Criteria for assessing vibration measurements.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"6351",leadTitle:null,fullTitle:"Vasculitis In Practice - An Update on Special Situations - Clinical and Therapeutic Considerations",title:"Vasculitis In Practice",subtitle:"An Update on Special Situations - Clinical and Therapeutic Considerations",reviewType:"peer-reviewed",abstract:'"Vasculitis" describes an inflammatory process that involves the blood vessels and contributes to vascular damage. Autoimmunity, infections, drugs, and malignancies have been considered among potential etio-pathogenic factors. In vasculitis, the inflammation might develop in either a systemic or an organ-specific form and might exist as an independent pathology "primary vasculitis" or as a presentation of an existing primary pathology, that is, "secondary vasculitis". This book Vasculitis In Practice-An Update on Special Situations - Clinical and Therapeutic Considerations unlike many publications in the field, uses a different evidence-based approach to organ-specific vascular inflammatory diseases. The authors highlighted the unmet needs from the 1994 Chapel Hill Consensus Conference introducing the latest clinically relevant definitions for the different forms of vasculitis revised in 2012. The identification, classification, and management of kidney disease with different types of vasculitis with an evidence-based update on proposed therapeutic strategies are presented in this publication.',isbn:"978-1-78923-699-6",printIsbn:"978-1-78923-698-9",pdfIsbn:"978-1-83881-423-6",doi:"10.5772/intechopen.69793",price:119,priceEur:129,priceUsd:155,slug:"vasculitis-in-practice-an-update-on-special-situations-clinical-and-therapeutic-considerations",numberOfPages:112,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"9213792932243386d6a3875223e8f474",bookSignature:"Reem Hamdy Abdellatif Mohammed",publishedDate:"September 19th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6351.jpg",numberOfDownloads:5348,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:2,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:3,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 20th 2017",dateEndSecondStepPublish:"July 11th 2017",dateEndThirdStepPublish:"October 21st 2017",dateEndFourthStepPublish:"January 5th 2018",dateEndFifthStepPublish:"March 6th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"36290",title:"Prof.",name:"Reem Hamdy A.",middleName:null,surname:"Mohammed",slug:"reem-hamdy-a.-mohammed",fullName:"Reem Hamdy A. Mohammed",profilePictureURL:"https://mts.intechopen.com/storage/users/36290/images/system/36290.png",biography:'Professor Reem Hamdy Abdellatif Mohammed graduated from the School of Medicine, Cairo University, Egypt, where she is currently a Professor of Rheumatology and Clinical Immunology. She is a fellow of the Royal College of Physicians and a Certified International Professional Trainer (CIPT) at the Faculty and Leadership Development Center (FLDC), Cairo University, and at the Management Development Institute, Missouri State University, USA, carrying on teaching and training on the \\"Establishment of the Evidence-Based Strategy in Medical Research and Practice.\\" Dr. Mohammed is a verified editor, reviewer, and advisory board member for several reputable international journals. She is also a member of the “Capacity Building Team\\" at Cairo University. She is the author and co-author of several books and an international speaker in the field of rheumatology and immunology. \n\nScopus Author ID: 35280107100\n\nORCID ID: ORCID logohttps://orcid.org/0000-0003-4994-7687\n\nCU Scholar account: https://scholar.cu.edu.eg/?q=reemhamdy/publications',institutionString:"Cairo University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1035",title:"Clinical Immunology",slug:"immunology-allergology-and-rheumatology-clinical-immunology"}],chapters:[{id:"63077",title:"Introductory Chapter: Vasculitis",doi:"10.5772/intechopen.79560",slug:"introductory-chapter-vasculitis",totalDownloads:955,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Reem Hamdy A. Mohammed",downloadPdfUrl:"/chapter/pdf-download/63077",previewPdfUrl:"/chapter/pdf-preview/63077",authors:[{id:"36290",title:"Prof.",name:"Reem Hamdy A.",surname:"Mohammed",slug:"reem-hamdy-a.-mohammed",fullName:"Reem Hamdy A. Mohammed"}],corrections:null},{id:"62722",title:"Pauci-Immune Vasculitides with Kidney Involvement",doi:"10.5772/intechopen.76175",slug:"pauci-immune-vasculitides-with-kidney-involvement",totalDownloads:1201,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The clinical entity of pauci-immune vasculitis encompasses a group of diseases that may involve any organ system of the body and may be fatal if left untreated. This chapter will review these diseases, with a special interest in the clinical setting of kidney involvement. Small vessel vasculitides associated with the presence of antineutrophil cytoplasmic autoantibodies in the circulation will be the main part, since the vast majority of patients with histopathological proof of pauci-immune vasculitis are positive for these antibodies. Pauci-immune glomerulonephritis often manifests with rapidly deteriorating kidney function, while it may be accompanied by systemic necrotizing small vessel vasculitis such as microscopic polyangiitis, granulomatosis with polyangiitis, or eosinophilic granulomatosis with polyangiitis. Importantly, antineutrophil cytoplasmic autoantibody specificity has been shown to be associated with distinct clinical syndromes and different prognostic profiles among patients with pauci-immune vasculitis allowing easier recognition of the disease and long-term prognosis. Each of the clinical phenotypes will be described thoroughly with respect to the criteria required for establishment of diagnosis, the specific characteristics of renal and extrarenal histopathology, the clinical picture, the therapeutic management, and prognosis in short and long terms.",signatures:"Sophia Lionaki, Chrysanthi Skalioti, Smaragdi Marinaki and John N.\nBoletis",downloadPdfUrl:"/chapter/pdf-download/62722",previewPdfUrl:"/chapter/pdf-preview/62722",authors:[{id:"213115",title:"M.D.",name:"Sophia",surname:"Lionaki",slug:"sophia-lionaki",fullName:"Sophia Lionaki"}],corrections:null},{id:"62193",title:"Immune Complex Small-Vessel Vasculitis with Kidney Involvement",doi:"10.5772/intechopen.77226",slug:"immune-complex-small-vessel-vasculitis-with-kidney-involvement",totalDownloads:1028,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The term immune complex small-vessel vasculitis encompasses anti-glomerular basement membrane disease, cryoglobulinemic vasculitis, IgA vasculitis and hypocomplementemic urticarial vasculitis. These disorders affect predominantly small vessels, and renal involvement is frequent. In this chapter, we shall discuss thoroughly anti-GBM disease, cryoglobulinemic and IgA vasculitis with respect to the criteria required for the establishment of diagnosis, the specific characteristics of renal histopathology, the clinical picture, prognosis, and therapeutic management.",signatures:"Smaragdi Marinaki, Chrysanthi Skalioti, Sophia Lionaki and John N.\nBoletis",downloadPdfUrl:"/chapter/pdf-download/62193",previewPdfUrl:"/chapter/pdf-preview/62193",authors:[{id:"189888",title:"Prof.",name:"John",surname:"Boletis",slug:"john-boletis",fullName:"John Boletis"}],corrections:null},{id:"60045",title:"p53 and Vascular Dysfunction: MicroRNA in Endothelial Cells",doi:"10.5772/intechopen.75461",slug:"p53-and-vascular-dysfunction-microrna-in-endothelial-cells",totalDownloads:1075,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"In many cancer cells, p53 gene is mutated and accumulated, which is considered as a mechanistical target of tumorigenesis. The role of p53 in non-cancerous cells has been focused on, since p53 activation diversely affects as human diseases, including vascular dysfunctions. p53 regulates vascular events, including vascular inflammation and senescence as well as cardiac dysfunction. Many researchers also have paid attention to the role of noncoding RNAs (ncRNAs), especially small-sized microRNAs (miRNAs) for the last decade and their noble biological cellular functions have been discovered. miRNAs expressed in endothelial cells (endothelial miRNAs) have been shown to control vascular events. Firstly, the importance of p53 in a variety of vascular events, such as vascular inflammation and senescence, are summarized. Secondly, the way to regulate miRNAs by p53 and the involvement of miRNAs on p53 function are demonstrated. Finally, several endothelial miRNAs that have important roles are focused on. The aim of this chapter is to understand the role of p53 in vascular diseases in the view of endothelial cell biology and the contribution of miRNAs related to p53.",signatures:"Munekazu Yamakuchi, Sushil Panta and Teruto Hashiguchi",downloadPdfUrl:"/chapter/pdf-download/60045",previewPdfUrl:"/chapter/pdf-preview/60045",authors:[{id:"217082",title:"Associate Prof.",name:"Munekazu",surname:"Yamakuchi",slug:"munekazu-yamakuchi",fullName:"Munekazu Yamakuchi"},{id:"243041",title:"Dr.",name:"Sushil",surname:"Panta",slug:"sushil-panta",fullName:"Sushil Panta"},{id:"243042",title:"Prof.",name:"Teruto",surname:"Hashiguchi",slug:"teruto-hashiguchi",fullName:"Teruto Hashiguchi"}],corrections:null},{id:"59613",title:"Buerger’s Disease: Clinical Aspects and Evidence-Based Treatments",doi:"10.5772/intechopen.74603",slug:"buerger-s-disease-clinical-aspects-and-evidence-based-treatments",totalDownloads:1090,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Buerger’s disease (thromboangiitis obliterans) is a nonatherosclerotic, segmental, occlusive, and recurring progressive inflammatory form of vasculitis that most commonly affects the small- and medium-sized arteries, veins, and nerves in the upper and lower extremities. The cause is unknown, but it is most common in young men with a history of tobacco abuse. It is responsible for ischemic ulcers and extreme pain in the hands and feet. In many cases, notably in patients with the most severe presentations, there is no possibility of improving the condition with surgery (limb revascularization), and therefore, alternative therapies (e.g., sympathectomy, pharmacological agents, and many others) are used. This chapter discusses clinical aspects of Buerger’s disease and evidence-based treatment available currently.",signatures:"Daniel Guimarães Cacione",downloadPdfUrl:"/chapter/pdf-download/59613",previewPdfUrl:"/chapter/pdf-preview/59613",authors:[{id:"216255",title:"Ph.D.",name:"Daniel",surname:"Cacione",slug:"daniel-cacione",fullName:"Daniel Cacione"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"9104",title:"Lupus",subtitle:"Need to Know",isOpenForSubmission:!1,hash:"3bf7e412a25b5e723ece6658aaf36917",slug:"lupus-need-to-know",bookSignature:"Reem Hamdy A. Mohammed",coverURL:"https://cdn.intechopen.com/books/images_new/9104.jpg",editedByType:"Edited by",editors:[{id:"36290",title:"Prof.",name:"Reem Hamdy A.",surname:"Mohammed",slug:"reem-hamdy-a.-mohammed",fullName:"Reem Hamdy A. 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El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"217045",title:"Dr.",name:"Arnold Forkuo",middleName:null,surname:"Donkor",fullName:"Arnold Forkuo Donkor",slug:"arnold-forkuo-donkor",email:"forkuo3@gmail.com",position:null,institution:{name:"Kwame Nkrumah University of Science and Technology",institutionURL:null,country:{name:"Ghana"}}},{id:"303360",title:"Dr.",name:"Evelyn",middleName:null,surname:"Asante-Kwatia",fullName:"Evelyn Asante-Kwatia",slug:"evelyn-asante-kwatia",email:"emireku@yahoo.com",position:null,institution:null},{id:"309974",title:"Prof.",name:"Abraham Yeboah",middleName:null,surname:"Mensah",fullName:"Abraham Yeboah Mensah",slug:"abraham-yeboah-mensah",email:"aymensah@yahoo.com",position:null,institution:{name:"Kwame Nkrumah University of Science and Technology",institutionURL:null,country:{name:"Ghana"}}},{id:"347910",title:"Mr.",name:"Lord",middleName:null,surname:"Gyimah",fullName:"Lord Gyimah",slug:"lord-gyimah",email:"lordgyimah36@gmail.com",position:null,institution:{name:"Kwame Nkrumah University of Science and Technology",institutionURL:null,country:{name:"Ghana"}}}]},book:{id:"10356",title:"Natural Medicinal Plants",subtitle:null,fullTitle:"Natural Medicinal Plants",slug:"natural-medicinal-plants",publishedDate:"May 11th 2022",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10264",leadTitle:null,title:"Click Chemistry",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tThe goal of the book is to give the reader an overview of a field related to click chemistry. This book aims to provide information about click chemistry to the synthesis nano/microstructures, click chemistry for drug delivery nanosystems, and applications of click reactions in environmental technologies. The book welcomes submissions written by authors in the field of experimental methods and critical reviews from multi-disciplines such as chemistry, environmental chemistry, pharmacy and materials science.
\r\n\r\n\tAmong others, welcome topics are in situ click chemistry, classification of click chemistry, click chemistry in polymer science, click chemistry in materials science, click chemistry reactions in medicinal chemistry and pharmaceutical applications, click chemistry in environmental chemistry applications and pollutants, chemical sensors sensor based on click chemistry, photoelectrochemical sensor based on click chemistry, wastewater treatment, nanoadsorbent, hydrogel networks.
\r\n\r\n\tAll interested authors are welcome to focus on recent studies, industrial applications, and new technological developments on click chemistry in nanotechnology.
\r\n\t
To improve safety and performance, manufacturing companies have been considering the adoption of advanced technologies, as stipulated in Industry 4.0 reports. These technologies include IoT/IIoT, big data and analytics, smart factory, cyber-physical systems (CPS), and interoperability of automation equipment. Over the last few years Artificial Intelligence (AI) has comeback with a vengeance not seen before in any of modern technology implementations. AI and IoT/IIoT are driving forces in Industry 4.0 with applications in manufacturing, oil and gas, utilities, banking, aerospace and defense, healthcare, retail, telecommunications, smart cities, and transportation. Artificial intelligence’s impact on manufacturing can be organized into the following main areas: product quality and yield, predictive maintenance, collaborative robots, generative design, supply chain management and safer work environment.
While there are a lot of papers written about predictive maintenance and AI applications [1, 2, 3, 4, 5, 6, 7], but there is a lack of machine health predictive maintenance teaching and training models for university level courses as well as facilities for providing hand-on interactive experiences in the use of IoT/IIoT and Industry 4.0 platforms. To address this need SEPT created a learning factory and a framework for learning these technologies as well as designed and developed machine health monitoring models.
To reinforce hands-on learning two key aspects of machine health monitoring are presented in this chapter: foundational technologies such as sensors for predictive maintenance, IoT and IIoT ecosystem, and CPS monitoring tools; the second aspect covers in detail the design, development, and implementation of machine health learning models along with implementation of AI tools for real-time data generation, preprocessing it and sending to the cloud or local server for data analytics and visualization. These models provide an opportunity for developing and learning multidisciplinary and multi-capability skills in a laboratory setting.
The engineering education is witnessing revolutionary changes in response to the huge demand for engineers with high industry 4.0 competencies. Engineering graduates will need to learn IoT and IIoT as the foundation for implementing Industry 4.0 concepts in industrial operations. The school of Engineering Practice and Technology (SEPT) at McMaster University has recently made huge effort to integrate IoT, IIoT and Industry 4.0 in the undergraduate and graduate curriculum [8].
In the undergraduate Automation Engineering Bachelor of Technology offered by SEPT, a new smart systems specialization is introduced in the fourth year, where the offered courses focus on IoT. The other option is the Industrial Automation specialization. A new introductory IoT course (SMRTTECH 3CC3) was developed and offered for the first time at the 3A level in the fall of 2019. The purpose of this course is to introduce the students to the fascinating world of IoT before choosing their specialization for the fourth year and before going to their mandatory co-op training [9].
Another effort by SEPT is the formation of a Cyber-Physical Systems Learning Centre that focuses on implementing Industry 4.0 concepts for teaching, training, and research at McMaster University [10, 11]. The Centre includes a series of specialized learning labs and the SEPT Learning Factory that allow the development of various theoretical and technical skills needed for product production. The Learning Centre complements students’ qualifications and abilities by providing new technical skills that emphasize the inherent multidisciplinary nature of smart systems and advanced manufacturing.
Machine health monitoring is a key opportunity to improving and maintaining profit. In manufacturing industries, it is expected that when a machine is started it should perform as designed and used for an application and run for hours, months and years without any breakdown interruptions. Vibration monitoring along with power and sound monitoring are a significant source of machine health information. By adopting the use of new technologies such as IIoT can lead to improved manufacturing productivity with more reliability and even reduce skill requirement needs. However, developing and implementing these applications does require a new breed of engineering technology graduates. IIoT offers an opportunity for ubiquitous detection of machinery faults that can lead to prescriptive maintenance plans.
During operation mechanical faults in machines produce unique vibrations which depend upon the geometry of the machine elements such as shaft, spindle etc., and shaft rotation speed, in addition to the obvious load factor. There is a huge list of mechanical faults that can be detected with vibration data collection and performing an analysis on it. This list includes imbalance; misalignment; bent shaft; rubbing shaft; bearing defects; loose parts; and belt drive faults etc. For example, recently a pump servicing company has identified a few major causes of vibration [12]. Their report lists six main causes of pump vibration problems and anyone of those could take a pump out of service for unplanned and expensive repairs. A pump’s poor performance can be due to one of the following vibration problems: pump cavitation; bent pump shaft; pump flow pulsation; pump impeller imbalance; pump bearing issues; and misalignment of the shaft.
Many organizations use manual and off-line inspection tools for their reliability and maintainability programs while IIoT provides an opportunity to perform these tasks on-line in real-time time. IoT alone is projected to deliver between $1.9 and $4.7 trillion of economic value by 2025. The IIoT for asset monitoring is expected to produce $200-$500 billion in economic value by 2025 [13]. These technologies enable machine health monitoring (or also referred as condition monitoring) and predictive maintenance to optimize maintenance processes and improve operating costs. This type of monitoring is expected to help manufacturers to optimize their operating costs by predicting the failure of critical machines and their components to achieve high efficiency and reliability.
According to one market report the global machine health monitoring market size, driven by on-premises deployment, is estimated to reach USD 3.9 billion by 2025 [14]. On-premises application development give organizations control over their data and systems to protect the critical information. Whereas deployment on a remote cloud has its advantages and disadvantages related to hardware, software, deployment, and maintenance costs. Another factor that needs to be considered carefully is storage capacity at the local and remote server sites. Cloud-based deployments do provide organizations with enhanced accessibility and scalability, 24/7 service speed, and IT security measures that cannot be implemented due to lack of resources at the local site. In part the growth of this market is being driven by the availability of secure cloud platforms. An overall IoT/IIoT ecosystem with elements shown in Figure 1 would be required. This type of ecosystem has been established at the SEPT Learning Factory to demonstrate these technologies [15].
IoT/IIoT ecosystem overview.
Online machine health monitoring systems can be implemented for critical equipment, such as motors, turbines, blowers, pumps, and compressors, that have an immediate impact on the productivity of plants as well as human and machine safety, and the environment. Current monitoring systems include a sequence of sensors permanently mounted on the critical machines for sensing. The sensors are connected to microcontrollers, single board computers, and/or PLCs, and generated data can be sent to a central server of a plant or to an outside cloud platform such as PubNub, Google, Amazon, and ThingsBoard etc. The sensor data is sent to the plant operators through either a wireless network or a cabled network and displayed on monitors. This can be accomplished in two manners as depicted in Figures 2 and 3. UniS is the UniSphere 1 local platform at SEPT hosting MQTT broker, Figure 4, as well DDS server.
A typical IoT model used in SEPT learning factory.
An IIoT model used in SEPT learning factory.
MQTT broker local and remote servers.
Vibration, sound pressure, motor current, magnetic field, temperature, and oil quality are some of the more common sensors used for condition-based monitoring for predictive maintenance tasks. Most systems will only employ some of these sensors based on potential critical faults detectable by the selected sensor. Vibration sensors fall in this category.
This type of sensor is used for general purpose applications for vibration and shock measurements. They are available as digital or analog devices and designed using different principles such as piezoelectric, piezoresistive and capacitive. These components are used to convert the mechanical motion caused in the device into an electrical signal. Accelerometers are the most used vibration sensors for predictive maintenance of turbines, pumps, motors, and gearboxes. The piezo vibration sensors are considered as the gold standard in this category. An important category for acceleration measurements are the MEMS sensors. MEMS accelerometers and microphones are highly suited to battery-powered predictive maintenance systems due to their small size, low power consumption, and high-performance capabilities [16].
Strain gage is a sensor whose resistance changes with an applied force. From resistance change of the
Velocity sensors are used to measure a frequency range of 1 – 1000 Hz. The sensors are suitable for vibration monitoring and balancing applications on rotating machinery. This type of sensor has a lower sensitivity for vibrations with high frequencies than accelerometers and is therefore less susceptible to overload. These sensors are used for high-temperature applications like above 700°F.
The main functions of the gyro sensor for various applications are angular velocity sensing, angle sensing, and control mechanisms. Gyroscope sensors are used in the car navigation systems, electronic stability control systems of vehicles, drones and radio-controlled helicopters and robotic systems. There are different types of gyros for different applications and they are: ring laser; fiber-optic; fluid gyro; and vibration gyros. Most used, vibration gyro sensors, use either piezoelectric or silicon transducer element in their construction. Gyro sensos, when used in conjunction with accelerometers, can keep track of the orientation of the system, thus providing a complete picture of the vibrating system.
Most used non-contact vibration sensors types fall in the following categories: microphone or acoustic pressure sensor; laser displacement sensor; and eddy current or capacitive displacement sensor. Non-contact vibration sensors can be deployed on both new and old machines, even when they are hot, wet, in a hard-to-reach places or too small for other sensor types.
Predictive maintenance as evolved over the years now is considered as an important IIoT application that can be implemented fairly-easily. It also connects with Industry 4.0 paradigm, big data and analytics, and machine learning. Over the years it has evolved from reactive, preventive, and reliability-based maintenance operations [17]. Many new online sensors are being introduced each year. IIoT enables machine condition control in the following manner: collection of real-time sensor data, perform data analytics, followed by corrective action either by an operator or autonomously by the machine. In this context data analytics is related to converting data into actionable information and can have implications for predicting future events such as predictive maintenance. Now with the revised promise of AI technology the predictive maintenance can evolve to prescriptive maintenance where a smart machine can help avoid the predicted failure. In essence the following steps are required to implement such program: identifying critical assets, creating a database of relevant information, understanding failure modes, developing models for predicting failure modes, test the predictive model (s), and deploy for real-time operations as outlined above.
Even though there are many new sensors available for monitoring and control, there are many areas where manual steps are still required for maintenance activities due to lack of appropriate effective sensors. Thus the means of data acquisition can be multimodal. It can be obtained from samples collected manually and analyzed in the laboratory, monitored in real time with online sensors, acquired using portable data collectors, or examined by operators and engineers. In addition other tests and inspections at the machine site can help complete the picture and establish greater confidence in what’s happening now (or not happening).The IIoT and AI technologies cannot make all other forms of condition monitoring obsolete, but they are powerful enablers. Consider an example in a machine shop with CNC routers, lathes, EDM machine, and metal 3D printers etc. Over a period of their operation the following can change: machine age which can lead to changing vibration, heat, acoustic emissions, displacement, alignment, balance etc.;oil and filter age; temperature and humidity; load conditions; looseness of parts; and operator handling. These changes may require further monitoring and adjusting such things as: oil flow rate and temperature control; grease dosage rate and frequency; viscosity correction; additive replenishment; machine operation; maintenance and inspection requisitions. Because of this complexity it is possible to design and develop different software applications that can address the above challenges by integrating more soft and hard automation processes.
AI Machine Learning involves the following steps: identifying the data set and corresponding sensors; collecting the data; preparing the data set for training, validation and testing; choosing a model and algorithm; perform model training calculations; evaluate the model; tune the model; and deploy the model for prediction.
As mentioned above a major objective for manufacturing industries is to reduce the cost and improve safety and production. During 1980’s to 1990’s, the cutting tool was replaced based on wear of the cutting tool. But since then, tool condition monitoring systems have evolved and are used quite extensively to achieve the following objectives: early detection of cutting tool wear; maintaining a machining accuracy by providing a corrective action for tool wear; and prevention of cutting tool from breakage [18]. Using modern high precision sensors for sound, temperature and humidity,
In a recent study the authors used a MEMS installed sensor on a CNC machine with Fanuc controller to measure vibrations for maintenance purposes [19]. First, they carried out three case studies: optimal cutting values with a worn-out tool, cutting values with a new tool that breaks and does not break. After the analysis of case studies, a maintenance method was chosen according to TPM and TQM program guidelines. The analysis of the result lead to a proposed maintenance program. But the authors did not use any of the AI tools available to develop a predictive maintenance program.
In this case study a lathe is used to cut a stock bar into different size pieces. This lathe has an auto-fed bar feeder delivering 12-foot bar stock to the unattended running machine [20]. A significant number of parts were being scrapped due to irregularities in the bar, causing dimensional and finish errors. These irregularities in the bar could lead to a lot of scrap metal and damage the spindle. A commercial solution was used to install vibration sensor and connected it to the CNC control to monitor certain characteristics of the lathe. When excessive bar feeder vibration levels were detected the software would automatically signal the CNC to reduce spindle RPM until the vibration levels are acceptable to make good parts. If RPM must be reduced too much, and parts cannot be cut, an alarm was generated to inform the operator to stop the machine to remove the bar. In this case this process can be further automated, but it would require local technical resources to implement them.
To monitor vibration measurement remotely the following protocol options are available: WirelessHART; ISA100; WiFi; Bluetooth; LoRa; and Proprietary. The following factors needs to be considered in selecting the appropriate protocol: built-in security; reliability; bandwidth; power consumption; supported configurations; interoperability between vendor products; and network maintenance. Another critical factor that needs to be considered is where do you perform the calculations related to the data analytics option for the wireless monitoring system and what information is going to be transmitted wirelessly. That is where and how would you view and store the raw sensor data, see the real-time trend and historical data, and send the alarms to mobile devices and remote computers. How and where would alarm be calculated.
WirelessHART (IEC 62591) is a field proven technology with very wide installed base as it was built on HART protocol. It has been an international standard (IEC 62591-1) since March 2010. This protocol offers the following advantages: it has small defined packet structure for reduced bandwidth and interoperability; built in security; uses mesh networking to ensure reliability; and can be expanded easily. A wide variety of device types are available from many automation equipment suppliers. SEPT Learning Factory provides the following two options for student projects: vibration transmitter (Emerson) as depicted in Figure 5; and a portable machine health analyzer (Emerson). The transmitter monitors/transmits WirlessHART vibration and temperature in hard-to-reach locations. It provides complete vibration information including overall levels, energy bands, high resolution spectra, and wave forms. It provides information for bearing and gear diagnostics. The PC hosts the specialized software provided by Emerson. The WirelessHART access point easily integrates into any host via Modbus TCP with capabilities for detailed diagnostics via a commercial software suite or custom-built Software. The wired option with dashboard shown in Figure 6, and user interface software components, Figure 7, required to build the dashboard for the Haas CNC vibration and other parameters monitoring has been implemented as well.
Wireless HART sample set up.
HAAS CNC web user Interface.
On the other hand, the portable machinery health analyzer (Emerson) is used by the students working in the Learning Factory for vibration data collection and field analysis. This system can provide route vibration collection; advanced vibration analysis; cross-channel analysis; transient analysis; dynamic balancing; motor monitoring; and ODS modal analysis. It wirelessly uploads route data and corrective maintenance jobs from the field to AMS Machinery Health Manager (Emerson) for analysis and reporting. AMS Machinery Manager integrates data from multiple technologies, including vibration, oil analysis, thermography, and balancing into a single database to deliver the predictive intelligence necessary for increasing availability and reliability in the plant.
Another industrial IoT wireless machine health monitoring system with the following sensors: vibration sensor, thermocouple, AC split core current sensor, and ambient air temperature sensor is also available to the students for experimentation [21]. This low-cost device samples vibration, RMS current and temperature data and sends after a user-defined time interval over the wireless network. The vibration sensor samples 3-axis vibration data for 500 ms and then calculates RMS, Maximum, and Minimum vibration readings then combines these data with temperature values in a data packet and transmits the result to modems and gateways within wireless range. After each transmission it goes back to sleep, thus minimizing power consumption. This system uses DigiMesh® protocol, from Digi.com for wireless transmission of data, which automatically hops data from gateway to gateway until it arrives at the desired destination. The data on the other end is either received by an IoT gateway or an IoT modem, connected to local Learning Factory MQTT broker, and ultimately displayed on the dashboard designed by the students either using Grafana or Node-Red.
User Interface software components.
It is also important to take note that the overall vibration data is not always a good indicator of machine health due to the following aspects of vibration measurement: fluctuates heavily due to process changes and insensitive to other failure modes such as bearing faults, gear defects, lubrication, and pump cavitation. Since the vibration analysis is based on raw vibration data other values such as RMS, peak value and impacting g’s can be obtained as well. There are many approaches in interpreting the information from the raw vibration data. For example, contrary to claims in literature, it has been shown that RMS and peak values are good indicators of the gearbox health if used properly [22]. Another example is the analysis of vibration data from a process pump which showed that the overall vibration indicated good health of the asset while hidden in the raw data was the rising g values that indicated a bearing defect. The impacting analysis g values from the raw data can provide useful information for the following types of faults: bearing faults, gear defects, lubrication, and pump cavitation [23].
20816-1 provides general guidelines;20816-2 covers land-based gas turbines, steam turbines and generators in excess of40 MW, with fluid-film bearings and rated speeds of 1 500 r/min, 1 800 r/min, 3 000 r/min and 3 600 r/min;10816-3 Industrial machines with nominal power above 15 kW and nominal speeds between120 r/min and 15 000 r/min when measured in situ; 7919-3 Mechanical vibration —Evaluation of machine vibration by measurements on rotating shafts—Coupled industrial machines; 20816-4 Gas turbines in excess of 3 MW, with fluid-film bearings; ISO 20816-5: Machine sets in hydraulic power generating and pumping plants,ISO 10816-6: Reciprocating machines with power ratings above 100 kW,Part 7: Rotodynamic pumps for industrial applications, including measurements on rotating shafts,Part 8: Reciprocating compressors.
ISO 20816-1 provides various evaluation zones: zone A, the vibration of newly commissioned machines normally falls within this zone; zone B, machines with vibration within this zone are normally considered acceptable for unrestricted long-term operation; zone C, machines with vibration within this zone are normally considered unsatisfactory for long-term continuous operation; zone D, vibration values within this zone are normally considered to be of sufficient severity to cause damage to the machine. The Table 1 provides summarizes this information for industrial machine falling with in the ISO 10816-3 standard.
>11 | Zone D | Zone D |
>7.1 | Zone D | Zone D |
>4.5 | Zone D | Zone C |
>3.5 | Zone C | Zone B |
>2.8 | Zone C | Zone B |
>2.3 | Zone B | Zone B |
>1.4 | Zone B | Zone A |
>.7 | Zone A | Zone A |
>0 | Zone A | Zone A |
Foundation | Rigid | Flexible |
Criteria for assessing vibration measurements.
ISO 10816-3:2009 is relevant to the common industrial machines and it gives criteria for assessing vibration measurements when made
In this section we describe three machine health predictive maintenance teaching and training models developed at SEPT LF. They are: Fan Fault Detection and Diagnosis (FDD); IIoT Vibration Demonstration Station; and Machine Health Monitoring and Prediction Platform.
The purpose of Fan FDD is to be able to determine faults in a mechanical system, in this case a spinning fan, and diagnose which part of the fan is faulty. It utilizes vibration and current measurements in combination with machine learning. The system uses a small computer called a Raspberry Pi, and a microcontroller (SAMD21G18A). Upon request from the Raspberry Pi, the microcontroller will record the vibration (in FFT) and current data from the fan and return it to the raspberry pi to store. The Raspberry Pi can use the data to train a neural network to make assumptions about the state of the fan.
The system is unique as it can be trained on 3 fault conditions, but it is able to output separate 4th condition which is a combination of two other conditions!
The circuit board contains a microcontroller, a SAMD21G18A, I2C for the accelerometer, ADXL345, an op-amp circuit for measuring current, and some display LEDs to give the user some feedback. The microcontroller can communicate with the Raspberry Pi through the Serial Port via USB. The firmware on the microcontroller only responds to commands from the Raspberry Pi serial port.
The program that runs on the raspberry pi is written in python. Two main programs were written for Data Collection; and Fault Detection.
The purpose of this program is to collect different datasets to later train the network. The user will run through a series of events displayed on the screen. It will ask the user to turn on the fan, run the fan in normal condition, collect data, run the fan with a weight attached to the impeller (to simulate a broken fan blade), collect data, and finally run the fan with a cover on it (to simulate a blockage) and collect data. Once all of this has run it will automatically create a dataset and train the neural network with the data. The dataset for each fault condition is an FFT (calculated on the microcontroller) + the current measurement. Using the datasets, the data collection will run a program called “trainNN.py” which will output an neural network file type of “nn” which can be later used to determine the fault of the fan.
The purpose of this program is to use a previously trained neural network that used the data that was collected, and to determine the current state of the fan. The program will continuously run to give the state of the fan as an output on the raspberry pi. Since the training data collected was 3 individual fault conditions (including healthy) those are the states that the network will output.
With this vibration station the main purpose was to communicate the benefits of IIoT also known as “Industrial Internet of Things”. At the time of development in 2016 this was a very new concept and so we thought we would showcase how it can be used in practice. Our system had a variety of components, starting with of course the mechanical/electrical but the bigger focus really was on the software front. In terms of software the system could be broken down into 3 major components, a frontend dashboard, a communications service for message passage, a data processing model to predict faults in the system.
For the mechanical build structure system, the goal was simple. We needed to create a structure to which we could mount the following components:
Motor with axle
PLC for motor control
Capacitive touch trigger
Power supply
DAC (Arduino used)
Accelerometer (sensor #1) *
DC current sensor (sensor #2) *
We also needed a method of being able to simulate a “failure event” the way we went about this was by creating an axel to which we could add counter weight to replicate the motion if a bearing had been torn due to overuse. By adding additional weight, we can create the level of counterbalance needed to test the flexibility of our predictive model later. Our result is as follows Figure 8.
LF vibration demonstration.
Our electrical system was also very straightforward, we simply needed to be able to provide the various currents required by all the system components. In the end we had the following devices actively connected in our system, in order of communication direction Figure 9.
Block diagram of the electrical connections for the Vibration Station.
Our first objective for our IIoT vibration station was to get the data flowing and network so that we can visualize the raw information coming from the system. Our goal was to get the data front the sensor to a networked user interface that could be accessed anywhere from the world. This means we need a web app, data acquisition tool, and most importantly a messaging system. For our case we used MQTT, a middleware-based messaging system that allows for pub/sub based information transfer. In the end our data flow looked like follow Figures 10 and 11:
Vibration Station data flow components.
Vibration Station user Interface.
After having accomplished all the other requirements to get data from our system, as well as get that data visualized and networked, our main goal was to create a predictive maintenance model. We used our weighted offset assembly to create 2 main datasets, one where there is no imbalance and second where we add some offset weight and capture the “fault” labeled data. The difference between the FFT output of each can be seen in Figures 12 and 13, and as seen there is not a noticeable difference visually in the two plots.
FFT plot with No load on the motor.
FFT plot with imbalance load on the motor.
Our first step was a vanilla neural network approach with no preprocessing, we fed the raw current and vibration data into a multi layered (3) neural network and trained it on both the good and bad data with the appropriate labels.
This approach turned out to be flawed, our main thinking in regards to this is that the neural network did not have enough learning capacity to map the given data into the frequency domain, where the faults are clearly indicated. The neural network would first need some sort of temporal mapping, and then on top of that also learn to differentiate between fault and no fault. To combat this issue, we attempted to preprocess the data through an FFT, this would map the data into the frequency domain and THEN through the neural network differentiate the data into it is given label.
This new approach worked much better, with a very high success rate in terms of predicting faults. The training also took only 5 minutes one a laptop, what this means is that the model can be trained on edge and in real time to continuously update itself as the system slowly degrades. Our simple neural network model is given as follows:
An important takeaway from this project was around the structure of IIoT in a realistic setting as well as a realization of the various benefits IIoT brings, like the ability to visualize and see what is going on in our system in real time, from anywhere. This ability of constant perception into the system combined with a data processing model creates an approach for predictive maintenance that is very powerful, low-cost, and useful in active learning settings.
An Advanced Predictive Learning Station has been developed, with an embedded vibration sensor and other sensors, that analyses a system for faults and transmits information wirelessly. Students will be able to report errors such as general imbalances, mechanical failure, resonance, electrical faults, and critical speeds. It can be easily extended to further application demonstrations such as bearing faults, AI modeling using multiple sensor inputs and analysis.
The station design is based on an open architecture. It is designed to give students access to all potential avenues for learning and experimenting. The lab resource materials (designs, schematics, code) are all provided to the students. Documentation aside, students are also given access to as many elements on the learning station of the system as possible. There are oscilloscope probe points on the station to allow the students to view the trace of various signals as well as given control over many other aspects of the station. They can easily control the motor speed, explore all the signals of the system (even if they are not related to the lab). They can view the output of the encoder and view signal from the vibration sensor.
The lab hardware is shown in a block diagram below. A detailed point by point description follows to express the high-level function of the components in the system (Figure 14).
Machine health Hardware Station layout.
Because of the signal access points the students can using an oscilloscope to view the FFT plot on the screen. Most modern oscilloscopes have this feature built in. The students should clearly understand how the sampling system of the oscilloscope relates to the standard parameters of an FFT. These should first be demonstrated by feeding a 1khz sine wave or square wave into the oscilloscope.
In this example we are using 15000 samples at a sampling rate of 7.5 kbps on a 1 kHz sine wave. We are using 4096 frequency bins. From this experiment students will quickly see the application of an FFT in determining frequency components in complex time domain signals (Figure 15).
FFT plot of 1 kHz sinewave oscilloscope output.
Once an understanding of the signal has been achieved, students can then do a lab experiment where they use the microcontroller to sample the incoming signal and do basic amplitude analysis on the signal. This can then be expanded to sampling on all three channels. A simple flow of sampling is demonstrated below. This sampling is done for single shot analysis, this is not a “real-time” sampling system. Realtime FFTs are typically done on FPGAs or systems with much more bandwidth capabilities (Figure 16).
Flow of sampling data from the machine Health Station.
The signal goes through an amplifier and buffer circuit to put it in the range of the ADC. The ADC is an I2C ADC, this is a better alternative to the micro-controller on board ADC because it is higher resolution. The microcontroller then samples the ADC at a known sampling rate (usually 2 kHz) and puts the samples into a buffer. This buffer can then be used for analysis.
If the students have a method of viewing the ADC buffer in a graphic way, it can help them develop the application faster. A good solution for this is using Python to receive serial/UART data from the micro-controller and plot it on a PC.
The final section of experimentation is designed to show students that for any data to be useful it must be provided to an end user who cares about it and it must be presented properly. The system of choice for communication is MQTT 5. This allows for the simplest possible method of publishing the resulting data from the microcontroller for external use (Figure 17).
Machine health monitoring data flow.
An InfluxDB can be used as the receiving database. It is important to display the data to the user and it is also important to store that data. If the data is stored it can later be used for developing machine learning based decisions. The historical data can also be used for long term vibration analysis which is the most important element in preventative maintenance.
This experiment can be extended to have students send the raw sampling data over Wi-Fi. What students will quickly realize (depending on their lab setup) is that it is much more “power expensive” to send raw data over Wi-Fi as compared to processing the data and sending the compressed details.
The complete lab setup is featured below. The lab is designed to be stackable and easy to store. The main design feature of the system is the vibration isolation between the motor and the frame. If the motor is not correctly isolated, most of the vibration will be absorbed by the frame. This is conducive to real world implementation because motors are usually mounted on some type of vibration isolation barrier (Figure 18).
Machine health monitoring station hardware setup.
This lab is designed to help students realize IoT and Industry 4.0 applications at an accelerated rate. There are some components of this application that were not explored. Students should be given brief readings to help them understand these additional components of vibration analysis.
Variable speed drives will provide different vibration results at different RPMs; therefore, motor speed is reported.
Varying loads on a motor (mixers, pumps, crushers) can provide data that is much more difficult to analyze due to the large volume assorted frequency components.
Usually motor failures do not occur as one large change in a vibration peak but, rather, the slow increase of a particular peak that represents some wear or imbalance in the motor.
A monitoring system should also consider system maintenance. If a component in the drive stage is replaced (a blade in a sawmill for example) the results will vary after the blade is change. There is no way to know the blade is changed without some user input or long-term data analysis. If there are students who work through this application at a faster rate, they can be asked to implement current monitoring as well.
The term IoT was coined in 1999 and it led to the evolution of IIoT enabled by other technologies that were being developed independently of each other. These technologies include such as: cyber-physical systems & cybersecurity; edge and cloud computing; mobile technologies; machine-to-machine communication; 3D printing; advanced robotics; big data; RFID technology; and AI. The SEPT Learning Factory is state-of-the art facility at McMaster University for the demonstration of integration of these technologies as well as development of educational/training material and resources, new technologies, and applied research.
Based on AI modeling the Fan Fault Detection and Diagnosis System described is able determine a fault state that was not included in training the AI model. The IIoT Vibration Demonstration Station using the neural networking model can detect the machine fault in real-time and publish the outcome on a dashboard connected via MQTT platform. The Machine Health Monitoring and Prediction Platform on the other hand combines the best features of the last two models for advanced predictive maintenance learning concepts and real-time demonstrations. This station has been developed, with an embedded vibration sensor and other sensors, that analyses a system for faults and transmits information wirelessly. Students will be able to report errors such as general imbalances, mechanical failure, resonance, electrical faults, and critical speeds. It can be easily extended to further application demonstrations such as bearing faults, AI modeling using multiple sensor inputs and analysis.
In this chapter we have described IIoT machine health monitoring foundations, models and applications for education and training. We have also illustrated how these models can be extended for development of predictive maintenance using AI technology.
This project is partially funded by Future Skills Centre, Canada.
Central nervous system metastases are a common and often lethal manifestation of malignant melanoma, with a median overall survival of as little as 4.7 months based on a study of patients diagnosed between 1986 and 2004 prior to the era of effective systemic therapy [1]. Although both cutaneous and mucosal melanomas have a high propensity for CNS dissemination, this is almost unheard of with uveal melanoma despite the close anatomical proximity of the eye and brain [2]. CNS involvement often causes neurological deficits and functional impairment. Localised therapies, such as surgical excision and stereotactic radiotherapy, are applicable to only a minority of patients. However, stereotactic radiation therapy is able to overcome the relative radio-resistance of melanoma by delivering extremely high doses of radiotherapy with little damage to surrounding brain tissue [3]. It is also increasingly appreciated that stereotactic radiotherapy may drive immunogenic cell death and this can lead to regression of non-irradiated lesions via immune priming and the ‘abscopal’ effect [4]. Radiotherapy can upregulate tumoural PD-L1 expression and can lead to increased T-cell infiltration of tumours with increased proinflammatory cytokine levels [5, 6]. This potential synergistic interaction between stereotactic radiotherapy and immunotherapy could be exploited and this is being explored in current clinical trials (PERM trial NCT02562625). Symptomatic patients require corticosteroid therapy to reduce peri-lesional vasogenic oedema and control neurologic symptoms in the short-term. It is suspected that high-dose corticosteroids prevent immune activation and attenuate the benefit of immune checkpoint blockade.
The blood brain barrier comprises of endothelial cells, astrocytes and pericytes. Usually the passage of molecules from blood to the brain parenchyma is limited under physiological conditions [7]. However, research has shown that activated T-cells can cross the blood–brain barrier - raising the possibility of treatment using immunotherapy [8]. The endothelial cells of the blood brain barrier in brain metastases are thought to be able to initiate an inflammatory cascade that activates immune cells [9]. Berghoff et al. have shown, using immunohistochemical analysis of melanoma brain metastases, that three-quarters of these lesions exhibit CD3+ tumour-infiltrating-lymphocytes and tumour cells were PD-1 positive in half of cases [10] ( Table 1).
Drug | Target | FDA approval date | Treatment schedule |
---|---|---|---|
Ipilimumab | CTLA-4 | March 2011 | 3 mg/kg administered intravenously every 3 weeks |
Pembrolizumab | PD-1 | December 2014 | 2 mg/kg administered intravenously every 3 weeks or 200 mg every 3 weeks/400 mg every 6 weeks |
Nivolumab | PD-1 | September 2014 | 3 mg/kg administered intravenously every 2 weeks or 240 mg every 2 weeks/480 mg every 4 weeks |
Immunotherapy and treatment schedule.
In contrast to carcinomas, such as breast and lung, melanoma brain metastases display a diffuse lymphocytic infiltrate throughout the tumour mass as opposed to a stromal infiltrate [11].These pathologic data provide strong evidence that adaptive immune responses can be active in the distinct microenvironment of the brain.
Lepto-meningeal metastases are a deadly and feared complication of malignant melanoma and also occur commonly in breast and lung cancers. They are common in haematological malignancy but much rarer in solid tumours where they usually manifest in the presence of advanced metastatic disease in multiple organ systems. Lepto-meningeal metastasis, also sometimes known as neoplastic meningitis, occurs when cancer cells disseminate to the arachnoid and/or pia mater covering the central nervous systemic tissue in the brain and/or spinal cord. They typically cause rapidly-progressive, and often fatal, neurological deficits due to infiltration of cranial nerves, spinal cord and nerve root compression (radiculopathy), symptoms of meningitis and raised intracranial pressure. Treatment is usually supportive and there is very little evidence for any anti-cancer treatment being effective although intra-thecal chemotherapy has been used as has cranio-spinal radiotherapy which is poorly tolerated in adults.
The vast majority of clinical trials for metastatic melanoma exclude patients with brain metastases, and certainly those with symptomatic lesions. Therefore, there is a paucity of clinical evidence to guide decision making in terms of therapeutic options for this patient population. The current clinical evidence base comprises small, retrospective studies. The majority of patients with metastatic melanoma will develop brain or lepto-meningeal metastases at some point in their disease trajectory [12], therefore this chapter will provide a good summary to help clinicians to understand and manage this group of patients.
The therapeutic options for patients with metastatic melanoma, previously restricted to dacarbazine chemotherapy (DTIC, alkylating agent) [13] and immunotherapy with high-dose intravenous interleukin-2 [14], have expanded to include immune checkpoint inhibitors and BRAF targeted therapy in recent times and the outlook has become somewhat less guarded with long-term survival being achieved in a proportion of patients. Importantly, in terms of randomised, comparative large-scale clinical trials no such evidence exists for DTIC or IL-2 despite FDA approval in 1975 and 1998 respectively. Immune checkpoint inhibitors are monoclonal antibodies that disrupt the CTLA-4/CD28 and PD-1/PD-L1 interactions, and by so doing, lead to improvements in T-cell priming by dendritic cells and cytotoxic T-cell effector function respectively. These treatments, such as ipilimumab (anti CTLA-4) and pembrolizumab (anti-PD-1), attenuate T-cell inhibitory signals and generate enhanced, sustained and powerful anti-melanoma immune responses that can be associated with durable disease control. It is noteworthy that the first systemic therapy proven to confer a survival advantage in metastatic melanoma was the anti CTLA-4 antibody ipilimumab and this was the first time in a randomised clinical trial that an increase in overall survival had been achieved in this disease [15]. The comparator group in this trial was treatment with an HLA-A2 restricted gp100 peptide vaccine not placebo and patients had received prior chemotherapy or IL-2. Toxicities of ipilimumab can be severe and unpredictable and in the pivotal study, the treatment-related death rate was 2.1% although this has diminished over time as physicians’ experience and patient education improves. However, with ipilimumab monotherapy only approximately one in five patients achieve long-term overall survival and patients with high volume metastatic disease, elevated serum lactate dehydrogenase levels, low serum albumen, rapidly progressive course and brain metastases seldom derive benefit benefit [16]. In previously untreated metastatic melanoma patients, high-dose ipilimumab monotherapy (10 mg/kg) in combination with dacarbazine chemotherapy outperformed chemotherapy in terms of overall and progression-free survival and to a lesser extent objective response rate [17]. From the clinical perspective, the United Kingdom [18] National Institute for Health and Care Excellence (NICE) approved Ipilimumab for the treatment of metastatic melanoma in 2012 [19], followed by Pembrolizumab and Nivolumab that target the PD-1 axis in 2015. Combination immunotherapy with concurrent ipilimumab and nivolumab has also been available since 2017 for the treatment of metastatic melanoma with favourable outcome compared to ipilimumab monotherapy. This clinical trial was, however, not sufficiently powered to definitively determine if combination immunotherapy was superior to nivolumab monotherapy [20]. Ipilimumab and nivolumab can achieve objective radiologic responses rates of approximately 60% and the likelihood of 5-year overall survival is 53%. These agents, especially anti PD-1 monotherapy, are better tolerated than chemotherapy [21], and demonstrated a better progression-free survival outcome with lower toxicities [22].
In a randomised Phase II clinical trial, patients with ipilimumab and targeted therapy (if BRAF mutant) refractory advanced melanoma had improved progression-free survival when treated with pembrolizumab compared with investigators choice of cytotoxic chemotherapy with a likelihood of 6-month progression-free survival of 34% versus 16%. Serious treatment-related adverse events were far less common with immunotherapy – 11% versus 26% with chemotherapy. The likelihood of radiologic response was 5 times higher with pembrolizumab (21%) than chemotherapy (4%) [23].
Selection of patients who are most likely to benefit from immune checkpoint blockade remains largely an elusive goal, although potential biomarkers are emerging and these include a high somatic mutational burden with resultant abundant neo-epitopes for immune recognition [24], a greater diversity within the faecal microbiome and the presence therein of specific bacterial species [25], the level of PD-L1 expression on tumour cells and tumour-associated leukocytes [26] and density of CD8 T-cell tumoural infiltrate [27]. Identification of predictive biomarkers for immunotherapy would allow futile treatment and associated toxicities to be avoided in patients unlikely to benefit.
Ipilimumab was the first checkpoint inhibitor to be used in patients with CNS metastases. In 2012, Margolin et al. published a phase 2 study involving 72 melanoma patients with CNS metastases who received intravenous ipilimumab. Intra-cranial disease control (defined as objective response or stable disease for at least 3 months) was achieved in 24% of the patients who were asymptomatic and not receiving corticosteroids and 10% in those with symptomatic, steroid-requiring lesions [28]. However, in a real-world study of ipilimumab for metastatic melanoma patients in the UK, median overall survival for those with brain metastases was 3.5 months [16]. This was followed by another open-label phase 2 trial using intravenous Pembrolizumab [29]. Of 18 patients enrolled into that study, 22% achieved disease control intracranially. Recently, Tawbi et al. published in the New England Journal of Medicine a larger trial involving 94 patients being treated with combination immunotherapy [30]. In patients with small (less than 3 cm) asymptomatic brain metastases, the intracranial clinical benefit rate (objective response or stable disease for at least 6 months) was 57%, there were also higher chances of grade 3 and 4 toxicities (55%). The rate of radiologic complete response within the brain is notable at 26% and this may be a surrogate marker of long-term survival. Intra-cranial responses were achieved rapidly with a median time to response of 2.3 months. The rate of intra-cranial response was in fact slightly numerically higher than that of extra-cranial metastases. Similar findings were noted in Long’s study including patients with lesion size up to 40 mm with an intra-cranial response rate of 46% (in pre-treated patients) and 56% in systemic-therapy naïve patients and 53% of patients were free of intra-cranial progression at 6 months, using ipilimumab and nivolumab. However, combination immunotherapy was of marginal benefit in patients with progression after prior local treatment for brain metastases, neurologic symptoms or lepto-meningeal disease with a single partial intra-cranial response amongst 16 patients, only 13% were free of intra-cranial progression at 6 months and median overall survival was poor at 5.1 months (similar to that of historic patients treated with supportive care with or without whole brain radiotherapy) [31]. Ipilimumab monotherapy, even at doses as high as 10 mg/kg with associated toxicities, was also ineffective in patients with neurologic symptoms with an intra-cranial response rate of 5% and median overall survival of 3.7 months as described by Margolin et al. [28] Anti PD-1 monotherapy appears to be a valid treatment option with intra-cranial response rates of 22–26% and median overall survival of 18 months [32]. However, the durability of responses when patients have brain metastases remains uncertain, and by way of comparison, median overall survival for patients without brain metastases treated with pembrolizumab was 24 months and 38.6 months in treatment-naive patients [33].
When taken as a whole, most clinical trials of immunotherapy appear to show potential clinical benefit to melanoma patients with CNS metastases, with combination immunotherapy possibly providing the best clinical outcomes but at the cost of higher toxicity.
Approximately 45 to 50% of patients with metastatic cutaneous melanoma harbour missense mutations involving the BRAF proto-oncogene (codon 600) and in these patients MAP kinase targeted therapies such dabrafenib with trametinib or encorafenib with binimetinib are a valid treatment option with high rates of radiologic response including intra-cranial responses. There is no randomised clinical trial evidence to guide the selection of 1st line systemic therapy in BRAF mutant patients, concurrent treatment with MAP kinase inhibitors and immune checkpoint inhibitors remains a highly experimental approach albeit with some early signals that combination treatment can be safely delivered and there is no clinically useful predictive biomarker for immunotherapy benefit. This remains a nuanced clinical dilemma for the oncologist and patient. RAF and MEK inhibitors have direct anti-proliferative effects on the melanoma cells and do not rely on using the immune system as an effector and their effectiveness is not blunted by immunosuppressive therapies such as corticosteroids. Therefore, many patients with melanoma brain metastasis have received targeted therapy in the first line setting with rapid tumour control and neurological improvement in the majority but durability of response is limited with typical intra-cranial progression free survival of 6–8 months. Rapid progression of metastatic disease, and particularly CNS metastases, when refractoriness to RAF and MEK inhibitors inevitably develops often leads to a sharp decline in performance status and many patients are unable to receive or benefit from immunotherapeutic approaches in the second line setting. In fact, an Australian retrospective study found that only 35% of patients discontinuing front-line targeted therapy for progressive disease went on to receive subsequent lines of systemic therapy [34]. There is also biological evidence that the increased melanoma differentiation antigen expression, enhanced dendritic cell function and increased CD8 T-cell infiltration driven by RAF–MEK inhibitors early on in treatment (2 weeks) is lost at the time of tumour progression, creating an ‘immune desert’ environmental that is hostile to the effects of immune checkpoint inhibitors. Therefore, where small asymptomatic brain metastases are present or when brain lesions have been treated with ablative radiotherapy, immunotherapy should be the preferred initial treatment.
Radiotherapy is widely used to treat intracranial melanoma, i.e., brain metastasis, in order to control disease, alleviate symptoms and even improve survival. The two main forms of radiotherapy are stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT). Radiotherapy planning, dose and schedule, and outcomes differs between SRS and WBRT.
As the name implies WBRT involves the irradiation of the entire intracranial contents, tumour and normal brain tissue alike. WBRT is often used when intracranial disease is extensive, such as large and/or multiple brain metastasis or leptomeningeal disease, and when radical treatment is not possible. Even with WBRT, overall survival is poor in the order of 6 months and patients are unlikely to survive long enough to develop late toxicity of irradiation of normal brain such as neurocognitive impairment. Treatment set up typically involves a pair of opposing photon beams, from the patients left and right, which converge in the mid-plane to deliver dose throughout the cranium. 20Gy in five daily fractions and 30Gy in ten fractions over two weeks are two commonly used conventional WBRT schedules worldwide with the latter the standard schedule in the United Kingdom [35]. Clinical trials did not demonstrate any benefit in improvement of neurological function or overall survival with dose escalation over conventional WBRT [36]. Despite widespread use worldwide over decades, only two clinical trials compared WBRT with best supportive care. The first, published in 1971, reported no difference in survival between WBRT and oral prednisolone alone but the study was conducted in the pre computed tomography era and hampered by a small cohort and inadequate statistics [37]. The QUARTZ trial reported in 2016 is a multi-centred, statistically powered trial conducted on patients with non-small cell lung cancer (NSCLC) with brain metastases unsuitable for radical treatment. There was no significant difference in overall survival and quality of life between patients treated with WBRT compared to dexamethasone and best supportive care alone. Overall survival was in the order of 9 weeks which is a reflection of poor prognosis with brain metastases and the limited effect of WBRT. Subgroup analysis indicated that patients under 60 or with five of more brain metastases might derive a survival benefit from WBRT [38]. Although this trial was limited to NSCLC, it is likely that similar results will be observed with WBRT to brain metastases from other cancer types. WBRT is no longer default option in managing brain metastases unsuitable for radical treatment given the lack of clear benefit in survival or quality of life, potential toxicity and inconvenience to the patient. Instead, the clinician should consider patient factors, such as age, performance status, systemic disease status and patient wishes, in tailoring a patient-centred management plan which includes best supportive care.
Patients with limited brain metastases such as solitary or oligometastatic metastases or small volume disease, could benefit from treatment such as neurosurgery and SRS which are more targeted and radical than WBRT. These treatment modalities can achieve superior long-term control compared to WBRT. For instance, local control rate after SRS is in the order of 70–90% at 1 year [3, 39, 40, 41, 42]. Decision to treat with SRS or neurosurgery should be made in a multi-disciplinary setting. A brain metastasis that is solitary, accessible, or large volume causing pressure symptoms is an ideal candidate for neurosurgery whereas lesions that are small in volume, surgically inaccessible or multiple are suitable for SRS. Patient factors such as surgical and anaesthetic risk and comorbidities need to be taken into account too [43]. Outcomes after neurosurgery and SRS are similar; a meta-analysis reported non-significant difference in local control between SRS and neurosurgery at 1 year, and non-significant difference in overall survival at 1 and 2 years [44].
Unlike WBRT, SRS is focused high dose radiotherapy on the brain metastases with steep dose fall off to reduce irradiation of normal brain. Multiple brain metastases up to a total of 20 ml can be treated. The volume limit is intended to limit collateral dose to normal brain. Treatment set up involves the patients being immobilised either with a stereotactic frame or custom-made thermoplastic mask which serve to minimise movement and error during treatment delivery. Small lesions such as those under 2 cm can be treated with 20 Gy in a single fraction while larger lesions or those close to critical structures such as the brain stem or optic chiasm are treated with lower dose of 15–18 Gy in a single fraction or a fractionated schedule such as 27Gy in three fractions. Acute toxicities of SRS include headache, nausea, fatigue and risk of seizure and are often self-limiting and managed with steroids.
The addition of WBRT to SRS reduces the risk of intracranial recurrence but this does not translate into a survival benefit [3, 42, 45]. Intracranial recurrence, either with local recurrence of previously treated lesion or distant recurrence of new lesions, can potentially be treated with repeat SRS which obviates the need for upfront WBRT. WBRT also increases the risk of late neurotoxicity such as leukoencephalopathy and neurocognitive impairment which can manifest many months after treatment and result in significant detriment in quality of life and function [42, 45, 46]. Late neurotoxicity is a significant concern especially for patients who will otherwise have long term systemic disease control, such as patients with melanoma with good response to immunotherapy. The addition of WBRT to SRS is therefore not the standard of care in the United Kingdom. Instead, radiological surveillance with MRI to detect recurrence is performed after SRS [10].
Radiotherapy can disrupt the blood–brain barrier allowing the entry of drugs into the central nervous system circulation. Concurrent radiotherapy and immunotherapy might have a synergistic effect stimulating the immune response resulting in greater anti-cancer effect. Several retrospective studies have reported excellent outcomes with concurrent radiotherapy and immunotherapy for melanoma. One study on reported overall survival of 56 months with SRS and immunotherapy compared to 24 months and 14 months with immunotherapy alone and SRS alone respectively, while another study reported significantly longer overall survival (15.9 months vs. 6.1 months) and lower cumulative incidence of neurologic death (9% vs. 23%) with SRS and immunotherapy compared to SRS alone [47, 48]. The synergistic effect of radiotherapy and immunotherapy on the immune response in theory could result in more severe acute toxicity, however these studies also report good safety profile with low incidences of grade III or greater toxicity. Treatment scheduling and long-term outcomes and toxicities of combined immunotherapy and radiotherapy are areas of ongoing research interest.
The landscape of systemic treatments of MBM patients has undergone tremendous evolution over the past decades and there has been major improvement in outcome for this disease.
Immunotherapy is a relatively safe option for MBM patients with anti-PD-1 having least toxicity and associated with no reported treatment related death. On the other hand, Ipilimumab is associated with increase in immune related toxicities but Ipilimumab and Nivolumab has shown increase in overall survival when comparing with monotherapy. Also, combination with radiotherapy and immunotherapy provides a higher response rate but potential increase in CNS toxicities. More studies are needed to determine the progression free survival, patient’s satisfaction and quality of life as well as assessing the cost effectiveness of the treatments.
Combination of immunotherapy with cytotoxic chemotherapy or targeted therapy may also be a potential therapeutic approach, but further understanding of drug mechanism is required.
Special thanks to Professor Poulam Patel and Dr. Ankit Rao for their ongoing encouragement and guidance.
The authors declare no conflict of interest.
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\n\nWe have adopted the Protocol to increase the number of readers of our publications. All our Works are more widely accessible, with resulting benefits for scholars, researchers, students, libraries, universities and other academic institutions. Through this method of exposing metadata, IntechOpen enables citation indexes, scientific search engines, scholarly databases, and scientific literature collections to gather metadata from our repository and make our publications available to a broader academic audience.
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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. 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De",surname:"Nazaré",slug:"fabio-nazare",fullName:"Fábio Nazaré"}]},{id:"15098",doi:"10.5772/15736",title:"Silicon Carbide: Synthesis and Properties",slug:"silicon-carbide-synthesis-and-properties",totalDownloads:23099,totalCrossrefCites:29,totalDimensionsCites:68,abstract:null,book:{id:"83",slug:"properties-and-applications-of-silicon-carbide",title:"Properties and Applications of Silicon Carbide",fullTitle:"Properties and Applications of Silicon Carbide"},signatures:"Houyem Abderrazak and Emna Selmane Bel Hadj Hmida",authors:[{id:"18643",title:"Dr.",name:"Houyem",middleName:null,surname:"Abderrazak",slug:"houyem-abderrazak",fullName:"Houyem Abderrazak"},{id:"23082",title:"Dr.",name:"Emna Selmane",middleName:null,surname:"Bel Hadj Hmida",slug:"emna-selmane-bel-hadj-hmida",fullName:"Emna Selmane Bel Hadj Hmida"}]},{id:"47585",doi:"10.5772/58884",title:"Free Space Optical Communications — Theory and Practices",slug:"free-space-optical-communications-theory-and-practices",totalDownloads:9078,totalCrossrefCites:45,totalDimensionsCites:64,abstract:null,book:{id:"4473",slug:"contemporary-issues-in-wireless-communications",title:"Contemporary Issues in Wireless Communications",fullTitle:"Contemporary Issues in Wireless Communications"},signatures:"Abdulsalam Ghalib Alkholidi and Khaleel Saeed Altowij",authors:[{id:"100466",title:"Dr.",name:"Abdulsalam",middleName:null,surname:"Alkholidi",slug:"abdulsalam-alkholidi",fullName:"Abdulsalam Alkholidi"},{id:"131091",title:"MSc.",name:"Khalil",middleName:null,surname:"Altowij",slug:"khalil-altowij",fullName:"Khalil Altowij"}]}],mostDownloadedChaptersLast30Days:[{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1264,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",book:{id:"8899",slug:"modelling-and-control-of-switched-reluctance-machines",title:"Modelling and Control of Switched Reluctance Machines",fullTitle:"Modelling and Control of Switched Reluctance Machines"},signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",middleName:null,surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",middleName:null,surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",middleName:null,surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",middleName:null,surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}]},{id:"52822",title:"Non-Orthogonal Multiple Access (NOMA) for 5G Networks",slug:"non-orthogonal-multiple-access-noma-for-5g-networks",totalDownloads:14893,totalCrossrefCites:31,totalDimensionsCites:40,abstract:"In this chapter, we explore the concept of non-orthogonal multiple access (NOMA) scheme for the future radio access for 5G. We first provide the fundamentals of the technique for both downlink and uplink channels and then discuss optimizing the network capacity under fairness constraints. We further discuss the impacts of imperfect receivers on the performance of NOMA networks. Finally, we discuss the spectral efficiency (SE) of the networks that employ NOMA with its relations with energy efficiency (EE). We demonstrate that the networks with NOMA outperform other multiple access schemes in terms of sum capacity, EE and SE.",book:{id:"5480",slug:"towards-5g-wireless-networks-a-physical-layer-perspective",title:"Towards 5G Wireless Networks",fullTitle:"Towards 5G Wireless Networks - A Physical Layer Perspective"},signatures:"Refik Caglar Kizilirmak",authors:[{id:"188668",title:"Dr.",name:"Refik Caglar",middleName:null,surname:"Kizilirmak",slug:"refik-caglar-kizilirmak",fullName:"Refik Caglar Kizilirmak"}]},{id:"77871",title:"Protection of Microgrids",slug:"protection-of-microgrids",totalDownloads:301,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The concept of microgrids goes back to the early years of the electricity industry although the systems then were not formally called microgrids. Today, two types of microgrids can be seen: independent and grid connected. The protection requirement of these two types differs as the protection needs of an independent microgrid are intended for protecting components and systems within the microgrid, whereas a grid connected microgrid demands both internal and external protection. The first part of this chapter is dedicated to independent microgrids. How protection devices such as residual current circuit breakers, miniature and moulded case circuit breakers, and surge protective devices should be selected for an example microgrid is discussed while referring to the relevant standards. In the next section, the protection of a grid connected microgrid is discussed. Particularly, micro-source protection, microgrid protection, loss of mains protection and fault ride-through requirements are discussed while referring to two commonly used distributed generator connection codes. An example with simulations carried out in the IPSA simulation platform was used to explain different protection requirements and calculation procedures. Finally, grounding requirements are discussed while referring to different interfacing transformer connections and voltage source inverter connections.",book:{id:"10176",slug:"microgrids-and-local-energy-systems",title:"Microgrids and Local Energy Systems",fullTitle:"Microgrids and Local Energy Systems"},signatures:"Janaka Ekanayake",authors:[{id:"328170",title:"Prof.",name:"Janake",middleName:null,surname:"Ekanayake",slug:"janake-ekanayake",fullName:"Janake Ekanayake"}]},{id:"47585",title:"Free Space Optical Communications — Theory and Practices",slug:"free-space-optical-communications-theory-and-practices",totalDownloads:9076,totalCrossrefCites:45,totalDimensionsCites:64,abstract:null,book:{id:"4473",slug:"contemporary-issues-in-wireless-communications",title:"Contemporary Issues in Wireless Communications",fullTitle:"Contemporary Issues in Wireless Communications"},signatures:"Abdulsalam Ghalib Alkholidi and Khaleel Saeed Altowij",authors:[{id:"100466",title:"Dr.",name:"Abdulsalam",middleName:null,surname:"Alkholidi",slug:"abdulsalam-alkholidi",fullName:"Abdulsalam Alkholidi"},{id:"131091",title:"MSc.",name:"Khalil",middleName:null,surname:"Altowij",slug:"khalil-altowij",fullName:"Khalil Altowij"}]},{id:"41657",title:"Algorithms for Efficient Computation of Convolution",slug:"algorithms-for-efficient-computation-of-convolution",totalDownloads:10220,totalCrossrefCites:15,totalDimensionsCites:20,abstract:null,book:{id:"3158",slug:"design-and-architectures-for-digital-signal-processing",title:"Design and Architectures for Digital Signal Processing",fullTitle:"Design and Architectures for Digital Signal Processing"},signatures:"Karas Pavel and Svoboda David",authors:[{id:"154795",title:"Ph.D. Student",name:"Pavel",middleName:null,surname:"Karas",slug:"pavel-karas",fullName:"Pavel Karas"},{id:"155141",title:"Dr.",name:"David",middleName:null,surname:"Svoboda",slug:"david-svoboda",fullName:"David Svoboda"}]}],onlineFirstChaptersFilter:{topicId:"116",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82123",title:"Microwave-Assisted Pyrolysis Process: From a Laboratory Scale to an Industrial Plant",slug:"microwave-assisted-pyrolysis-process-from-a-laboratory-scale-to-an-industrial-plant",totalDownloads:36,totalDimensionsCites:0,doi:"10.5772/intechopen.104925",abstract:"One of the great challenges for the European Union (EU) is the “Circular Economy Package,” and to achieve this goal, materials at the end of their life cycle must be recycled using a sustainable process. In this way, as a thermochemical treatment, pyrolysis represents a significant opportunity so long it leads to the recovery of both energy and chemical content of mixed, contaminated, or deteriorated plastics. An excellent history of an academic-industrial adventure started in 2008 at the Department of Chemistry of the University of Florence demonstrates the possibility of employing microwaves to recycle plastics to preserve their energy and chemical content. After that, Techwave started industrialization of the process in 2019, realizing a small-scale prototype followed by a full-scale pilot plant using different plastic materials (e.g., polystyrene, acrylonitrile-butadiene-styrene (ABS), and polypropylene). Nowadays, the plant may process 90 kg/h of plastics with a low formation of char and gas and an interesting amount of liquid useful as a source of chemicals or fuel because it has an LHV of 35–43 kJ/kg. The Microwave-Assisted Pyrolysis (MAP) is an industrial novelty in plastic recycling, and it looks very promising for a much more modern and innovative plastic waste recovery system.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Marco Frediani, Piero Frediani, Gianni Innocenti, Irene Mellone, Roberto Simoni and Gianpaolo Oteri"},{id:"82420",title:"Applications of Microwaves in Medicine and Biology",slug:"applications-of-microwaves-in-medicine-and-biology",totalDownloads:23,totalDimensionsCites:0,doi:"10.5772/intechopen.105492",abstract:"This chapter deals with the description of recent research activities oriented on the perspective of microwave technologies in medicine and biology. It brings new ideas about the possibilities of using microwaves in thermotherapy—above all toward hyperthermia in cancer treatment. Development of new types of hyperthermia applicators (based, e.g., on technologies such as metamaterials, evanescent modes in waveguides, and other types of transmission structures) will be discussed here. Furthermore, we would like to underline in this chapter perspectives of microwaves in medical diagnostics. It is possible to expect that, e.g., microwave differential tomography, UWB radar, and microwave radiometers (all three can be used both for medical diagnostic and for noninvasive temperature measurement) will soon play an important role in it. Finally, experimental equipment necessary for research on the biological effects of EM fields is presented.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"David Vrba, Jan Vrba, Ondrej Fiser, Jesus Cumana, Milan Babak and Jan Vrba Senior"},{id:"81917",title:"Fluidics for Reconfigurable Microwave Components",slug:"fluidics-for-reconfigurable-microwave-components",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.104857",abstract:"Dielectric and conducting liquids with varying electromagnetic properties can offer novel alternatives for building tunable microwave passive components as well as antennas. Injecting these fluidics in or around microwave substrates alters their overall electrical characteristics, enabling circuit reconfigurability. Alternatively, changing the shapes and dimensions of conductors by using liquid metals can achieve similar reconfigurability. An overview of different liquids and their electromagnetic properties is first given. The principles behind the reconfigurability of the electrical characteristics of typical guiding structures based on mode shape variation in the presence of fluids are discussed. The realization of an N-bit programmable impedance tuner in 3D LTCC technology based on these principles is presented.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Dorra Bahloul, Ines Amor and Ammar Kouki"},{id:"82105",title:"Vehicle-To-Anything: The Trend of Internet of Vehicles in Future Smart Cities",slug:"vehicle-to-anything-the-trend-of-internet-of-vehicles-in-future-smart-cities",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.105043",abstract:"This chapter includes five parts—the concept of vehicle-to-anything (V2X), introduction of visible light communication (VLC), free-space optical communication (FSO), and terahertz (THz). The first part will present the concept of V2X. V2X is the basis and fundamental technology of future smart cars, autonomous driving, and smart transportation systems. Vehicle-to-network (V2N), vehicle-to-vehicle (V2V), vehicle-to-infrastructure (V2I), and vehicle-to-people (V2P) are included in V2X. V2X will lead to a high degree of interconnection of vehicles. The concept of VLC is presented in the second part. Intelligent reflecting surface (IRS) for nano-optics and FSO communication is introduced in the third part. At the same time, IRS keeps pace with the phase in communication links. Prospects of THz in glamorous cities are introduced in the fourth part. These new technologies will lead to trends in the future. A comparison of optical communication technology and applications in V2X is described in the fifth part.",book:{id:"10963",title:"Intelligent Electronics and Circuits - Terahertz, ITS, and Beyond",coverURL:"https://cdn.intechopen.com/books/images_new/10963.jpg"},signatures:"Mingbo Niu, Xiaoqiong Huang and Hucheng Wang"},{id:"82046",title:"One Model of Microwave Heating of Water Drop",slug:"one-model-of-microwave-heating-of-water-drop",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.104949",abstract:"This work deals with the modeling of microwave heating of a water drop. A drop model is reduced to its electric dipoles, masses, and charges are constructed using the associating of COMSOL Multiphysics and Matlab software. The considered model proposes a microscopic point of view on microwave heating, which transforms electrical energy into heat.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Serge Lefeuvre and Olga Gomonova"},{id:"82076",title:"Power Divider/Combiner",slug:"power-divider-combiner",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.104911",abstract:"With the remarkable progress in the use of Internet of Things (IoT) and 5G, there is a demand for higher performance such as miniaturization, broadband/multiband, low loss, and high integration for several microwave circuits. This chapter treats microwave power dividers/combiners used in amplifiers, mixers, phase shifters, antenna feeding networks, and so on. Here, the treated circuits are composed of LC-ladder circuits and an absorption resistor. It shows that multiband (dual-band and tri-band) and broadband can be achieved by changing the number of stages of the LC-ladder circuit. In addition, the effectiveness of this design method is demonstrated by electromagnetic simulations and prototype experiments.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Tadashi Kawai, Ayumu Tsuchiya and Akira Enokihara"}],onlineFirstChaptersTotal:41},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:{name:"Kobe College",institutionURL:null,country:{name:"Japan"}}}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. 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He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. 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Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. 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He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"2",type:"subseries",title:"Prosthodontics and Implant Dentistry",keywords:"Osseointegration, Hard Tissue, Peri-implant Soft Tissue, Restorative Materials, Prosthesis Design, Prosthesis, Patient Satisfaction, Rehabilitation",scope:"