Factor levels in the experimental design.
\\n\\n
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6592",leadTitle:null,fullTitle:"Green Electronics",title:"Green Electronics",subtitle:null,reviewType:"peer-reviewed",abstract:"The Green Electronics book is intended to stimulate people's thinking toward the new concepts of an environment-friendly electronics - the main challenge in the future. The book offers multiple solutions to push the classical electronic industry toward green concepts, aided by nanotechnologies, with revolutionary features that provide low power consumption in electronics, use biomaterials for integrated structures, and include environmental monitoring tools. Based on organic semiconductors/insulators without toxic precursors, green electronic technologies launched promising devices like OLED, OTFT, or nano-core-shell transistors. The Green Electronics book successfully presents the recent directions collected worldwide and leaves free space for continuing year by year with new subtopics.",isbn:"978-1-78923-305-6",printIsbn:"978-1-78923-304-9",pdfIsbn:"978-1-83881-577-6",doi:"10.5772/intechopen.71456",price:119,priceEur:129,priceUsd:155,slug:"green-electronics",numberOfPages:252,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"9e9601377edfbf1502eab5f0c7baba86",bookSignature:"Cristian Ravariu and Dan Mihaiescu",publishedDate:"June 20th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6592.jpg",numberOfDownloads:13926,numberOfWosCitations:18,numberOfCrossrefCitations:15,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:29,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:62,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 27th 2017",dateEndSecondStepPublish:"November 17th 2017",dateEndThirdStepPublish:"January 16th 2018",dateEndFourthStepPublish:"April 6th 2018",dateEndFifthStepPublish:"June 5th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"43121",title:"Dr.",name:"Cristian",middleName:null,surname:"Ravariu",slug:"cristian-ravariu",fullName:"Cristian Ravariu",profilePictureURL:"https://mts.intechopen.com/storage/users/43121/images/6033_n.jpg",biography:"Cristian Ravariu is full Professor at \\Politehnica\\ University of Bucharest,Romania, Electronic Device and Circuits Department. He received the B.S.(\\'93), Ph.D (\\'01), PostDoc (\\'12) degrees, with specialization stages at Federal Institute of Technology from Lausanne Switzerland, Laboratory for Analysis and Architecture of Systems Toulouse France, and Faculty of Bioengineering from Patras, Greece. He published more than 150 articles, 5 books, 3 chapters. Now he is interested in electron devices, nanoelectronics, green semiconductors and bioengineering. Dr. Ravariu is the current Chairman of the joint Romanian IEEE Chapters of Solid-State Circuits & Electron Devices. Romanian Academy awarded his book from 2010: C. Ravariu - Electronics biodevices: from nanostructures to medical applications. He patented the NOI nanotransistor (Nothing On Insulator) and an integrated biosensor technology.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Polytechnic University of Bucharest",institutionURL:null,country:{name:"Romania"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"221113",title:"Prof.",name:"Dan",middleName:null,surname:"Mihaiescu",slug:"dan-mihaiescu",fullName:"Dan Mihaiescu",profilePictureURL:"https://mts.intechopen.com/storage/users/221113/images/6034_n.jpg",biography:"Dr. Dan Mihaiescu (Ph.D. in Chemistry), is a Professor of Instrumental Analysis and Organic Chemistry, of the Organic Chemistry “Costin Nenitescu” Department, Faculty of Applied Chemistry and Material Science, Polytechnic University Bucharest, Romania. His main areas of interest are related to Organic Chemistry, Instrumental Analysis, Nanotechnology, Plasma Chemistry, Natural Products, Forensic Chemistry, Oceanography, GIS integration of analytical data. Currently his research is focused on the advanced nanocomposite / hybrid materials synthesis (magnetic nanocarriers, core-shell nanoparticles, silica-based mesoporous materials, biocompatible materials, biopolymers), characterization and applications.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"741",title:"Electronic Engineering",slug:"electronic-engineering"}],chapters:[{id:"58755",title:"Introductory Chapter: Green Electronics Starting from Nanotechnologies and Organic Semiconductors",doi:"10.5772/intechopen.73312",slug:"introductory-chapter-green-electronics-starting-from-nanotechnologies-and-organic-semiconductors",totalDownloads:1102,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Cristian Ravariu and Dan Eduard Mihaiescu",downloadPdfUrl:"/chapter/pdf-download/58755",previewPdfUrl:"/chapter/pdf-preview/58755",authors:[{id:"43121",title:"Dr.",name:"Cristian",surname:"Ravariu",slug:"cristian-ravariu",fullName:"Cristian Ravariu"},{id:"221113",title:"Prof.",name:"Dan",surname:"Mihaiescu",slug:"dan-mihaiescu",fullName:"Dan Mihaiescu"}],corrections:null},{id:"60410",title:"Study of Heat Dissipation Mechanism in Nanoscale MOSFETs Using BDE Model",doi:"10.5772/intechopen.75595",slug:"study-of-heat-dissipation-mechanism-in-nanoscale-mosfets-using-bde-model",totalDownloads:906,totalCrossrefCites:6,totalDimensionsCites:12,hasAltmetrics:0,abstract:"In this chapter, we report the nano-heat transport in metal-oxide-semiconductor field effect transistor (MOSFET). We propose a ballistic-diffusive model (BDE) to inquire the thermal stability of nanoscale MOSFET’s. To study the mechanism of scattering in the interface oxide-semiconductor, we have included the specularity parameter defined as the probability of reflection at boundary. In addition, we have studied the effective thermal conductivity (ETC) in nanofilms we found that ETC depend with the size of nanomaterial. The finite element method (FEM) is used to resolve the results for a 10 nm channel length. The results prove that our proposed model is close to those results obtained by the Boltzmann transport equation (BTE).",signatures:"Houssem Rezgui, Faouzi Nasri, Mohamed Fadhel Ben Aissa and\nAmen Allah Guizani",downloadPdfUrl:"/chapter/pdf-download/60410",previewPdfUrl:"/chapter/pdf-preview/60410",authors:[{id:"235600",title:"Dr.",name:"Faouzi",surname:"Nasri",slug:"faouzi-nasri",fullName:"Faouzi Nasri"},{id:"245417",title:"Ph.D. Student",name:"Houssem",surname:"Rezgui",slug:"houssem-rezgui",fullName:"Houssem Rezgui"},{id:"245418",title:"Prof.",name:"Mohamed Fadhel",surname:"Ben Aissa",slug:"mohamed-fadhel-ben-aissa",fullName:"Mohamed Fadhel Ben Aissa"},{id:"245419",title:"Prof.",name:"AmenAllah",surname:"Guizani",slug:"amenallah-guizani",fullName:"AmenAllah Guizani"}],corrections:null},{id:"60365",title:"Advanced Technologies for Large-Sized OLED Display",doi:"10.5772/intechopen.74869",slug:"advanced-technologies-for-large-sized-oled-display",totalDownloads:1842,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Five years have passed, since the first 55″ full high-definition (FHD) OLED TV fabricated on Gen 8.5 glass was successfully launched into the TV market. For the time being, the size of OLED TV became diverse from 55″ to 77″, and the resolution was doubled into ultrahigh definition (UHD). The brightness and color gamut were enhanced, while the lower power consumption was realized. Utmost picture quality and slim form factor of OLED TV as well as the improved performance have made OLED TV recognized as the best premium TV. In this chapter, we describe the recent progress in three key technologies, which enable such an enhancement of performance in OLED TV, i.e., oxide thin-film transistor (TFT) and white organic light-emitting diode (WOLED), compensation circuit, and method to compensate the nonuniformity of oxide TFTs, OLED devices, and luminance.",signatures:"Chang Wook Han, Hong-Seok Choi, Chanki Ha, Hongjae Shin, Hyun\nChul Choi and In Byeong Kang",downloadPdfUrl:"/chapter/pdf-download/60365",previewPdfUrl:"/chapter/pdf-preview/60365",authors:[{id:"11132",title:"Dr.",name:"Chang Wook",surname:"Han",slug:"chang-wook-han",fullName:"Chang Wook Han"},{id:"241122",title:"Dr.",name:"Hong Seok",surname:"Choi",slug:"hong-seok-choi",fullName:"Hong Seok Choi"},{id:"241126",title:"Dr.",name:"Chanki",surname:"Ha",slug:"chanki-ha",fullName:"Chanki Ha"},{id:"241127",title:"Dr.",name:"Hong Jae",surname:"Shin",slug:"hong-jae-shin",fullName:"Hong Jae Shin"},{id:"241132",title:"Dr.",name:"Hyun Chul",surname:"Choi",slug:"hyun-chul-choi",fullName:"Hyun Chul Choi"},{id:"241133",title:"Dr.",name:"In Byeong",surname:"Kang",slug:"in-byeong-kang",fullName:"In Byeong Kang"}],corrections:null},{id:"60276",title:"Conducting Polymers as Elements of Miniature Biocompatible Sensor",doi:"10.5772/intechopen.75715",slug:"conducting-polymers-as-elements-of-miniature-biocompatible-sensor",totalDownloads:1181,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Conducting polymers (CPs), the so-called “fourth generation of polymeric materials”, can solve essential problems in biosensing technologies due to their unique material properties and implementation in innovative device systems. CPs have excellent biocompatibility. They can provide advantageous interfaces for bioelectrodes owing to their hybrid conducting mechanics, combining both electron and ionic charge carriers. Many (i.e. glucose) biosensors use immobilized enzymes to form a selective layer on CP structure. Miniaturization of sensors is a new requirement. Mini sensors are portable and wearable with low utilization of sample and cost-effective technology of production.",signatures:"Joanna Cabaj and Jadwiga Sołoducho",downloadPdfUrl:"/chapter/pdf-download/60276",previewPdfUrl:"/chapter/pdf-preview/60276",authors:[{id:"183516",title:"Dr.",name:"Jadwiga",surname:"Soloducho",slug:"jadwiga-soloducho",fullName:"Jadwiga Soloducho"},{id:"193944",title:"D.Sc.",name:"Joanna",surname:"Cabaj",slug:"joanna-cabaj",fullName:"Joanna Cabaj"}],corrections:null},{id:"60492",title:"Low-Temperature Solution-Processable Functional Oxide Materials for Printed Electronics",doi:"10.5772/intechopen.75610",slug:"low-temperature-solution-processable-functional-oxide-materials-for-printed-electronics",totalDownloads:1065,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Over a decade since the first printed oxide transistor has been reported, printed oxide electronics is now becoming emerging technologies for realization of flexible, large-scale, low-cost electronic devices and systems. This chapter summarizes recent progress in the development of low-temperature solution-processable functional oxide materials and devices, and it also addresses critical challenges for the fundamental understanding and practical implementation of complex oxides in devices. The first part of this chapter gives an overview of the development of functional oxide inks such as semiconductors, conductors, and dielectrics. The second part discusses high-resolution printing technologies and some applications of printed electronics to exemplify their potential.",signatures:"Phan Trong Tue",downloadPdfUrl:"/chapter/pdf-download/60492",previewPdfUrl:"/chapter/pdf-preview/60492",authors:[{id:"233418",title:"Dr.",name:"Trong Tue",surname:"Phan",slug:"trong-tue-phan",fullName:"Trong Tue Phan"}],corrections:null},{id:"59073",title:"Vehicle Dynamics and Green Electronic Differential for eKart",doi:"10.5772/intechopen.72892",slug:"vehicle-dynamics-and-green-electronic-differential-for-ekart",totalDownloads:1372,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Today, electric vehicles are becoming increasingly popular in our lives. In motorsport, however, they are not as widely used. Formula E, which was created to boost electric motorsport, is not enough to popularize it. Every driver who wants to advance to F1 (highest rank racing series) has to start from karting between the ages of 5 and 8. But, today, gokarts are only powered by combustion engines. In order to provide young drivers with the possibility of racing small green electric vehicles, the so-called eKarts, combustion engines have to be replaced with electric motors. eKarts should offer similar performance to combustion engine go-karts. Therefore, to determine the required power of the electric motors and the capacity of the batteries in eKarts for different age categories, the technical parameters of the different age categories of combustion engine racing go-karts were analyzed. In this chapter, the present Li-ion battery technology makes it possible to construct eKarts for children and junior categories. With the current technology, it is not possible to create an eKart for senior categories (15 and over) in line with the current regulations for go-karts. Chance such green electronics solution with torque vectoring will provide better efficiency of energy consumption and lover impact on natural environment in reduced emission of both noise and greenhouse gases.",signatures:"Golebiowski Wlodzimierz, Kubiak Przemysław and Szymon\nMadziara",downloadPdfUrl:"/chapter/pdf-download/59073",previewPdfUrl:"/chapter/pdf-preview/59073",authors:[{id:"225642",title:"M.Sc.",name:"Włodzimierz",surname:"Gołębiowski",slug:"wlodzimierz-golebiowski",fullName:"Włodzimierz Gołębiowski"}],corrections:null},{id:"61248",title:"Ultra-Low-Power Embedded SRAM Design for Battery- Operated and Energy-Harvested IoT Applications",doi:"10.5772/intechopen.76765",slug:"ultra-low-power-embedded-sram-design-for-battery-operated-and-energy-harvested-iot-applications",totalDownloads:1283,totalCrossrefCites:5,totalDimensionsCites:9,hasAltmetrics:0,abstract:"Internet of Things (IoT) devices such as wearable health monitors, augmented reality goggles, home automation, smart appliances, etc. are a trending topic of research. Various IoT products are thriving in the current electronics market. The IoT application needs such as portability, form factor, weight, etc. dictate the features of such devices. Small, portable, and lightweight IoT devices limit the usage of the primary energy source to a smaller rechargeable or non-rechargeable battery. As battery life and replacement time are critical issues in battery-operated or partially energy-harvested IoT devices, ultra-low-power (ULP) system on chips (SoC) are becoming a widespread solution of chip makers’ choice. Such ULP SoC requires both logic and the embedded static random access memory (SRAM) in the processor to operate at very low supply voltages. With technology scaling for bulk and FinFET devices, logic has demonstrated to operate at low minimum operating voltages (VMIN). However, due to process and temperature variation, SRAMs have higher VMIN in scaled processes that become a huge problem in designing ULP SoC cores. This chapter discusses the latest published circuits and architecture techniques to minimize the SRAM VMIN for scaled bulk and FinFET technologies and improve battery life for ULP IoT applications.",signatures:"Arijit Banerjee",downloadPdfUrl:"/chapter/pdf-download/61248",previewPdfUrl:"/chapter/pdf-preview/61248",authors:[{id:"235246",title:"Ph.D. Student",name:"Arijit",surname:"Banerjee",slug:"arijit-banerjee",fullName:"Arijit Banerjee"}],corrections:null},{id:"60223",title:"Optimizing of Convolutional Neural Network Accelerator",doi:"10.5772/intechopen.75796",slug:"optimizing-of-convolutional-neural-network-accelerator",totalDownloads:1900,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In recent years, convolution neural network (CNN) had been widely used in many image-related machine learning algorithms since its high accuracy for image recognition. As CNN involves an enormous number of computations, it is necessary to accelerate the CNN computation by a hardware accelerator, such as FPGA, GPU and ASIC designs. However, CNN accelerator faces a critical problem: the large time and power consumption caused by the data access of off-chip memory. Here, we describe two methods of CNN accelerator to optimize CNN accelerator, reducing data precision and data-reusing, which can improve the performance of accelerator with the limited on-chip buffer. Three influence factors to data-reusing are proposed and analyzed, including loop execution order, reusing strategy and parallelism strategy. Based on the analysis, we enumerate all legal design possibilities and find out the optimal hardware design with low off-chip memory access and low buffer size. In this way, we can improve the performance and reduce the power consumption of accelerator effectively.",signatures:"Wenquan Du, Zixin Wang and Dihu Chen",downloadPdfUrl:"/chapter/pdf-download/60223",previewPdfUrl:"/chapter/pdf-preview/60223",authors:[{id:"233947",title:"Prof.",name:"Dihu",surname:"Chen",slug:"dihu-chen",fullName:"Dihu Chen"},{id:"234308",title:"MSc.",name:"Du",surname:"Wenquan",slug:"du-wenquan",fullName:"Du Wenquan"},{id:"234313",title:"Prof.",name:"Zixin",surname:"Wang",slug:"zixin-wang",fullName:"Zixin Wang"}],corrections:null},{id:"59522",title:"Biomolecules and Pure Carbon Aggregates: An Application Towards “Green Electronics”",doi:"10.5772/intechopen.73177",slug:"biomolecules-and-pure-carbon-aggregates-an-application-towards-green-electronics-",totalDownloads:1033,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"“Green electronics” is a novel scientific term which aims to identify the compounds of natural origin (economically safe and biodegradable) and establish economically efficient route for production of synthetic materials. The purpose of green electronics is to create path for the production of human and environmental friendly electronics and the integration of electronics with living tissue in particular. These researches may help to fulfill not only the organic electronics to deliver low cost energy efficient materials and devices, but also achieve unimaginable functionalities for electronics. In this chapter we have considered the molecular electronic devices biomolecules: deoxyribonucleic acid (DNA) and pure carbon aggregates: (carbon nanotubes (CNTs)/graphene), their properties and applications.",signatures:"Ruby Srivastava",downloadPdfUrl:"/chapter/pdf-download/59522",previewPdfUrl:"/chapter/pdf-preview/59522",authors:[{id:"185788",title:"Dr.",name:"Ruby",surname:"Srivastava",slug:"ruby-srivastava",fullName:"Ruby Srivastava"}],corrections:null},{id:"58957",title:"Integrated p-NOI Structures on Nanoporous Material Designed for Biodetection",doi:"10.5772/intechopen.73175",slug:"integrated-p-noi-structures-on-nanoporous-material-designed-for-biodetection",totalDownloads:1041,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Pesticides are utilized to protect the crops, destroying or controlling any pest. Unfortunately, pesticides pollute the entire environment: plants, organisms, soil, and water. This chapter describes a paraoxon pesticide biosensor that includes nanostructures and porous materials integrated on silicon (Si), as convergent objectives of the green microelectronics strategy. The transducer element is in an interdigitated capacitive electrode that recently highlighted a special nanostructure—the planar nothing on insulator (p-NOI)—included in the capacitive detection system. The biodetection is based on the hydrolysis of the acetylcholinesterase (AChE) enzyme as biosensor receptor. So, the final application is an enzymatic biosensor that utilizes the nanoporous Si layer for the enzyme adsorption, with p-NOI capacitive transducer, for the environmental monitoring.",signatures:"Cristian Ravariu, Elena Manea, Alina Popescu and Cătălin\nPârvulescu",downloadPdfUrl:"/chapter/pdf-download/58957",previewPdfUrl:"/chapter/pdf-preview/58957",authors:[{id:"43121",title:"Dr.",name:"Cristian",surname:"Ravariu",slug:"cristian-ravariu",fullName:"Cristian Ravariu"},{id:"230913",title:"Dr.",name:"Elena",surname:"Manea",slug:"elena-manea",fullName:"Elena Manea"},{id:"230914",title:"Dr.",name:"Alina",surname:"Popescu",slug:"alina-popescu",fullName:"Alina Popescu"},{id:"230915",title:"Dr.",name:"Catalin",surname:"Pirvulescu",slug:"catalin-pirvulescu",fullName:"Catalin Pirvulescu"}],corrections:null},{id:"58653",title:"Environmental Application of High Sensitive Gas Sensors with Tunable Diode Laser Absorption Spectroscopy",doi:"10.5772/intechopen.72948",slug:"environmental-application-of-high-sensitive-gas-sensors-with-tunable-diode-laser-absorption-spectros",totalDownloads:1205,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Due to the fact of global warming, air quality deterioration and health concern over the past few decades, great demands and tremendous efforts for new technology to detect hazard gases such as CH4, CO2, CO, H2S, and HONO have been performed. Tunable diode laser absorption spectroscopy (TDLAS) is a kind of technology with advantages of high sensitivity, high selectivity, and fast responsivity. It has been widely used in the applications of greenhouse gas measurements, industrial process control, combustion gas measurements, medicine, and so on. In this chapter, we will briefly summarize the most recent progress on TDLAS technology and present several kinds of gas sensors developed mainly by our group for various field applications. These could expand from energy, environment, and public safety to medical science.",signatures:"Xiaojuan Cui, Fengzhong Dong, Zhirong Zhang, Hua Xia, Tao Pang,\nPengshuai Sun, Bian Wu, Shuo Liu, Luo Han, Zhe Li and Runqing Yu",downloadPdfUrl:"/chapter/pdf-download/58653",previewPdfUrl:"/chapter/pdf-preview/58653",authors:[{id:"68041",title:"Dr.",name:"Hua",surname:"Xia",slug:"hua-xia",fullName:"Hua Xia"},{id:"69003",title:"Prof.",name:"Fengzhong",surname:"Dong",slug:"fengzhong-dong",fullName:"Fengzhong Dong"},{id:"232345",title:"Dr.",name:"Xiaojuan",surname:"Cui",slug:"xiaojuan-cui",fullName:"Xiaojuan Cui"},{id:"232347",title:"Dr.",name:"Zhirong",surname:"Zhang",slug:"zhirong-zhang",fullName:"Zhirong Zhang"},{id:"232348",title:"Dr.",name:"Tao",surname:"Pang",slug:"tao-pang",fullName:"Tao Pang"},{id:"232349",title:"Dr.",name:"Pengshuai",surname:"Sun",slug:"pengshuai-sun",fullName:"Pengshuai Sun"},{id:"232350",title:"Dr.",name:"Bian",surname:"Wu",slug:"bian-wu",fullName:"Bian Wu"},{id:"232351",title:"Mr.",name:"Luo",surname:"Han",slug:"luo-han",fullName:"Luo Han"},{id:"232354",title:"BSc.",name:"Shuo",surname:"Liu",slug:"shuo-liu",fullName:"Shuo Liu"},{id:"232355",title:"BSc.",name:"Zhe",surname:"Li",slug:"zhe-li",fullName:"Zhe Li"},{id:"232356",title:"BSc.",name:"Runqing",surname:"Yu",slug:"runqing-yu",fullName:"Runqing Yu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3333",title:"Micro Electronic and Mechanical Systems",subtitle:null,isOpenForSubmission:!1,hash:"587c603004cde573fc9fca7baef0c060",slug:"micro-electronic-and-mechanical-systems",bookSignature:"Kenichi Takahata",coverURL:"https://cdn.intechopen.com/books/images_new/3333.jpg",editedByType:"Edited by",editors:[{id:"4541",title:"Prof.",name:"Kenichi",surname:"Takahata",slug:"kenichi-takahata",fullName:"Kenichi 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"79787",slug:"corrigendum-graves-disease",title:"Corrigendum: Graves’ Disease",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/79787.pdf",downloadPdfUrl:"/chapter/pdf-download/79787",previewPdfUrl:"/chapter/pdf-preview/79787",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/79787",risUrl:"/chapter/ris/79787",chapter:{id:"75553",slug:"graves-disease-clinical-significance-and-management",signatures:"Thenmozhi Paluchamy",dateSubmitted:"December 3rd 2020",dateReviewed:"February 4th 2021",datePrePublished:"July 14th 2021",datePublished:"December 1st 2021",book:{id:"10312",title:"Graves' Disease",subtitle:null,fullTitle:"Graves' Disease",slug:"graves-disease",publishedDate:"December 1st 2021",bookSignature:"Robert Gensure",coverURL:"https://cdn.intechopen.com/books/images_new/10312.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"16515",title:"Dr.",name:"Robert",middleName:null,surname:"Gensure",slug:"robert-gensure",fullName:"Robert Gensure"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"296190",title:"Dr.",name:"Thenmozhi",middleName:null,surname:"Paluchamy",fullName:"Thenmozhi Paluchamy",slug:"thenmozhi-paluchamy",email:"thenmozhi.sethu@gmail.com",position:null,institution:null}]}},chapter:{id:"75553",slug:"graves-disease-clinical-significance-and-management",signatures:"Thenmozhi Paluchamy",dateSubmitted:"December 3rd 2020",dateReviewed:"February 4th 2021",datePrePublished:"July 14th 2021",datePublished:"December 1st 2021",book:{id:"10312",title:"Graves' Disease",subtitle:null,fullTitle:"Graves' Disease",slug:"graves-disease",publishedDate:"December 1st 2021",bookSignature:"Robert Gensure",coverURL:"https://cdn.intechopen.com/books/images_new/10312.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"16515",title:"Dr.",name:"Robert",middleName:null,surname:"Gensure",slug:"robert-gensure",fullName:"Robert Gensure"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"296190",title:"Dr.",name:"Thenmozhi",middleName:null,surname:"Paluchamy",fullName:"Thenmozhi Paluchamy",slug:"thenmozhi-paluchamy",email:"thenmozhi.sethu@gmail.com",position:null,institution:null}]},book:{id:"10312",title:"Graves' Disease",subtitle:null,fullTitle:"Graves' Disease",slug:"graves-disease",publishedDate:"December 1st 2021",bookSignature:"Robert Gensure",coverURL:"https://cdn.intechopen.com/books/images_new/10312.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"16515",title:"Dr.",name:"Robert",middleName:null,surname:"Gensure",slug:"robert-gensure",fullName:"Robert Gensure"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11729",leadTitle:null,title:"Circumcision - Advances and New Perspectives",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tMale circumcision is a procedure that has been practiced since the dawn of human culture more than six thousand years ago. It is performed for both medical and non-medical reasons. Despite being a simple procedure, it may lead to a myriad of minor and even crippling complications, if not done properly, such as iatrogenic injury of the glans or the urethra. Several techniques have been used to perform circumcision including the classic open technique, clamp technique, and laser /electrocautery technique with various safety outcomes. Overtime time, there has been an ongoing debate over the pros and cons of cultural circumcision with a significant dichotomy between the opinions of the experts in the field.
\r\n\r\n\tThe main purpose of this book will aim to present a comprehensive overview of the historic background of circumcision in males and the debate over female circumcision. It is intended to be an addition to a description of the different procedural techniques of circumcision highlighting their potential complications.
",isbn:"978-1-80355-907-0",printIsbn:"978-1-80355-906-3",pdfIsbn:"978-1-80355-908-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"d4761c03b5694edec9f7fc48092549ce",bookSignature:"Dr. Ahmad Zaghal and Dr. Ali El Safadi",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11729.jpg",keywords:"History Of Circumcision, Male Circumcision, Female Circumcision, Indications, Contraindications, Peri-Procedural Preparation, Analgesia, Clamp, Meatal Stenosis, Iatrogenic Injury, Adhesions, Buried Penis",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 25th 2022",dateEndSecondStepPublish:"April 29th 2022",dateEndThirdStepPublish:"June 28th 2022",dateEndFourthStepPublish:"September 16th 2022",dateEndFifthStepPublish:"November 15th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Pediatric surgeon and clinical educator, member of Royal College of Surgeons of England, European Pediatric Surgeon’s Association, British Association of Pediatric Endoscopic Surgeons, American College of Surgeons, International Society for Pediatric Wound Care.",coeditorOneBiosketch:"Obstetrics and Gynecology trainee and clinical researcher.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"240621",title:"Dr.",name:"Ahmad",middleName:null,surname:"Zaghal",slug:"ahmad-zaghal",fullName:"Ahmad Zaghal",profilePictureURL:"https://mts.intechopen.com/storage/users/240621/images/system/240621.jpg",biography:"Ahmad Zaghal, MD, MSc (Clin Ed), FACS, FEBPS, FHEA, graduated from the general surgery-residency program at The American University of Beirut-Medical Center (AUBMC), Lebanon, in 2012. He then completed a two-year fellowship in Pediatric Surgery at the University of Iowa-Hospitals and Clinics, USA. Then he joined Chelsea and Westminster Hospital, UK, for another year of fellowship in pediatric surgery. Dr. Zaghal is board certified by the European Board of Pediatric Surgery.\nDr. Zaghal has been a pediatric surgeon and assistant professor of surgery at AUBMC since 2017. He has special interests in minimally invasive and neonatal surgery, and medical education. He is a fellow of the Higher Education Academy. Dr. Zaghal has published several articles in peer-reviewed journals and authored several chapters in general and pediatric surgery.",institutionString:"American University of Beirut",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"American University of Beirut",institutionURL:null,country:{name:"Lebanon"}}}],coeditorOne:{id:"450673",title:"Dr.",name:"Ali",middleName:null,surname:"El Safadi",slug:"ali-el-safadi",fullName:"Ali El Safadi",profilePictureURL:"https://intech-files.s3.amazonaws.com/a043Y00000rTNkyQAG/Co1_Profile_Picture__c%202021-12-20%2012%3A56%3A08.218",biography:null,institutionString:"American University of Beirut Medical Center",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"American University of Beirut Medical Center",institutionURL:null,country:{name:"Lebanon"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"184402",firstName:"Romina",lastName:"Rovan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/184402/images/4747_n.jpg",email:"romina.r@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"62647",title:"Indomethacin from Anti-Inflammatory to Anticancer Agent",doi:"10.5772/intechopen.79677",slug:"indomethacin-from-anti-inflammatory-to-anticancer-agent",body:'\nIndomethacin is indole-3-acetic acid derivative, classified as nonsteriodal anti-inflammatory drug (NSAID). The drug is primarily used for the treatment of painful inflammatory conditions that involves gout and osteoarthritis [1]. The mechanistic role of indomethacin in inhibition of pain has been verified by being nonselective inhibitor to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isozymes [2]. The enzymatic activity of COX involves bis-oxygenation of arachidonic acid to (prostaglandin G2) PGG2, which then reduced to PGH2 in a peroxidase reaction by the same protein [3]. COX-1 is constitutively expressed in most tissues, to which the production of prostaglandins is attributed to; and COX-2, which is induced by cytokines, mitogens and endotoxins in inflammatory cells, is implicated to the elevated levels of prostaglandins during the inflammation. Prostaglandins are hormone-like mediators involved in the induction of pain, fever and inflammation [2]. The inhibition of indomethacin to the two COX isozymes with minimal selectivity to COX-2 made the drug have serious complications such as gastric ulcers and renal toxicity upon long-term oral administration [4, 5].\n
Indomethacin and the other NSAIDs were found to have significant anticancer activity against wide variety of cancer cell types,
Interestingly, to mention that the mechanism to which the anticancer activity of NSAIDs including indomethacin attributed is the reduction of PGE2; a type of prostaglandins generated from the bis-oxygenation of arachidonic acid by COX-2. PGE2 contributes to the cell proliferation, cell cycle proliferation and cell cycle progression through various cell signaling mechanisms leads to induction of oncogenic genes and eventually overexpression of proliferative proteins [18, 19, 20, 21, 22]. Recently, extensive studies on various cancer cell types including colorectal carcinoma (CRC) justified the efficacy of indomethacin to reduce the levels of antiapoptotic proteins and progressive cell proliferation represented by tumor size by COX-independent mechanisms [23, 24, 25, 26].
\nAfter emerge and marketing of celecoxib; selective COX-2 inhibitor in December 1998, rofocoxib was released in 1999 worldwide then lumiracoxib and etoricoxib (Figure 1) that are marketed in Europe. Those inhibitors are still marketed for the treatment of inflammatory disorders except for rofecoxib and lumiracoxib (the only carboxylic coxib) that were withdrawn due to observation of cardiovascular complications from the recommended daily dose with rofecoxib [27] and observation of liver failure with lumiracoxib [28]. Selective COX-2 inhibitors were launched to treat the individuals who cannot tolerate severe gastrointestinal responses of NSAIDs. A few years later, extensive preclinical and clinical data generated to report the role of COX-2 in tumor growth and/or metastasis [29]. Studies on experimental animals showed that selective COX-2 inhibitors including celecoxib block the formation, growth and metastases of multiple tumor types [30]. Consistently, celecoxib demonstrated dramatic chemopreventive efficacy against colon polyps and reduced the incidence of recurrent adenomas of any type by 45% and of high risk lesions by 66% over a 400 mg dose twice daily for 3 years [31, 32]. One of the complications that should be tackled in the near future for selective COX-2 inhibitors celecoxib in specific is the cardiovascular complications that comes after administration of 400 mg twice daily to be the same as the dose recommended for chemopreventive effect to control the recurrence of CRC [32, 33]. The magnitude of cardiovascular complications of celecoxib limits its use for colon cancer prevention since the development of colon cancer is a slow process, so, the patients with polyps would need to take celecoxib for a long period of time to achieve the target protective effect. Accordingly, a question should be admitted, and should have an evidenced answer: Does the cardiovascular problems of selective COX-2 inhibitors class of anti-inflammatory agent come out of pharmacological class effect or chemical class effect? To my knowledge, we cannot confirm that it is pharmacological class effect and not chemical class effect because the chemical structure of COX-2 inhibitors that share the CVS side effects are Y-shaped diaryl-heterocycle sulfonamide/methylsulfonyl. Thus, it is required to develop new chemical class of selective COX-2 inhibitors help us be provided with verified answer to such important question. The answer of the question would raise the concern to the main reason(s) of CVS complications to tackle and eventually modify the strategy toward generation of selective COX-2 inhibitors with chemopreventive benefits against CRC and other cancer cell types.
\nDiarylsulfonamide/methylsulfone selective COX-2 inhibitors.
Based on the above findings indomethacin, as nonselective COX-inhibitor could be considered strategic lead compound that worth it studying and developing to line it among the chemotherapeutic agents used against cancer to be either prophylactic or therapeutic treatment and/or even adjuvant therapy upon combination with other anticancer agents to synergize the chemotherapeutic effect [25]. The subjected insight in this book chapter regarding indomethacin could be easily justified on scientific bases: (1) indomethacin is the most NSAID that is intensively studied as chemopreventive and chemotherapeutic agent against multiple cancer cell types among the other drugs of the same class to show observable results. (2) Indomethacin as a different chemical class when compared to selective COX-2 inhibitors, developing indomethacin-based selective COX-2 inhibitor to excel celecoxib would benefit in asserting whether the cardiovascular system (CVS) problems are originated from chemical class effect. In case, the reason of the cardiovascular system (CVS) complications is attributed to the chemical class effect and indomethacin-based developed structures are devoid of the complications, the patients would be largely benefited from such class of compounds, and it would be chemopreventive agents used for long time without developing cardiovascular system (CVS) complications. (3) Kinetic profile of indomethacin inhibition to COX-2 shows recovery after long time of tight binding to the enzyme [34], and on the other hand, selective COX-2 inhibitors’ kinetic profile shows no recovery even after long time of tight binding [35]. This obvious difference between indomethacin and selective COX-2 inhibitors in performing the functionally irreversible inhibition effect to COX-2 has to lead us highlighting indomethacin as promising base to build upon it the developed structures in a way to generate selective COX-2 inhibitors with minimized serious side effects observed with the diaryl heterocycle sulfonamide/methylsulfone class of compounds.
\nThe book chapter covers progressively and in detail some critical topics served in concluding future trends in regard to developing indomethacin to be effective chemopreventive and treatment of various cancer cell types without induction of severe cardiovascular system (CVS) complications:
PGE2 implicated in promoting cell proliferation of human esophageal squamous cell carcinoma. The study started with observation of expression and upregulation of c-Myc, an oncogenic transcription factor, and then a link was expected to exist between PGE2 and c-Myc but requires a reliable elucidation. Deeper studies revealed that PGE2 substantially increased the proliferation of cultured esophageal squamous cell carcinoma cells and increased mRNA and protein expression of c-Myc. Moreover, knockdown of c-Myc by RNA interference significantly attenuated PGE2-induced cell proliferation. Furthermore, a mechanistic study described that stability and nuclear accumulation of c-Myc oncogenic protein is attributed PGE2 via phosphorylation on serine 62 that induced by extracellular signal regulated kinase (ERK)-dependent manner and this was confirmed when PGE2 activation of ERK was fully abolished by protein kinase C (PKC) inhibitors. Consistently, PGE2 receptor (EP2) agonist resulted in the same effect on expression of c-Myc as PGE2 and knockdown of EP2 receptor by EP2 small interfering RNA (siRNA) delayed PGE2-induced c-Myc expression to verify the association of PGE2 to c-Myc protein expression in esophageal squamous cancer cell proliferation [18].
\nIt was reported for celecoxib to be effective after Helicobacter Pylori eradication therapy in improving gastric precancerous lesions and stops progression into cancer. The therapeutic effect of celecoxib is explained in the study by measuring the expression and activity of COX-2 for patients with gastric precancerous lesions received celecoxib up to 3 months to be compared with those received placebo for the same period of time. The measurements were determined by immunostaining and PGE2 assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular disease (MVD) assay using CD31 staining. The results showed that there was a significant elevation in COX-2 protein expression in gastric precancerous lesions when compared with that resulted from chronic gastritis with consequent increase in cell proliferation and angiogenesis. Patients who were treated with celecoxib showed significant improvement in gastric precancerous lesions (sites of dysplasia) with 84.6% regressed dysplasia, while those treated with placebo showed 60% suggesting that celecoxib was effective on the regression of dysplasia. On the other hand, celecoxib effectively suppressed cell proliferation, induced cell apoptosis and inhibited angiogenesis exhibited by decreased MVD. Interestingly, COX-2 inhibition was accompanied by up-regulation of PPARγ expression that is protective protein with reported antineoplastic effects [36].
\nOverexpression of COX-2 frequently occurred in head and neck squamous cell carcinoma (HNSCC). COX-2 promotes the release of pro-inflammatory mediator PGE2 which binds to cell surface G-protein coupled receptors EP1–4 to exert its pharmacological effects. Upon studying the biochemical functions of PGE2 and its cell receptors in HNSCC cellular proliferation, it was found that COX-2 and cell receptors EP1, EP2 and EP3 were constitutively expressed in tumoral lesions of HNSCC. An important finding was declared in the study states that small concentration of selective COX-2 inhibitors succeed to suppress PGE2 without inhibition of cell proliferation. However, exogenous addition of EP3-specific agonists with PGE2 induces DNA synthesis in all HNSCC cell lines. Thus, it could be suggested that EP3 receptor subtype of PGE2 should be regarded for future strategies targeting HNSCC prevention [19].
\nAnother study defined a critical mechanism to justify the role of PGE2 in promoting CRC cell division in which prometastatic adaptor protein human enhancer filamentation 1 (HEF1) links between PGE2 and cell cycle machinery in CRC cells. PGE2 induces expression of HEF1 mRNA and protein in CRC. Knockdown of HEF1 suppresses PGE2-induced cell proliferation and cell cycle progression. CRC cells were examined and found that there is 50% elevated levels of HEF1 when compared to normal tissues. Further, HEF1 promotes cell cycle progression of colorectal carcinogenesis via interaction with and activation of cell cycle kinase Aurora A to report that PGE2 is inducer to crucial downstream mediator, HEF1 in colorectal carcinogenesis [20].
\nSmall noncoding RNA, microRNAs (miRNAs) have a key role in stopping the translation and accelerate the degradation of mRNA that regulates the cellular growth and survival through gene suppression. miRNA has a significant contribution in controlling disease progression in pancreatic cancer cells (PaCa). Elevated levels of COX-2 were observed with PGE2 and decrease in miRNA increased the cancer growth and metastases of PaCa. Restoration of miRNA-143 (miR-143) in human PaCa cells reduced COX-2 and inhibited cell proliferation. Mitogen activated kinase (MAPC) was correlated to not detecting miR-143 in some pancreatic cancer cell subtypes to justify the implication of MAPC activation in regulating miR-143 beside COX-2 and PGE2 [21].
\nα7 Nicotinic acetylcholine receptor (nAChR) protein is significantly biosynthesized via cholinergic signaling in nonsmall cell lung cancer (NSCLC) beside COX-2-driven PGE2. The mechanism by which PGE2 promoted NSCLC cell proliferation over α-7 nAChR induction showed the positive effect of PGE2 on α7 nAChR expression, promotor activity and cell signaling pathways. The association of the two stimulatory factors to cell growth of NSCLC cells was confirmed upon attenuation of PGE2-induced cell proliferation via α7 nAChR siRNA or acetylcholine transferase. Moreover, PGE2 induced α7 nAChR production was blocked by EP4 receptor antagonist and EP4 siRNA. Furthermore, it was recorded that blocking c-Jun, critical transcription factor, activated by c-Jun N-terminal kinase (JNK), phosphoinositol 3-kinase (PI3K) and protein kinase A (PKA), led to abolishing the PGE2-induced α7 nAChR production and consequent cell growth. It is worthy to mention that activation of JNK, PI3K and PKA resulted from acting of PGE2 on EP4 receptor subtype [22].
\nChemopreventive effects of indomethacin was observed for 4-hydroxybutyl(butyl)nitrosamine(OH-BBN)-induced urinary bladder cancers in mice. The study came over conducting three experiments in which the indomethacin was continually administered prior to week 1 or following week 13 OH-BBN dosing for 32 weeks, 1 week after intake of OH-BBN at week 13 for 12 weeks and 30 weeks, and 1 week after intake of OH-BBN at week 13 for 61 weeks, respectively. The chemopreventive effect of indomethacin was observably impressive to show development of palpable bladder masses 3% of animals in case of experiment 1, 77% decrease in palpable masses and 82% decrease in palpable and microscopic masses in case of experiment 2, 26% developed palpable mass under treatment of indomethacin and 66% in control group in case of experiment 3 [26].
\nApoptosis is a programmed cell death induced intrinsically by mitochondrial-mediated or extrinsically by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated signals [37]. Caspase activation is generally accompanied by apoptosis that is dependent on mitochondrial mediated or classical extrinsic TRAIL- or death receptor (DR)-mediated signaling [25]. Tse et al. reported the capability of indomethacin to make tumor cells responsive to TRAIL-mediated apoptosis signals through upregulation of TRAIL receptor (DR 5) and down-modulation of survivin, antiapoptic protein [38]. The report provided convincing mechanism to the indomethacin-induced process to overcome TRAIL-resistant melanomas. It is well known that indomethacin enhances mitochondrial oxidative stress and the production of reactive oxygen species (ROS) that modulate mitochondrial-mediated signaling [39]. ROS induces the transcription factor, C/enhancer-binding homologous protein that leads to upregulation of DR 5 on tumor cells. Moreover, ROS has a role in down-modulation of surviving via inhibition of transcription of the known regulator, NF-kB [37]. The report suggests that indomethacin could successfully sensitize TRAIL-resistant melanoma cells.
\nThe ability of indomethacin to work against HCT116 human CRC cells does not express COX was reported using proteomic approach to identify the mechanism by which indomethacin inhibit the CRC growth. The total proteins from indomethacin-treated and untreated cancer cells were separated by immobilized pH gradient-based two-dimensional gel electrophoresis. The different proteins produced throughout the test were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time of flight mass spectrometry. The results revealed that indomethacin induced HCT116 apoptosis and inhibited cell growth by downregulation Wnt1-inducible signaling pathway protein 1, Bcl-2-related protein A1 and mitogen-activated protein kinase [24].
\nc-AMP activates PKA in and c-AMP-response element binding (CREB) protein in melanogenesis. CREB plays an important role in binding to the promotor of the microphthalmia-associated transcription factor (Mitf) gene and consequently activates Mitf gene transcription [40, 41]. Thus, Mitf has a crucial role in transcription of melanogenic genes and activates melanogenic gene transcription of tyrosinase as well. Indomethacin was studied to investigate the effect on melanogenesis in B16F1 melanoma cells. The study resulted in indomethacin inhibited α-melanocyte stimulating hormone that enhances melanin synthesis in melanoma cells., suppressed tyrosinase and Mitf protein levels, reduced tyrosinase promoter activity, lowered mRNA of melanogenic genes, including Mitf gene [23].
\nAMP-protein kinase (AMPK) is a key factor of master regulation of cellular energy homeostasis [42]. When AMPK is activated, it induces block of cell cycle and apoptotic cell death in different types of cancer cells including gliomas, the primary tumors of central nervous system [43, 44, 45, 46, 47]. The apoptotic death and inhibition of growth of cancer cell actions of AMPK are mediated by one of the signaling pathway in which mammalian target of rapamycin (mTOR) is inhibited. It is worthy to note that mTOR is a catalytic core for formation of two definite complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2) and both are sensitive targets to rapamycin, allosteric inhibitor of the complexes [48]. mTORC1 has a supporting role in protein synthesis and cell proliferation. mTOR performs its biological functions by phosphorylating ribosomal p70S6 kinase and translational repressor 4E-BP1 [48]. AMPK phosphorylates raptor and/or tuberous sclerosis complex-mediated inhibition of mTOR stimulator Ras homolog enriched in brain (RHEB) [49]. Beside the role of mTORC1 in cell proliferation, it causes major and observable negative regulation to intracellular degradation of unnecessary and dysfunctional cellular components through lysosomal machinery which is a kind of cytotoxic mechanism [50]. Indomethacin was reported as growth inhibitor to CRC cells by mTOR inhibition [51]. For the glioma cells U251, indomethacin showed superior
According to the literature scan had been done on indomethacin as nonselective COX-inhibitor and antiproliferative agent, it could be observed that indomethacin is the most NSAID that attracted the interest of researchers to study, investigate, identify more about the definite mechanisms and cellular signaling pathways involved in the antiproliferative and apoptotic effects of indomethacin. This might be attributed to two apparent points: one is the observable inhibition of cell growth, reduction of tumor size and implication in the programmed cell death of multiple tumor cell types including glioma and glioblastomas that require lipophilicity for cell penetration. The second is that indomethacin exhibited its anticancer activity against wide variety of cancer cell types by COX-2/PGE2-dependent and -independent mechanisms. This adds great advantage to indomethacin over the other nonselective COX-inhibitors because in that way, indomethacin has dual actions by which it could exert its cytotoxic activity effectively.
\nRegarding the selective COX-2 inhibitors, the prophylactic actions of celecoxib against recurrence of colon polyps is defined by researchers as dramatic to indicate the capability of celecoxib and other COX-2 inhibitors to block the cancer cell growth and metastases as well. One serious complication that is developed upon long-term therapy of celecoxib that limits its use as chemopreventive therapy for CRC is the cardiovascular toxicity that results from critical reduction in PGE2 and prostacyclin (PGI2) production. Those types of prostaglandins are COX2-dependent product responsible for regulating vascular tone and atherosclerosis [53]. The problem is absolutely the same as all the selective COX-2 inhibitors since they share the same pharmacological action in which production of prostaglandins is significantly diminished.
\nSome differential points related to the kinetic profile of both indomethacin [34] and selective COX-2 inhibitors [35] were worth it stopping at to help us draw a future plan to develop indomethacin’s chemical structure in a way to enhance COX-2 inhibition activity like selective COX-2 inhibitors and be devoid of cardiovascular complications as well. Nonselective inhibitors including indomethacin perform its inhibition action against the enzyme through 2-step inhibition mechanism involving slow and time-dependent step due to tight reversible binding to the enzyme to be considered as functionally irreversible. But selective COX-2 inhibitors inhibit the enzyme through 3-step inhibition mechanism involving time-dependent step that represents the tightly bound complex of inhibited enzyme. The observation that should be highlighted for both types of COX-inhibitors while monitoring the kinetic model of inhibition mechanism is that indomethacin carboxylic acid is not essential for the tight binding and time-dependent step of enzyme inhibition because the esterified counterpart did not abolish this step or even reduce the tightness of binding to human COX-2 and the formation of the complex maintained functionally irreversible [54, 55]. Further, indomethacin recovered intact after prolonged time of incubation with the enzyme, this suggests that enzyme inhibition came over conformational change not covalent bond formation [34]. On the other hand, DuP 697, selective COX-2 inhibitor showed the same time-dependent step that was responsible for drug’s selective inhibition of human COX-2 but impressively the inhibitor did not show successful recovery even upon dialysis but the inhibitor is freed to inhibit another enzyme under the effect of denaturation to confirm that the tight binding of inhibitor to the enzyme was not based on formation of covalent bond [35].\n
The detrimental differences in regard to the kinetic profile of indomethacin, nonselective COX-inhibitor and DuP 697, selective COX-2 inhibitor for inhibition of COX-2 raised my concern with that emerge of developed selective COX-2 inhibitors based on indomethacin would definitely help us answer two important questions:
Several attempts for generation of indomethacin-based analogs of selective COX-2 inhibition activity [58, 59, 60], but the publication that I had to put it in focus in this regard is that described the design and synthesis of indomethacin-based analogs of potentially selective COX-2 inhibition activity and observed diminishing to PGE2 [61]. The successful generation of developed indomethacin structures with selective COX-2 inhibition activity was iteratively reported in the literature but picking this publication to comment on among the others was based on the obvious selectivity index of the generated analogs that excelled celecoxib, dramatic lowering to plasma levels of PGE2 when compared to indomethacin, the innovative perspective upon which the design and modification of the analogs are designed, and above all of this the biological profiling through multiple
The new tetrahydrocarbazole selective COX-2 inhibitors
Biological data of the new indomethacin-based selective COX-2 inhibitors 1 and 2 in comparison with indomethacin and celecoxib.
Schematic representation of SC-558 (COX-2 selective inhibitor) binding to COX-2 (a) and indomethacin (nonselective inhibitor) (b).
Generation of indomethacin-based analogs to indomethacin aiming at enhancing the selective COX-2 inhibition would definitely help us answer an important question concerning the real reason of cardiovascular toxicity of selective COX-2 inhibitors, whether it is pharmacological class effect or chemical class effect. Moreover, enhancing the selectivity of indomethacin against COX-2 among the other NSAIDs providing a candidate privileged with potential anti-inflammatory activity devoid of gastrointestinal side effects and what is more important is obtaining newly developed structure carries effective antiproliferative and apoptotic activity standing for the dual actions reported for indomethacin as a lead compound based on that it performs its anticancer activity by both COX-2-dependent and COX-2-independent mechanisms. Further, the CVS toxicity is expected to be minimized upon enhancing the selective COX-2 inhibition of indomethacin due to observation that there might be a difference in the kinetic mode of enzyme inhibition between diaryl heterocycle sulfonamide/methylsulfone chemical class of selective COX-2 inhibitors and the new indomethacin-based chemical class of compounds that may permit successful recovery of the new inhibitors from the enzyme after long incubation period.
\nNSAID | nonsteroidal anti-inflammatory drug |
COX | cyclooxygenase |
PG | prostaglandin |
CRC | colorectal carcinoma |
CVS | cardiovascular |
ERK | extracellular signal regulated kinase |
PKC | protein kinase C |
siRNA | small interfering RNA |
MVD | microvascular d |
HNSCC | head and neck small cell carcinoma |
HEF1 | human enhancer filamentation 1 |
miRNA | microRNA |
MAPC | mitogen activated kinase |
NSCLC | nonsmall cell lung cancer |
JNK | c-Jun N-terminal kinase |
PI3K | phosphoinositol 3-kinase |
PKA | protein kinase A |
OH-BBN | 4-hydroxybutyl(butyl)nitrosamine |
TRAIL | tumor necrosis factor-related apoptosis-inducing ligand |
DR | death receptor |
ROS | reactive oxygen species |
PMF | protein mass fingerprint |
CREB | c-AMP-response element binding |
AMPK | adenosine monophosphate kinase |
mTOR | mammalian target of rapamycin |
RHEB | Ras homolog enriched in brain |
Abrasive cutting is widely used in industry due to its high production rate (machining is performed at a speed of 100–200 mm2/s) and low labor costs. It is characterized by high temperatures (above 1000°C) in the cutting zone, intensive wear and deterioration of the abrasive tool cutting ability, spark generation, increased emissions of environmentally harmful gases, high noise level, risk of accidents, changes in the microstructure of surface materials and occurrence of thermal flaws [1, 2, 3, 4, 5, 6, 7]. Those disadvantages are related to the high cutting speed (above 50 m/s), constant changes in cutting conditions within a cut-off cycle, and unfavorable geometry of abrasive grains (negative rake angles).
Almost all mechanical work (over 97%) converts into thermal energy and only a small part of it transforms into hidden energy to change the crystal lattice of the material being machined [8, 9].
As a result of the conversion of the mechanical energy used in the cutting process into thermal energy, various heat sources emerge and the process of generating that heat depends on cutting conditions.
As far as every physical phenomenon has two sides—quantitative and qualitative, then, as a rule, the control of the energy transfer in a specific physical phenomenon involves the measurement of two quantities. When controlling heat exchange processes, the two quantities to be measured are temperature and thermal flux. Measuring the thermal parameters of thermal non-stationary processes, in particular, a rapidly changing thermal flux remains relevant today. Among the techniques for measuring unstable thermal fluxes, those using infrared cameras are preferred [10, 11, 12]. Infrared thermography provides remote and wireless real-time measurements of temperature fields of high-speed moving objects. However, to obtain accurate measurements, all emerging noises and interferences need to be compensated or minimized, which is а kind of a “payoff” for the universality of the thermographic thermal control.
By changing the abrasive cutting conditions, which directly define the thickness of the layer of material being cut, and, as a result, the temperatures of the tool, chip, workpiece, and cut piece, the thermal fluxes are controlled and conditions for increasing the tool life, the intensity of the cutting process and the quality of the machined surfaces are provided. Therefore, to improve the effectiveness and applicability of abrasive cutting, it is necessary to study and model the parameters of the process and to optimize the conditions for its implementation. This allows us to apply thermographic monitoring for preventive detection of unexpected changes in the parameters of the elastic abrasive cutting process and for ensuring a high-quality process.
To study the thermal phenomena in elastic abrasive cutting, an innovative approach has been used. It involves a wireless thermal control provided by infrared thermography and the application of the methodology of planned experiments and multi-objective optimization. An original thermographic procedure for increasing the precision of the thermal control during abrasive cutting is offered.
The manufacture of workpieces by cutting is implemented on various machines and installations (automatic lathes, band cutting machines, mechanical hacksaws, band saws circular saws, abrasive cut-off machines, presses, electric spark, and electrochemical installations) depending on the dimensions, profile, type and physico-mechanical properties of the input material and the admissible deviation from nominal dimensions. When comparing cutting methods by technological criteria, the most important criteria are cutting intensity (production rate), tool life, and material loss in the form of chips related to the cut width. Choosing an optimal variant for workpiece cutting is a technical and economic task, which has a considerable impact on the cost of the machine-building production.
Abrasive cutting is a universal method that is applied to manufacturing workpieces of metal and non-metal materials of different hardness by means of high-speed reinforced abrasive (cut-off) wheels of a diameter
Reinforced cut-off wheels whose grain size is in compliance with ISO 8486—grain numbers from 24 (coarse) to 60 (fine); medium-hard (
Abrasive cutting is a complex and varied process performed under different kinematic schema (Figure 1) where the cut-off wheel performs the main rotary motion (at a rotational frequency
Schemas of abrasive cutting.
The oscillatory motion facilitates the cutting process and helps to reduce the cost of the abrasive wheels. However, some shocks occur at both ends of the oscillatory motion, which leads to overloading the cut-off wheel, occurrence of vibrations, and an increase in wear. The implementation of such a motion makes the machine complex and costly. Those disadvantages are avoided when using the schema including a rotary motion of the workpiece (Figure 1c). If we compare abrasive cutting schemas, it can be seen that when performing a cut-off cycle (cutting one workpiece), the cut-off wheel working stroke upon cutting a rotating workpiece (Figure 1c) is approximately twice as short as that for the schemas in Figure 1a and b. It results in reducing the cut-off time and the friction forces between the lateral surfaces of the cut-off wheel and workpiece thus, on one hand, decreasing the temperature in the cutting zone and cut-off wheel wear and, on the other hand, increasing process production rate. When cutting a rotating workpiece, the lower cut-off wheel wear and the higher production rate is also due to the shorter length
The cut-off wheel can be fed into the workpiece at a constant speed of radial feed (
The kinematic schemas of rigid abrasive cutting are similar to those in external cylindrical grinding, where dependencies for defining the tool-workpiece contact area, contact arc length, and thickness of layer being cut, pointed in [14, 18, 19, 20], are required. The principal disadvantage of this method is the change in the power and heat loads of the cut-off wheel within one cut-off cycle, which is related to the change in the instantaneous cross-sectional area of the layer is cut. This results from the fact that with the cut-off wheel feed from the periphery to the center of the workpiece being cut the contact arc length between the cut-off wheel and the piece changes as the instantaneous thickness of the layer being cut
Within one cycle of elastic abrasive cutting, the length of the contact arc
The increase of the compression force
The increase in the workpiece rotational frequency
As the cut-off wheel diameter
The analysis has been carried out shows that elastic abrasive cutting is a sophisticated multi-parameter and multi-factor subject of study, modeling, and optimization [24]. It is characterized by a number of target parameters—economic (productivity and cost), dynamic (cutting forces and power) and technological (cut-off wheel wear and tool life, cutting temperature, noise, roughness and precision of machined surfaces, physico-mechanical properties of the surface layer—structure, microhardness, surface residual stresses, flaws, etc.). Each of the above parameters has a specific meaning in relation to abrasive cutting yet is insufficient for its optimum control.
The parameters of elastic abrasive cutting are determined by numerous control factors—physico-mechanical properties of the materials being machined, methods and components of the cutting mode, cut-off wheel type and characteristics, type and way of supplying cooling fluids, etc.
In the course of abrasive cutting, a number of interrelated, yet of a different type, nature, and intensity, phenomena occur and various materials, cut-off wheels, and cutting modes are used. Each abrasive cutting process is unique and could be studied from different perspectives: technological, energetic, informational, organizational, etc. When it is investigated, new experimental data and models are obtained, which differ from those of the preceding processes. Therefore, its investigation, modeling, analyzing, control, and optimization are always specific.
The mechanical work done in cutting involves deformation (elastic and plastic) of the material being machined, action of friction forces on the face and flank of cutting abrasive grains, and formation of new surfaces (dispersion). The amount of heat generated in cutting per unit of time, expressed by the work done in cutting and the mechanical equivalent of heat (
where:
Intensive thermal fluxes flow through the tool, chip, and material being machined in high-speed abrasive cutting. The large amount of heat generated in the course of abrasive cutting is transferred to the workpiece (
A wide range of changes in the thermal flux components depending on the selected schema for process implementation (rigid or elastic abrasive cutting), the characteristic of the cut-off wheel, the physico-mechanical properties of the material being machined and the cutting mode has been established.
Actually, the whole action of the friction forces in the contact zone below the neutral line
Schema of chip formation in abrasive cutting.
During the initial contact between the abrasive grain and the workpiece, taking into account the comma-shaped cross-section of the layer being cut when
When the values of the layer being cut are
The part of heat transferred to the workpiece is reduced when increasing the cutting speed because of the change in the ratio between the cutting speed and the heat dissipation rate in the deformation zone [14, 17, 19]. The dissipation rate of generated heat depends on the gradient of the temperatures along the shear surface and the heat conductivity of the material being machined. When the cutting speed, i.e. the speed at which the abrasive grain crosses the thermal flux, is low, the heat from the shear surface is transferred unobstructed to the workpiece. As the cutting speed increases, the cutting abrasive grain crosses the thermal flux faster and faster. As a result, a smaller amount of heat is transferred to the workpiece and a larger amount of heat remains in the chip:
where
Since a large part of heat (almost all the heat generated by plastic deformation and part of the heat generated by friction) is generated in the chip, the largest part of process heat remains there. Heat in the abrasive grain occurs externally as a result of friction and heat transfer from the hot chip to the colder abrasive grain, from plastic deformation, from the shear of the material under the neutral line, as well as from friction along the grain flank. As a consequence of conduction, the heat generated on the surface AB (Figure 2) is transferred to the abrasive grain and workpiece. The better the heat transfer from the surfaces being heated, the lower the temperature of those surfaces, i.e. the properties of heat conductivity and heat resistance influence the performance of cut-off wheels and the quality of machined surfaces.
The temperature of the cut-off wheel work surfaces (above 100°C) depends on the thermal flux density
The cutting process in abrasive cutting is accompanied by melting of chips and plenty of sparking, which result from a large amount of heat generated in the cutting zone by friction forces, deformation of the material being machined, and reaction during burning. During burning every material has a specific point at which it ignites. When reaching the ignition temperature under the influence of oxygen, the physically and chemically clean surfaces of the steel workpieces being machined are oxidized to form iron oxide and slag. During oxidation, a considerable amount of heat is released, which provides additional heating of the very small volumes of metal of the chips removed by the abrasive grains up to the melting temperature. The presence of carbon in the material being machined increases burning and the temperature in the cutting zone, which is the reason for the different colors of the formed sparks in abrasive machining. Under the influence of the high speed of the abrasive cut-off wheel grains, the slag and iron oxide been formed are removed as glowing sparks [17]. The oxidation of the chip and the material being machined is useful since the oxide crust is fragile and facilitates chip removal. In accordance with the foregoing, the melting of the chip can be viewed as a positive factor because after melting the chip decreases its dimensions, which contributes to its easier removal by the cut-off wheel and to avoiding the filling of the tool pores with chips.
The burning of materials in abrasive cutting does not allow us to directly measure the temperature of the removed chip since it ignites when it forms or immediately after that. The brightness and type of sparks formed during abrasive machining (a product of burning) are defined solely by the content of the chemical elements in the material being machined. The density and length of the spark flow depend on the components of the cutting mode.
The increase of the heat entering the cut-off wheel intensifies tool wear and decreases tool reliability and cutting intensity as a result of a decrease in the relative pressure of the abrasive grains on the surface being machined (because of the softening of the cut-off wheel bond). Heating up the workpiece in the cutting zone leads to changes in the microstructure of the surface material and the occurrence of thermal flaws. Structural changes in the cross-section of the cut, which require further machining, also occur as a result of smearing and chipping parts of the cut-off wheel, as well as of friction between its lateral surfaces and workpiece face [6, 7]. All the above mentioned demonstrates the decisive role of temperature in abrasive cutting regarding cut-off wheel performance and quality of machined surfaces. It also shows that the heat released in the course of abrasive cutting is an important informative factor for optimizing the operating conditions in abrasive cutting and enhancing the effectiveness of the process and the quality of machined surfaces. Therefore, it needs to be studied, modeled, and optimized. The investigation and measurement of temperature distribution in abrasive cutting play a key role in machine building.
A great number of studies [4, 7, 15, 21, 22, 28] show that by controlling the thermal fluxes in the cutting zone, possibilities for improving the cut-off thermal mode are provided thus ensuring longer tool life, higher intensity of the cutting process and higher quality of machined surfaces. This could be achieved not only by changing abrasive cutting conditions (cutting schema and parameters of cutting mode), which directly determine the thickness of the layer being cut, and respectively the temperatures of the tool, chip, workpiece, and cut piece, but also by choosing the cut-off wheel characteristic.
Depending on the specific nature of cutting processes, various methods for investigating temperature are applied [27]:
Analytical and numerical methods (heat source method; finite difference method; finite element method)—They are based on the heat balance equation and the differential equation of heat conduction [27]:
where:
Experimental methods—They are used to measure the average and local temperatures, determine the zone of temperature distribution, and to visualize the temperature field. According to the way of measurement they are as follows:
Contact methods—Indirect (calorimetric technique, microstructural analysis technique, method of chip coloring, thermal pain technique, and electrical modeling) and direct—thermocouple technique (artificial, semi-artificial, natural, and running). With those methods, the energy exchange between the environment and thermometric substance is based on heat conduction [29].
Wireless measurement methods—They are based on the laws of thermal radiation of bodies. The wireless temperature measurement devices used in practice are as follows: optical pyrometers, spectral ratio pyrometers, radiation pyrometers, infrared thermometers, thermal imaging cameras [29, 30]. Choosing a proper device depends on a number of factors—temperature range, material, object dimensions, distance, ambient temperature. It should also be taken into account that the devices record the total energy in their range of vision. When measuring, they also include additional energy sources, including reflected energy, if they are in the range of vision.
Measuring temperature in abrasive cutting is difficult because of the small dimensions of the zone being heated (only tenths of mm2), high temperatures (hundreds of degrees Celsius), high-temperature gradient (more than 200оС/mm2), high mechanical load, and high heating speed. This predetermines the preferential use of analytical and numeric methods, as well as wireless methods, for investigating the thermal phenomena in that process.
The thermal phenomena in rigid abrasive cutting are well studied unlike those in elastic abrasive cutting. Numeric, analytical, and finite-element models were developed to define and analyze temperature distribution [3, 13, 18, 20, 31]. Thermal fluxes were investigated under different cutting conditions and strategies for optimizing the parameters of rigid abrasive cutting with regard to decreasing the temperature in the cutting zone were proposed [32, 33, 34, 35, 36, 37, 38, 39, 40, 41]. In addition, a high-accuracy simulation model for forecasting temperature was proposed. It can be used for forecasting and preventing thermal flaws [33].
Analytical models for determining the temperature in elastic abrasive cutting were also proposed. On the basis of the analysis of thermal phenomena, the inability to directly measure chip temperature was justified and a methodology and an analytical dependency for the theoretic definition of chip temperature, reflecting the effect of the cutting speed and the workpiece rotational frequency, were proposed [42]. A model of the chip temperature, proving the decisive influence of the thickness of the layer being cut by one abrasive grain on it, was developed. An approach to the theoretical and experimental definition of the amount of heat released for one cut-off cycle and transferred to the workpiece being machined, as well as of the cut piece temperature, was proposed [43].
By applying the calorimetric technique for measuring temperature and the methodology of the planned experiment, a theoretical and experimental model for the temperature of the cut piece made of С45 steel depending on the cut-off wheel speed and workpiece rotational frequency was built. It was established that cut piece temperature decreases as cutting speed decreases and workpiece rotational frequency increases. This effect is related to the enhanced heat removal resulting from an increase in the thickness of the layer being cut, the cross-section of the chip being cut by one abrasive grain, and time per cut.
The possibilities for wireless temperature measurement and monitoring by applying infrared thermography are studied in [4, 7, 25, 44]. It was found that the cut-off wheel compression force on the workpiece had the greatest effect on the maximum cut-off wheel temperature, respectively on the tool life [4, 7]. It was also found that temperature increased as the workpiece diameter increased. Furthermore, when cutting fixed workpieces, the combination of larger cut-off wheel diameter and a greater compression force results in generating higher temperatures and obtaining lower values of G-ratio. Studies were done with a focus on the possibilities of using infrared thermography as a tool for wireless and non-invasive thermal investigation of the process and tools of elastic abrasive cutting of rotating workpieces [25, 44]. Experimental data from thermographic measurements done by an infrared camera regarding the effect of workpiece rotational frequency, compression workforce, and cut-off wheel diameter when machining various materials on the temperature distribution on workpiece surface, cut-off wheel, and cut piece were presented.
The analysis of the methods and approaches used for investigating and monitoring temperature in abrasive cutting shows the advantages of wireless measurement methods such as infrared thermography (IRT). This method is increasingly recognized and widely used as a reliable and effective tool for thermal wireless non-destructive testing under real conditions of dynamic processes such as abrasive cutting [4, 7, 12, 25, 29, 44]. Its application allows us to enhance the effectiveness of abrasive cutting. However, the use of IRT has some disadvantages.
The availability of metal parts in equipment leads to a number of reflections that impede temperature measurements on the surfaces under study and vary depending on their orientation, temperature, and wavelength. Temperature measurements by using thermography do not provide us with absolute temperature values. To obtain such values, we should use modeling and look for a correlation with the change in surface temperature. IRT measurements are indirect with regard to temperature measurements in the cutting zone. Although the cut-off zone can be observed from the side at a specific position of the camera, the infrared radiation from the cut-off wheel, workpiece, and produced chips affect the results from the temperature measurement of the surface being observed. Therefore, a thorough study of the possibilities for applying infrared thermography in abrasive cutting is required.
There is a qualitative and quantitative non-contact thermographic temperature control. Qualitative control does not require obtaining an accurate surface temperature, but it is sufficient to obtain thermal signatures, which are characteristic models of relative temperature phenomena at different combinations of the abrasive cutting process control factors values. The relative temperature values of the objects in the cutting area to the temperatures of the other equipment objects with similar conditions are used. Quality visual inspection is appropriate for collecting a large number of detailed data and transmitting them for easy interpretation. It is suitable for controlling the efficiency of the process by monitoring the temperatures of the cut-off wheel, workpiece, cut piece, and chip under certain conditions of the abrasive cutting process.
In quantitative thermographic measurement, the ambient temperature is the reference. The observation of the abrasive cutting is established by measuring the absolute temperature of the studied object, under the same environmental conditions. As the reference temperature must be measured, this requires even better knowledge of the variables affecting the radiometric measurement, as well as taking into account the limitations.
The transition from qualitative to quantitative thermographic control is associated with the need to solve four tasks:
Methodical provision of the procedure for determining the surface temperature of the objects participating in the cutting process with the respective metrological analyses;
Obtaining information about the spectral normal emissivity of the object and its surrounding background for the entire spectral range of the optoelectronic system;
Taking into account the influence of the layers covering the surface of the controlled objects, partially transparent to the heat radiation, on the accuracy of determining the surface temperature by non-contact methods;
Measurement of temperatures comparable to the temperature background, taking into account the influence of the background heat radiation on the experimental results.
The aim of the study is first to develop a methodology for monitoring the evolution of surface temperature to identify the process of elastic abrasive cutting by IRT. For this purpose, a modular thermographic measuring system is proposed to monitor the process from different positions.
The illustrated in Figure 3a and b setup is a part of the more complex experimental framework, which is not the object of the present study [13, 25, 31, 44, 45].
Elements of workstand for elastic abrasive cutting, (a); setup for remote thermal control of cutting process, (b); a thermogram of the abrasive cutting made from the direction to profile of the cut-off wheel, (c); a thermogram of the abrasive cutting made from the direction to full-face of the cut-off wheel, (d).
Special attachment is developed, which is fixed to the main carriage of a combined lathe, having a device for step-less adjustment of rotational frequency workpiece to perform the elastic abrasive cutting process [46, 47]. In this way, a constant rotational frequency of the cut-off wheel can be provided and adjust the amount of compression power
Cut-off area of the workstand for elastic abrasive cutting
Setup of abrasive cutting’s remote non-destructive thermal control
Raw thermogram from the camera (3) Raw thermogram from the camera (4)
Unlike previous studies, thermographic measurement of the surface temperatures is performed simultaneously with two factory-calibrated FLIR SC660 infrared cameras (3) and (4), which work synchronously with the same or different frame rates and are located orthogonally. The cameras have a temperature range from −40°C to +2000°C, temperature sensitivity (NETD) <0.045°C and IP-link using FireWire. Matlab, FLIR ResearchIR Max and SDK softwares are used for thermal analysis and supporting cameras communication with the computer (6). The PASCO PS-3209 wireless sensor (5) is used in data collection mode for ambient temperature and relative humidity during thermographic measurements.
LabIR @ thermographic high-temperature applications paint, with high mechanical resistance for long-term uses and high emissivity is sprayed to cover the entire work surface of the workpiece, the cut-off wheel, and exposed metal parts of the equipment. The layer paint thickness is measured by TROTEC BB20. Infrared cameras are located in isolating boxes with IR windows (shown in Figure 3). The outside of the boxes is also coated with paint to minimize the reflections from cameras.
A problem in the quantitative thermographic control of elastic abrasive cutting is the identification and suppression of thermal reflections in thermograms. The approach for thermal measurements of the process at an angle from 40 to 60″C was applied. Cold image subtraction and/or background subtraction is used as image processing methods for reflection reduction in thermograms.
After conducting the experiments for thermographic measurement to verify the calculated maximum temperatures of the cut-off wheel, workpiece, and cut piece and derive the corresponding correlation dependencies, the need to use a second infrared camera was eliminated. For the needs of elastic abrasive cutting online thermographic quality monitoring, only one camera is sufficient (camera (3) in Figure 3b.
Thermographic measurements were also performed with other approaches, which is not part of the present study. These relate to quantity thermography, such as the use of IR polarizing filters and deep learning to assess the condition of the elastic abrasive cutting process.
IRT used to detect the cut-off wheel wear can help abrasive cutting process automation and dynamically control.
The introduction of an online thermographic inspection system allows continuous monitoring of temperature evolution and thus prevents damage to the workpiece or machine. The following are illustrated possible information criteria for use in such a system.
Figure 4 illustrates the possibility of the IRT system to measure and record the surface temperatures (optional maximum, minimum, average values) in the camera field of vision. Areas (regions of interest—ROI, lines, polygons, etc.) can be selected to identify the temperature distribution and evolution in the process of abrasive cutting in the form of graphs. Such a local inspection of the change in surface temperature significantly increases the visual resolution of the selected area. This visualizes the momentary disturbances from the spark’s temperatures. Figure 4a shows the temperature curves for the marked lines on the workpiece and the cut piece in a direction transverse to the workpiece axis and close to the cutting area. The temperature profile longitudinally on the axis of the workpiece in the area of the marked line is shown in Figure 4c. The temperature profiles for different lines passing through the axis of the cut-off wheel show the change in surface temperature near the cutting area and at the farthest end from this area. Figure 4d shows the regions of interest (ROI) for the workpiece, the cut-off wheel, and the cut piece whose maximum temperatures are measured.
Thermograms image with chosen regions and temperature distribution along with selections. (a) Thermogram from camera
Due to the lack of a standardized format for reading IR images, software for processing and computer analysis of thermographic images has been developed. So thermal images can be processed regardless of what type of camera they were shot. The wear of the cut-off wheels has been checked. For this purpose, they are divided into four categories: standard (new cut-off wheel, as a reference), slightly worn, critically worn, and worn, which can no longer be used. One or another classification can be prepared on the basis of different criteria for different applications of elastic abrasive cutting. During data processing, areas with elevated temperatures and possible causes of wear are identified. Thus, on the basis of the initial thermal histograms, criteria for diagnosing and evaluating the resources of the cut-off wheels are formed.
The thermal histogram family (according to the camera view of vision) of the entire thermogram or the thermal histogram family of a selected ROI can be used to account for deviations in the quality of the elastic abrasive cutting process relative to a pre-selected optimal process.
Figure 5 shows (according to the camera’s view) a raw thermogram with selected ROI (rectangular area), and the area of the cut-off wheel marked with a black outline. Figure 6 shows a raw 3D thermogram of the selected ROI. Figure 7 shows the family of thermal histograms for the same ROI.
Infrared image captured with a standard thermal camera.
3D thermogram of the selected ROI in
3D layered thermal histograms (a family) for IR image sequence of the selected ROI with the workpiece, cut-off wheel, and cut piece.
There are three density modes of temperature calculation in the histograms:
High: per each pixel;
Medium: average temperature using aperture size 3 × 3;
Low: average temperature using aperture size 5 × 5.
Medium and Low approximations automatically exclude any garbage colors detected inside the camera apertures.
The general form of the models describes the dependency between the workpiece temperature
where:
Factors | Factor levels | |||
---|---|---|---|---|
-1 | 0 | +1 | ||
120 | 150 | 180 | ||
1 | 2 | 3 | ||
22 | 91 | 160 |
Factor levels in the experimental design.
To build the models (4), multi-factor experiments were conducted using an orthogonal central-composite design with a number of trials
The models (4) were built using the measured values of the workpiece maximum instantaneous temperature, cut-off wheel maximum contact temperature, and cut piece temperature at the end of the cut-off cycle.
After statistical analysis of the experimental results by applying the multi-factor regression analysis method and QstatLab software [48], the following regression models for the workpiece temperature, cut-off wheel temperature, and cut piece temperature were built:
when machining С45 steels:
when machining 42Cr4 steels:
The models built extremely accurately describe the dependency between the variables and control factors. The values of the determination coefficients are
In Figures 8 and 9 the bar diagrams of measured and calculated maximum temperatures are presented, at different parameters of the abrasive cutting process for both materials with the same workpiece diameter. The maximum temperatures are the averages of five measurements for the cut-off wheel, the workpiece, and the cut piece. The error of the calculated values does not exceed 2% (under 20°C) in the worst case.
Temperature bar diagrams for different parameters of the elastic abrasive cutting of 42Cr4.
Temperature bar diagrams for different parameters of the elastic abrasive cutting of C45.
The analysis of the models built makes possible the evaluation of the effect of the operating conditions on the temperatures of the workpiece, cut-off wheel, and cut piece:
Among all factors under study, the workpiece rotational frequency has the highest effect on temperature in elastic abrasive cutting. As
As the cut-off wheel diameter
The compression force has the least effect on temperature. As it increases, the temperatures of the cut piece, cut-off wheel, and workpiece increase by 5–11%. The minimum effect of the compression force is related to the fact that when
The nature of influence of workpiece rotational frequency, cut-off wheel diameter and compression force on the temperature in elastic abrasive cutting are equal for the two materials under study (C45 and 42Cr4 steels). Nevertheless, the temperatures of cut-off wheel, workpiece, and cut piece are higher when machining 42Cr4 steel (by 4–7%), which is related to the higher hardness and strength of this material.
Each studied temperature parameter of the elastic abrasive cutting process has a specific meaning yet is insufficient for its optimum control. The optimum values of the temperatures of the cut piece, cut-off wheel, and workpiece for each material being machined will be obtained at different combinations of values of control factors (cut-off wheel diameter, compression force, and workpiece rotational frequency). Therefore, optimization by one parameter is irrelevant. Multi-objective optimization provides much more information so as to make a justified decision on the selection of optimum elastic abrasive cutting conditions. There are various algorithms for its implementation, which differ in the type and number of target parameters, as well as in the method for determining the optimal solution [45, 49]. To determine the optimum elastic abrasive cutting conditions, multi-purpose optimization was implemented as the area where the temperature parameters under study obtain minimum values were determined. The optimization problem is reduced to solving the following system of inequalities:
where
Functions
The optimum conditions of elastic abrasive cutting, providing the best combination of minimum values of the temperatures of workpiece, cut-off wheel, and cut piece, were determined by applying two methods—genetic algorithm and random search method with increasing density. The optimization problem was solved upon machining of С45 and 42Cr4 steels by using QStatLab software [48].
The defined optimum conditions of the elastic abrasive cutting process are presented in Table 2.
Steel, type | Optimization method | Control factors | Response variables | ||||
---|---|---|---|---|---|---|---|
C45 | Genetic algorithm | 150 | 2 | 91 | 863.15 | 168.53 | 199.2 |
Random search method with increasing density | 120 | 0.96 | 159.48 | 1057.03 | 133.02 | 133.02 | |
42Cr4 | Genetic algorithm | 150 | 2 | 91 | 864.56 | 176.67 | 212.20 |
Random search method with increasing density | 120 | 0.8 | 159.99 | 1034.02 | 140.97 | 146.35 |
Optimum conditions of elastic abrasive cutting.
This chapter considers the specifics of implementing the process of elastic abrasive cutting and analyzes the conditions for stabilizing the dynamic thermal phenomena accompanying it. The processes of heat generation and heat removal in abrasive cutting are generally analyzed, as well as the methods and tools applied to investigate temperature and thermal fluxes. An innovative approach to non-destructive thermal measurement and control of elastic abrasive cutting experimented for two types of structural steels by applying the methodology of planned experiment and multi-objective optimization has been proposed.
Latest trends show that there is a need to apply an automatic smart system for controlling thermal fluxes in the cutting zone so as to ensure a higher quality of machined surfaces and longer cutting tool life. This is also linked to the design of a new approach to non-destructive thermal control of abrasive cutting when developing a smart thermographic system.
The authors would like to thank for the financial support from National Science Fund under which Project No. DN 17/16 the present work was conducted.
a | cutting depth, mm |
bs | thickness of the cut-off wheel, mm |
ds | diameter of the cut-off wheel, mm |
dw | diameter of the workpiece, mm |
F | cut-off wheel compression force, N |
h | thickness of the layer being cut, mm |
L | length of the contact arc, mm |
ns | rotational frequency of the cut-off wheel, min−1 |
nw | rotational frequency of the workpiece, min−1 |
Td | temperature of the cut piece,oC |
Q | heat generated in cutting per unit time |
Qch | heat transferred to the chip |
Qd | heat generated as a result of deformation |
Qf | heat transformed from friction force |
Qp | heat transferred into environment |
Qs | heat transferred to the cut-off wheel |
Qw | heat transferred to the workpiece |
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. 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