senior Research Fellowship as a financial support.
The authors declare no conflict of interest.
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Wireless power transmission (WPT) technology was first pursued by Tesla over a century ago. However, it faced several challenges for deployment in real applications. Recently, energy harvesting and WPT technologies have received much attention as a clean and renewable power source. Rectenna (rectifying antenna) system can be used for remotely charging batteries in several sensor networks at internet of things (IoT) applications as commonly used in smart buildings, implanted medical devices and automotive applications. Rectenna, which is used to convert from RF energy to usable DC electrical energy, is mainly a combination between a receiving antenna and a rectifier circuit. This chapter will present several designs for single and multiband rectennas with different characteristics for energy harvesting applications. Single and multiband antennas as well as rectifier circuits with matching networks are introduced for complete successful rectenna circuit models. 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Further, the improved dual circularly polarized (CP) omnidirectional antenna based on slot array in coaxial cylinder structure is presented too, and two ports are assigned in its two side as left hand circularly polarized (LHCP) port and right hand circularly polarized (RHCP) port, respectively. The simulation and experiment results show their novelty and good performance of omnidirectional circular polarization with about 5 dBi gain in 5.2–5.9 GHz.",book:{id:"5427",slug:"modern-antenna-systems",title:"Modern Antenna Systems",fullTitle:"Modern Antenna Systems"},signatures:"Bin Zhou, Junping Geng, Xianling Liang, Ronghong Jin and\nGuanshen Chenhu",authors:[{id:"147056",title:"Prof.",name:"Xian-Ling",middleName:null,surname:"Liang",slug:"xian-ling-liang",fullName:"Xian-Ling Liang"},{id:"189327",title:"Prof.",name:"Junping",middleName:null,surname:"Geng",slug:"junping-geng",fullName:"Junping Geng"},{id:"189923",title:"Prof.",name:"Ronghong",middleName:null,surname:"Jin",slug:"ronghong-jin",fullName:"Ronghong Jin"},{id:"189925",title:"MSc.",name:"Bin",middleName:null,surname:"Zhou",slug:"bin-zhou",fullName:"Bin Zhou"},{id:"189927",title:"MSc.",name:"Guanshen",middleName:null,surname:"Chenhu",slug:"guanshen-chenhu",fullName:"Guanshen Chenhu"}]}],onlineFirstChaptersFilter:{topicId:"762",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},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:107,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:10,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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She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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He is also Member of the Laboratory of genetic, animal and feed resource and member of Animal science Department of INAT. He graduated from Higher School of Agriculture of Mateur, University of Carthage, in 2002 and completed his masters in 2006. Dr. M’HAMDI completed his PhD thesis in Genetic welfare indicators of dairy cattle at Higher Institute of Agronomy of Chott-Meriem, University of Sousse, in 2011. 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Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"95",type:"subseries",title:"Urban Planning and Environmental Management",keywords:"Circular economy, Contingency planning and response to disasters, Ecosystem services, Integrated urban water management, Nature-based solutions, Sustainable urban development, Urban green spaces",scope:"