Human telomere shortening associated genes, their functions and mode of inheritance in dyskeratosis congenita [37].
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5496",leadTitle:null,fullTitle:"Fault Diagnosis and Detection",title:"Fault Diagnosis and Detection",subtitle:null,reviewType:"peer-reviewed",abstract:"Mass production companies have become obliged to reduce their production costs and sell more products with lower profit margins in order to survive in competitive market conditions. The complexity and automation level of machinery are continuously growing. This development calls for some of the most critical issues that are reliability and dependability of automatic systems. In the future, machines will be monitored remotely, and computer-aided techniques will be employed to detect faults in the future, and also there will be unmanned factories where machines and systems communicate to each other, detect their own faults, and can remotely intercept their faults. The pioneer studies of such systems are fault diagnosis studies. Thus, we hope that this book will contribute to the literature in this regard.",isbn:"978-953-51-3204-2",printIsbn:"978-953-51-3203-5",pdfIsbn:"978-953-51-4822-7",doi:"10.5772/63169",price:139,priceEur:155,priceUsd:179,slug:"fault-diagnosis-and-detection",numberOfPages:336,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"9d27af6f557a4c54b28af7072dc3fcb6",bookSignature:"Mustafa Demetgul and Muhammet Ünal",publishedDate:"May 31st 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5496.jpg",numberOfDownloads:22019,numberOfWosCitations:34,numberOfCrossrefCitations:35,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:57,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:126,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 28th 2016",dateEndSecondStepPublish:"May 19th 2016",dateEndThirdStepPublish:"August 23rd 2016",dateEndFourthStepPublish:"November 21st 2016",dateEndFifthStepPublish:"December 21st 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"19106",title:"Dr.",name:"Mustafa",middleName:null,surname:"Demetgul",slug:"mustafa-demetgul",fullName:"Mustafa Demetgul",profilePictureURL:"https://mts.intechopen.com/storage/users/19106/images/5677_n.jpg",biography:"Mustafa Demetgul was born in Duzce, Turkey, in 1978. He received the BSc degree, MS degree, and PhD degree in Mechanical Engineering from Marmara University, Istanbul, Turkey. From 2007 to 2009, he was a postdoc with the Mechanical Engineering Department, Florida International University, Florida, USA. Here he has been involved in research on structural health monitoring and energy harvesting. He currently works at the Department of Mechatronics Engineering, Marmara University, as an Assoc. Prof. Dr. His research interests are fault diagnosis, energy harvesting, intelligent materials, automation systems, structural health monitoring, and artificial intelligence systems. He is the director of Fault Diagnosis and Structural Health Monitoring Lab in Marmara University. He is an editorial board member at many international journals. He has publications in many international journals and symposiums on failure diagnosis and fault detection.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"193819",title:"Dr.",name:"Muhammet",middleName:null,surname:"Ünal",slug:"muhammet-unal",fullName:"Muhammet Ünal",profilePictureURL:"https://mts.intechopen.com/storage/users/193819/images/5678_n.jpg",biography:"Dr. Muhammet Ünal works as an assistant professor in the Department of Mechatronics Engineering, Marmara University, Istanbul (Turkey). His research interests are system identification, parameter optimization, real-time control, and structural health monitoring. His primary research interests are vibration analysis and fault diagnosis of mechanical systems. Dr. Ünal has written several papers in vrious fields of mechatronics engineering and one book on control engineering.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"717",title:"Control Theory",slug:"engineering-control-engineering-control-theory"}],chapters:[{id:"54861",title:"Fault Detection and Isolation",doi:"10.5772/67870",slug:"fault-detection-and-isolation",totalDownloads:1885,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Fault diagnosis of a class of linear multiple‐input and multiple‐output (MIMO) systems is developed here. An emulator‐based scheme is proposed to detect and isolate faults in a system formed by interconnected subsystems. Emulators, which are hardware or software devices, are connected to the input and measurement outputs in cascade with the subsystems whose faults are to be diagnosed. The role of an emulator is to induce variations in cascade combination of the nominal fault‐free subsystem so as to mimic the actual perturbations that may occur in the subsystem during the offline identification phase. The emulator‐generated data are employed in the reliable identification of the nominal system, the associated Kalman filter, and a map that relates the emulator parameters to the feature vector. In the operational stage, the Kalman filter residual is used to detect a fault in the system; the emulator parameter that has varied is estimated, and using the emulator‐feature vector map, the faulty subsystem is isolated. The main contributions of this work are accurate and reliable identification of the system, the fault diagnosis of multivariable systems using feature vector-emulator map fault diagnosis of multivariable systems, and the establishment of the key properties of the Kalman filter for fault detection. The proposed scheme was successfully evaluated on a number of simulated as well as physical systems.",signatures:"Rajamani Doraiswami and Lahouari Cheded",downloadPdfUrl:"/chapter/pdf-download/54861",previewPdfUrl:"/chapter/pdf-preview/54861",authors:[{id:"28398",title:"Prof.",name:"Rajamani",surname:"Doraiswami",slug:"rajamani-doraiswami",fullName:"Rajamani Doraiswami"},{id:"37808",title:"Prof.",name:"Lahouari",surname:"Cheded",slug:"lahouari-cheded",fullName:"Lahouari Cheded"}],corrections:null},{id:"54590",title:"Adaptive Signal Decomposition Methods for Vibration Signals of Rotating Machinery",doi:"10.5772/67530",slug:"adaptive-signal-decomposition-methods-for-vibration-signals-of-rotating-machinery",totalDownloads:1860,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Vibration‐based condition monitoring and fault diagnosis are becoming more common in the industry to increase machine availability and reliability. Considerable research efforts have recently been directed towards the development of adaptive signal processing methods for fault diagnosis. Two adaptive signal decomposition methods, i.e. the empirical mode decomposition (EMD) and the local mean decomposition (LMD), are widely used. This chapter is intended to summarize the recent developments mostly based on the authors’ works. It aims to provide a valuable reference for readers on the processing and analysis of vibration signals collected from rotating machinery.",signatures:"Wei Guo and Ming J. Zuo",downloadPdfUrl:"/chapter/pdf-download/54590",previewPdfUrl:"/chapter/pdf-preview/54590",authors:[{id:"191997",title:"Dr.",name:"Wei",surname:"Guo",slug:"wei-guo",fullName:"Wei Guo"},{id:"192000",title:"Prof.",name:"Ming J.",surname:"Zuo",slug:"ming-j.-zuo",fullName:"Ming J. Zuo"},{id:"192189",title:"Dr.",name:"Wenhua",surname:"Chen",slug:"wenhua-chen",fullName:"Wenhua Chen"}],corrections:null},{id:"53779",title:"Enhanced Principles in Design of Adaptive Fault Observers",doi:"10.5772/67133",slug:"enhanced-principles-in-design-of-adaptive-fault-observers",totalDownloads:1331,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, modified techniques for fault estimation in linear dynamic systems are proposed, which give the possibility to simultaneously estimate the system state as well as slowly varying faults. Using the continuous-time adaptive observer form, the considered faults are assumed to be additive, thereby the principles can be applied for a broader class of fault signals. Enhanced algorithms using H∞ approach are provided to verify stability of the observers, giving algorithms with improved performance of fault estimation. Exploiting the procedure for transforming the model with additive faults into an extended form, the proposed technique allows to obtain fault estimates that can be used for fault compensation in the fault tolerant control scheme. Analyzing the ambit of performances given on the mixed H2/H∞ design of the fault tolerant control, the joint design conditions are formulated as a minimization problem subject to convex constraints expressed by a system of linear matrix inequalities. Applied enhanced design conditions increase estimation rapidity also in noise environment and formulate a general framework for fault estimation using augmented or adaptive observer structures and active fault tolerant control in linear dynamic systems.",signatures:"Dušan Krokavec, Anna Filasová and Pavol Liščinský",downloadPdfUrl:"/chapter/pdf-download/53779",previewPdfUrl:"/chapter/pdf-preview/53779",authors:[{id:"18818",title:"Prof.",name:"Dušan",surname:"Krokavec",slug:"dusan-krokavec",fullName:"Dušan Krokavec"},{id:"22287",title:"Prof.",name:"Anna",surname:"Filasová",slug:"anna-filasova",fullName:"Anna Filasová"},{id:"195026",title:"Dr.",name:"Pavol",surname:"Liscinsky",slug:"pavol-liscinsky",fullName:"Pavol Liscinsky"}],corrections:null},{id:"54865",title:"An Assessment on the Non-Invasive Methods for Condition Monitoring of Induction Motors",doi:"10.5772/67917",slug:"an-assessment-on-the-non-invasive-methods-for-condition-monitoring-of-induction-motors",totalDownloads:2167,totalCrossrefCites:8,totalDimensionsCites:11,hasAltmetrics:0,abstract:"The ability to forecast motor mechanical faults at incipient stages is vital to reducing maintenance costs, operation downtime and safety hazards. This paper synthesized the progress in the research and development in condition monitoring and fault diagnosis of induction motors. The motor condition monitoring techniques are mainly classified into two categories that are invasive and non-invasive techniques. The invasive techniques are very basic, but they have some implementation difficulties and high cost. The non-invasive methods, namely MCSA, PVA and IPA, overcome the disadvantages associated to invasive methods. This book chapter reviews the various non-invasive condition monitoring methods for diagnosis of mechanical faults in induction motor and concludes that the instantaneous power analysis (IPA) and Park vector analysis (PVA) methods are best suitable for the diagnosis of small fault signatures associated to mechanical faults. Recommendations for the future research in these areas are also presented.",signatures:"Muhammad Irfan, Nordin Saad, Rosdiazli Ibrahim, Vijanth S.\nAsirvadam, Abdullah S. Alwadie and Muhammad Aman Sheikh",downloadPdfUrl:"/chapter/pdf-download/54865",previewPdfUrl:"/chapter/pdf-preview/54865",authors:[{id:"9739",title:"Dr.",name:"Nordin",surname:"Saad",slug:"nordin-saad",fullName:"Nordin Saad"},{id:"174671",title:"Dr.",name:"Rosdiazli B. Ibrahim",surname:"Ibrahim",slug:"rosdiazli-b.-ibrahim-ibrahim",fullName:"Rosdiazli B. Ibrahim Ibrahim"},{id:"177286",title:"Dr.",name:"Muhammad",surname:"Irfan",slug:"muhammad-irfan",fullName:"Muhammad Irfan"},{id:"191337",title:"Dr.",name:"Vijanth",surname:"Sagayan",slug:"vijanth-sagayan",fullName:"Vijanth Sagayan"},{id:"192401",title:"Dr.",name:"Muhammad Aman",surname:"Sheikh",slug:"muhammad-aman-sheikh",fullName:"Muhammad Aman Sheikh"},{id:"205830",title:"Prof.",name:"Abdullah",surname:"Alwadie",slug:"abdullah-alwadie",fullName:"Abdullah Alwadie"}],corrections:null},{id:"54322",title:"Evaluation of Novelty Detection Methods for Condition Monitoring applied to an Electromechanical System",doi:"10.5772/67531",slug:"evaluation-of-novelty-detection-methods-for-condition-monitoring-applied-to-an-electromechanical-sys",totalDownloads:1590,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Dealing with industrial applications, the implementation of condition monitoring schemes must overcome a critical limitation, that is, the lack of a priori information about fault patterns of the system under analysis. Indeed, classical diagnosis schemes, in general, outdo the membership probability of a measure in regard to predefined operating scenarios. However, dealing with noncharacterized systems, the knowledge about faulty operating scenarios is limited and, consequently, the diagnosis performance is insufficient. In this context, the novelty detection framework plays an essential role for monitoring systems in which the information about different operating scenarios is initially unavailable or restricted. The novelty detection approach begins with the assumption that only data corresponding to the healthy operation of the system under analysis is available. Thus, the challenge is to detect and learn additional scenarios during the operation of the system in order to complement the information obtained by the diagnosis scheme. This work has two main objectives: first, the presentation of novelty detection as the current trend toward the new paradigm of industrial condition monitoring and, second, the introduction to its applicability by means of analyses of different novelty detection strategies over a real industrial system based on rotatory machinery.",signatures:"Miguel Delgado Prieto, Jesús A. Cariño Corrales, Daniel Zurita\nMillán, Marta Millán Gonzalvez, Juan A. Ortega Redondo and René\nde J. Romero Troncoso",downloadPdfUrl:"/chapter/pdf-download/54322",previewPdfUrl:"/chapter/pdf-preview/54322",authors:[{id:"190434",title:"Dr.",name:"Miguel",surname:"Delgado-Prieto",slug:"miguel-delgado-prieto",fullName:"Miguel Delgado-Prieto"},{id:"194487",title:"MSc.",name:"Jesus A.",surname:"Cariño",slug:"jesus-a.-carino",fullName:"Jesus A. Cariño"},{id:"194935",title:"MSc.",name:"Daniel",surname:"Zurita-Millán",slug:"daniel-zurita-millan",fullName:"Daniel Zurita-Millán"},{id:"194936",title:"MSc.",name:"Marta",surname:"Millán Gonzalvez",slug:"marta-millan-gonzalvez",fullName:"Marta Millán Gonzalvez"},{id:"194937",title:"Dr.",name:"Juan A.",surname:"Ortega Redondo",slug:"juan-a.-ortega-redondo",fullName:"Juan A. Ortega Redondo"},{id:"194938",title:"Dr.",name:"René De J.",surname:"Romero Troncoso",slug:"rene-de-j.-romero-troncoso",fullName:"René De J. Romero Troncoso"}],corrections:null},{id:"54040",title:"Fault Diagnosis and Health Assessment for Rotating Machinery Based on Kernel Density Estimation and Kullback-Leibler Divergence",doi:"10.5772/67360",slug:"fault-diagnosis-and-health-assessment-for-rotating-machinery-based-on-kernel-density-estimation-and-",totalDownloads:1375,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"To avoid severe damages and unexpected shutdowns, fault diagnosis and health assessment of rotating machinery have received considerable attention in recent years. On the other hand, as a great amount of data become acquirable and accessible in industry, data-driven tools have become an emerging research area, acting as a complement to the model-based (or physics-based) fault diagnosis and health assessment methods. In this chapter, based on the kernel density estimation (KDE) and the Kullback-Leibler divergence (KLID), a new data-driven fault diagnosis approach and a new health assessment approach are introduced. By utilizing the KDE, the statistical distribution of selected features can be readily estimated without assuming any parametric family of distributions, whereas the KLID is able to quantify the discrepancy between two probability distributions of selected features. An integrated Kullback-Leibler divergence, which aggregates the KLID of all the selected features, is introduced to discriminate various fault types or health status of rotating machinery. The effectiveness of the proposed approaches is demonstrated through three case studies of fault diagnosis and health assessment of rotating machinery.",signatures:"Yu Liu, Chen-Yao Yan and Fan Zhang",downloadPdfUrl:"/chapter/pdf-download/54040",previewPdfUrl:"/chapter/pdf-preview/54040",authors:[{id:"190539",title:"Dr.",name:"Yu",surname:"Liu",slug:"yu-liu",fullName:"Yu Liu"}],corrections:null},{id:"54206",title:"Dynamics-Based Vibration Signal Modeling for Tooth Fault Diagnosis of Planetary Gearboxes",doi:"10.5772/67529",slug:"dynamics-based-vibration-signal-modeling-for-tooth-fault-diagnosis-of-planetary-gearboxes",totalDownloads:2291,totalCrossrefCites:5,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Vibration analysis has been widely used to diagnose gear tooth fault inside a planetary gearbox. However, the vibration characteristics of a planetary gearbox are very complicated. Inside a planetary gearbox, there are multiple vibration sources as several sun-planet gear pairs, and several ring-planet gear pairs are meshing simultaneously. In addition, due to the rotation of the carrier, distance varies between vibration sources and a transducer installed on the planetary gearbox housing. Dynamics-based vibration signal modeling techniques can simulate the vibration signals of a planetary gearbox and reveal the signal generation mechanism and fault features effectively. However, these techniques are basically in the theoretical development stage. Comprehensive experimental validations are required for their future applications in real systems. This chapter describes the methodologies related to vibration signal modeling of a planetary gear set for gear tooth damage diagnosis. The main contents include gear mesh stiffness evaluation, gear tooth crack modeling, dynamic modeling of a planetary gear set, vibration source modeling, modeling of transmission path effect due to the rotation of the carrier, sensor perceived vibration signal modeling, and vibration signal decomposition techniques. The methods presented in this chapter can help understand the vibration properties of planetary gearboxes and give insights into developing new signal processing methods for gear tooth damage diagnosis.",signatures:"Xihui Liang, Ming J. Zuo and Wenhua Chen",downloadPdfUrl:"/chapter/pdf-download/54206",previewPdfUrl:"/chapter/pdf-preview/54206",authors:[{id:"191577",title:"Dr.",name:"Xihui",surname:"Liang",slug:"xihui-liang",fullName:"Xihui Liang"}],corrections:null},{id:"54144",title:"Fault-Tolerant Electrical Machines and Drives",doi:"10.5772/67354",slug:"fault-tolerant-electrical-machines-and-drives",totalDownloads:1582,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The last years of research and development in the automotive industry were still focused on designing electrical propulsion units to be eco-friendly and diminish the drawbacks of classical combustion engines. Besides being energy efficient, silent, and high in power density, these must have a serious fault-tolerant ability as driver, and passengers’ safety is probably the most important issue in this filed. The chapter will detail fault-tolerant machines and power electronic architectures with their control for the most common ones, such as switched reluctance machines (SRM) and the permanent-magnet synchronous machines (PMSM). Besides detection, solutions will be presented for the machine-drive unit to wisely overcome and compensate occurred faults. A novel modular structure of SRM is presented with increased fault tolerance and possibility of fast repair in case of any machine damage. The solutions will be validated via simulated and experiment-based results.",signatures:"Mircea Ruba",downloadPdfUrl:"/chapter/pdf-download/54144",previewPdfUrl:"/chapter/pdf-preview/54144",authors:[{id:"190371",title:"Dr.",name:"Mircea",surname:"Ruba",slug:"mircea-ruba",fullName:"Mircea Ruba"}],corrections:null},{id:"54834",title:"Fault Detection and Isolation of Nonlinear Systems with Generalized Hamiltonian Representation",doi:"10.5772/68084",slug:"fault-detection-and-isolation-of-nonlinear-systems-with-generalized-hamiltonian-representation",totalDownloads:1356,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The problem of fault diagnosis in a class of nonlinear system is considered. Systems that can be written in the so‐called Generalized Hamiltonian Representation (which is equivalent to an Euler‐Lagrange representation) are studied, and a model‐based observer approach for this class of systems is developed. The main advantage of the proposed approach is the facility to design the required observers, which take advantage of the system structure given by the Hamitonian representation. In order to show the proposed schema, a model of a permanent magnet synchronous machine is revised and the fault diagnosis schema presented. Simulation results confirm the effectivity of the proposed schema.",signatures:"Luis Humberto Rodriguez-Alfaro, Efrain Alcorta-Garcia, Cornelio\nPosadas-Castillo and David Alejandro Diaz-Romero",downloadPdfUrl:"/chapter/pdf-download/54834",previewPdfUrl:"/chapter/pdf-preview/54834",authors:[{id:"191626",title:"Prof.",name:"Efrain",surname:"Alcorta-Garcia",slug:"efrain-alcorta-garcia",fullName:"Efrain Alcorta-Garcia"},{id:"191943",title:"Dr.",name:"Luis Humberto",surname:"Rodriguez Alfaro",slug:"luis-humberto-rodriguez-alfaro",fullName:"Luis Humberto Rodriguez Alfaro"},{id:"191944",title:"Prof.",name:"Cornelio",surname:"Posadas Castillo",slug:"cornelio-posadas-castillo",fullName:"Cornelio Posadas Castillo"},{id:"191946",title:"Prof.",name:"David Alejandro",surname:"Diaz Romero",slug:"david-alejandro-diaz-romero",fullName:"David Alejandro Diaz Romero"}],corrections:null},{id:"54400",title:"Process Monitoring Using Data-Based Fault Detection Techniques: Comparative Studies",doi:"10.5772/67347",slug:"process-monitoring-using-data-based-fault-detection-techniques-comparative-studies",totalDownloads:2097,totalCrossrefCites:16,totalDimensionsCites:28,hasAltmetrics:0,abstract:"Data based monitoring methods are often utilized to carry out fault detection (FD) when process models may not necessarily be available. The partial least square (PLS) and principle component analysis (PCA) are two basic types of multivariate FD methods, however, both of them can only be used to monitor linear processes. Among these extended data based methods, the kernel PCA (KPCA) and kernel PLS (KPLS) are the most well-known and widely adopted. KPCA and KPLS models have several advantages, since, they do not require nonlinear optimization, and only the solution of an eigenvalue problem is required. Also, they provide a better understanding of what kind of nonlinear features are extracted: the number of the principal components (PCs) in a feature space is fixed a priori by selecting the appropriate kernel function. Therefore, the objective of this work is to use KPCA and KPLS techniques to monitor nonlinear data. The improved FD performance of KPCA and KPLS is illustrated through two simulated examples, one using synthetic data and the other using simulated continuously stirred tank reactor (CSTR) data. The results demonstrate that both KPCA and KPLS methods are able to provide better detection compared to the linear versions.",signatures:"Mohammed Ziyan Sheriff, Chiranjivi Botre, Majdi Mansouri, Hazem\nNounou, Mohamed Nounou and Mohammad Nazmul Karim",downloadPdfUrl:"/chapter/pdf-download/54400",previewPdfUrl:"/chapter/pdf-preview/54400",authors:[{id:"21281",title:"Prof.",name:"Hazem",surname:"Nounou",slug:"hazem-nounou",fullName:"Hazem Nounou"},{id:"21282",title:"Prof.",name:"Mohamed N.",surname:"Nounou",slug:"mohamed-n.-nounou",fullName:"Mohamed N. Nounou"},{id:"191340",title:"Mr.",name:"M. Ziyan",surname:"Sheriff",slug:"m.-ziyan-sheriff",fullName:"M. Ziyan Sheriff"},{id:"191341",title:"Mr.",name:"Chiranjivi",surname:"Botre",slug:"chiranjivi-botre",fullName:"Chiranjivi Botre"},{id:"191343",title:"Dr.",name:"Majdi",surname:"Mansouri",slug:"majdi-mansouri",fullName:"Majdi Mansouri"},{id:"191345",title:"Prof.",name:"M. Nazmul",surname:"Karim",slug:"m.-nazmul-karim",fullName:"M. Nazmul Karim"}],corrections:null},{id:"55395",title:"Noninvasive Methods for Condition Monitoring and Electrical Fault Diagnosis of Induction Motors",doi:"10.5772/67245",slug:"noninvasive-methods-for-condition-monitoring-and-electrical-fault-diagnosis-of-induction-motors",totalDownloads:1512,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"This chapter provides a comprehensive analysis of noninvasive methods to diagnose stator winding insulation faults of an induction motor. Further, a novel noninvasive method is proposed to diagnose the root cause of winding failure due to unbalanced voltage to avoid catastrophic failure. Therefore, a winding function approach is utilized to derive an analytical expression for stator winding distribution and magnetomotive force (MMF). This tactic qualifies the conductor segment that generates MMF, and it also helps to analyze a healthy current spectrum. One can easily observe higher order harmonics in current spectrum; therefore, a new series of rotor harmonics is introduced to diagnose unbalanced supply. The locus of these harmonics is dependent on the poles, rotor bars, and slip. Due to the rapid complexity in industrial plants, it is inconceivable to continue human inspection to diagnose the faults. Thus, to avoid human inspection, in addition to new series of rotor harmonic, a fully automatic method based on neural network is proposed. This method not only diagnoses unbalanced voltage but it also recognize the percentage of unbalanced voltage by use of feed-forward multilayer perceptron (MLP) trained by back propagation. Finally, the experimental results shows the validation of this research work proposed method.",signatures:"Muhammad Aman Sheikh, Nursyarizal Mohd Nor, Taib Ibrahim,\nSheikh Tahir Bakhsh, Muhammad Irfan and Hanita Binti Daud",downloadPdfUrl:"/chapter/pdf-download/55395",previewPdfUrl:"/chapter/pdf-preview/55395",authors:[{id:"192401",title:"Dr.",name:"Muhammad Aman",surname:"Sheikh",slug:"muhammad-aman-sheikh",fullName:"Muhammad Aman Sheikh"},{id:"2264",title:"Mr.",name:"Nursyarizal",surname:"Mohd Nor",slug:"nursyarizal-mohd-nor",fullName:"Nursyarizal Mohd Nor"},{id:"193010",title:"Dr.",name:"Taib",surname:"Ibrahim",slug:"taib-ibrahim",fullName:"Taib Ibrahim"}],corrections:null},{id:"54720",title:"Detection and Analysis of Petroleum Equipment Faults",doi:"10.5772/intechopen.68227",slug:"detection-and-analysis-of-petroleum-equipment-faults",totalDownloads:1533,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The method fitness‐for‐service (FFS) provides the means by which the operator of a technical system can decide: It can continue to work safely, reducing of working parameters or stopping the equipment and reparation it. A case study concerning a natural gas pipeline is introduced. 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Shortening",doi:"10.5772/intechopen.88792",slug:"syndromes-associated-with-telomere-shortening",body:'\nOver the years, it has been observed that many degenerative disorders are associated with telomere dysfunction. Telomeres are present at the end of chromosomes. They protect the chromosome ends and critical genetic information in the chromosome from degradation by acting as caps from fusing with other chromosomes [1]. We know that the replication machinery cannot completely copy the chromosome ends, which is called end replication problem. As a result, the telomeres get shorter with each replicative cycle that leads to cell senescence [2]. Short telomeres are associated with genome instability. Telomere dysfunction caused by defects in telomerase proteins is associated with genomic instability that increases genetic mutations characterized by an increased incidence of cancer and also high sensitivity to genotoxic compounds. Short telomeres activate a p53-dependent checkpoint, which leads to senescence and apoptosis of the cells [3, 4, 5, 6]. Telomere shortening can be caused by some external factors also such as smoking, stress, poor health such as obesity, inflammation [7]. Telomere shortening is also accelerated due to chemical and physical environmental agents. Reactive oxygen species can produce modified bases (mainly 8-oxoG) and single strand breaks in the genome. Oxidative damage can result from high incidence of guanine residues in telomeric DNA sequences [8]. Telomere shortening has been recognized as one of the important determinants behind senility and some diseases including—dyskeratosis congenita (DC), idiopathic pulmonary fibrosis (IPF) [9]. Telomere length is maintained by an enzyme called telomerase that adds telomeric repeats to the chromosome 3′-end using an RNA template. The enzyme is a ribonucleoprotein complex, which is inactive in somatic cells but active in stem cells and most cancer cells [10, 11]. Dysfunctional telomeres are recognized by many DNA damage response proteins leading to chromosome fusions, genome instability and altered gene expression patterns [12, 13]. Several cellular processes including apoptosis, aging, carcinogenesis, and chromosome instability are caused as consequences of loss of telomeres [14, 15].
\nHermann J. Muller and Barbara McClintock in the 1930s described the telomere as a protective structure of DNA present at the end of the chromosome [16]. It protects the chromosome structure. The human telomeres have repetitive 5′-TTAGGG-3′ subunits, associated with a variety of telomere-associated proteins. The structure consists of a portion of the double-stranded DNA with an overhanging 3′ G-rich end (Figure 1) [1, 16].
\n3′ overhanging of telomere.
Human somatic cells enter replicative senescence after a limited number of replications. This occurs due to the end replication problem leading to shortening of telomeres [17]. In absence of this structure, the replication cycle stops and the end-to-end fusion of chromosomes may occur [18, 19, 20]. Telomeres are bound by a specialized protein complex called shelterin [21, 22, 23, 24]. Due to the end replication problem, the telomeres shorten with each cell cycle, and these short telomeres induce the DNA damage response and activate the p−53 dependent checkpoint, leading to apoptosis or senescence (Figure 2A) [21]. But in case of germ cells or in cancer cells, telomere maintenance is observed likely due to the expression or reactivation of telomerase, thus the replicative cycle of the cells continue.
\n(A) Telomere shortening leads to DNA damage response. The DNA damage responses include apoptosis, senescence of the cell or genomic instability that can lead to cancer. (B) “Lagging strand” end-replication problem. With each replication cycle the ends of the chromosome get shortened as the final RNA primer at the 3′-end cannot be replaced with DNA. (C) External factors associated with telomere shortening and maintenance.
The telomere shortening takes place as the eukaryotic DNA polymerases have no mechanism for synthesizing the final nucleotides present on the “lagging strand” of the double-stranded DNA. DNA polymerase synthesizes new DNA only from the 5′ → 3′ direction. The two strands of DNA are complementary, one strand is in 5′ → 3′ direction, while the other is in 3′ → 5′. DNA polymerase cannot synthesize DNA in the 3′ → 5′ direction. The process is compensated by the use of Okazaki fragments. Okazaki fragments are short pieces of DNA that are synthesized in the 5′ → 3′ direction from the 3′ → 5′ end as the replication fork moves. As RNA primer is required by DNA polymerase to synthesize new strand, each Okazaki fragment consists of an RNA primer followed by short DNA sequence. When the DNA polymerase reaches the chromosome end, the RNA primer is again placed, which is inevitably removed. But as the primer is removed, the DNA polymerase cannot synthesize the remaining bases leading to telomere shortening with each replicative cycle (Figure 2B) [16, 25, 26].
\nIn addition to that several external factors can also affect telomere length and maintenance. Factors such as smoking, alcohol consumption, chemical and environmental pollutants, radiation and many more can affect telomere length (Figure 2C).
\nThe telomerase enzyme is a ribonucleoprotein containing both RNA and protein. It functions as a reverse transcriptase that positively regulates the telomere length [21, 27, 28]. The ribonucleoprotein has two essential components: telomerase reverse transcriptase (hTERT), the catalytic component, and telomerase RNA component (hTERC or hTR) which provides the template for telomere addition. Telomerase synthesizes new telomeres by solving the end-replication problem (Figure 3) [29].
\nAn image showing how telomerase elongates telomere ends progressively.
Biogenesis of telomerase in somatic cells requires the assembly of hTERT and hTR into a stable complex that can function at telomeres. hTR (RNA component of telomerase) contains a box H/ACA motif which regulates RNA trafficking and stability. This H/ACA motif allows the hTR to associate with the dyskerin complex. This dyskerin complex is a four-protein core of dyskerin protein with another three nucleolar proteins—NOP10, NHP2, and GAR1 (Figure 4) [21, 30, 31]. Mutations in five out of six components that make up the telomerase ribonucleoprotein have been identified in humans causing telomere syndrome. These H/ACA RNAs can be divided into two groups. First, H/ACA small nucleolar RNAs (snoRNAs), that modifies ribosomal RNAs by accumulating in the nucleolus. Second, H/ACA small Cajal body-specific RNAs (scaRNAs) direct the modification of splicing RNAs by accumulating in Cajal bodies [32]. The difference in cellular trafficking between the two groups is attributable to the presence of another sequence motif, called Cajal body box or CAB box. They are the subnuclear sites of ribonucleoprotein assembly and modification [33]. The hTR has both H/ACA motif and also CAB box.
\nThe essential telomerase components.
Shelterin component of telomerase regulates the synthesis of telomeres. It regulates the telomere length by forming t-loops whose formation is controlled by TRF2. TRF2 requires the help of other components such as TRF1 to function. Mutations in the shelterin components such as TRF2 and POT1 are found to be associated with short telomeres leading to such syndromes (Figure 5) [34].
\nThe shelterin complex.
A number of studies have revealed that in normal somatic cells the telomerase activity is almost absent. However a low level of telomerase activity has been found in mitotically active cells, including skin, lymphocytes, and endometrium. Telomerase enzyme is expressed in stem cells to maintain the telomere length all through their life cycle. About 90% of the cancer cells have short telomeres with increased levels of telomerase activity [18]. For example, about 75% cases of oral carcinomas, 80% of lung cancers, 84% of prostate cancers, 85% of liver cancers, 93% of breast cancers, 94% of neuroblastomas, 95% of colorectal cancers, and 98% of bladder cancers have been found to be associated with increased levels of telomerase activity [35].
\nTelomerase transfection in normal cells can lead to the elongation of telomeres. For example, telomerase-negative normal cells, such as retinal pigment epithelial cells and foreskin fibroblasts, transfected with vectors encoding human hTERT show telomere elongation, but telomerase-negative control cells exhibit both telomere shortening and senescence [36].
\nFurthermore, mutations in the telomerase and telomere components lead to the syndromes of telomere shortening (Table 1).
\nHuman telomere shortening associated genes, their functions and mode of inheritance in dyskeratosis congenita [37].
Dyskeratosis congenita (DC) is a rare progressive congenital disorder having a highly variable phenotype [38]. DC is a rare syndrome of premature aging. The term coined by clinicians based on a triad of mucocutaneous features that they found in male children. These are—leukoplakia of the oral mucosa, skin hyperpigmentation, and dystrophy of nails [39]. This triad was associated with premature mortality of children due to bone marrow failure in aplastic anemia. DC mainly affects the skin. But in nearly 80% of the cases, bone marrow failure also occurs. DC is also characterized by the predisposition of cancer. In serious forms, the life span can be significantly shortened.
\nIn 1998, the gene encoding dyskerin, DKC1 was discovered. It was identified in X-linked families with the help of linkage and positional cloning. Dyskerin is a putative box H/ACA telomerase RNA binding protein [40]. The protein links with the telomerase RNA structure. The hTR has a box H/ACA motif and the X-linked DC patients have low levels of telomerase RNA component resulting in short telomeres. It is supported by the fact that mutations in the DKC1 gene disrupt the maturation and stability of hTR. Mutations in the dyskerin complex, NOP1O and NHP2 have also been identified in DC families [41, 42].
\nThe best characterized form of dyskeratosis congenita is a result of one or more mutations in the gene DKC1 present on the long arm of X chromosome. This result in the X-linked recessive form of the disease also called Zinsser-Cole-Engman syndrome wherein the major protein affected is dyskerin [40]. Within the vertebrates, dyskerin is a key component of the telomerase RNA component (hTR) in the form of the H/ACA motif. This X-linked variety, like the NOP10 and NHP2 mutations, demonstrates shortened telomeres as a result of lower hTR concentrations [43, 44].
\nRecently, heterozygous mutations in the shelterin component TINF2 were identified in several cases of DC. Mutations in the TINF2 results in severe manifestations and usually present in children [34, 45]. Different organs show different types of defects in DC patients (Table 2).
\nDefects in DC patients are most often seen in tissues in which cells divide rapidly, and often, many of these cells express telomerase, an enzyme that maintains telomeres.
Many of these cells express telomerase, an enzyme that maintains telomeres.
\nMutations in DKC1 can lead to significant declines in hTR levels, i.e. one fifth of the wild-type [46]. This is consistent with the fact that mutations in the DKC1 lead to accelerated phenotypes because of a loss of greater than half of the available telomerase. Mutations in the shelterin component TINF2 also lead to severe disease. This suggests that telomere defects are alone sufficient to cause dyskeratosis congenita (DC) [40, 42, 43].
\nDue to aplastic anemia when DC patients undergo bone marrow transplant, they frequently suffer with morbidity and mortality from pulmonary fibrosis and liver failure. This happens even when the patients seem to have intact function in these organs during the time of transplant [47, 48]. This happens due to the limited length of the telomeres in the patient’s lung and liver, and also the poor capacity of DNA damage repair after chemotherapy and radiation.
\nNonmyeloablative bone marrow transplant should be considered in aplastic anemia, where there is mutation in the telomere or telomerase components [40].
\nAs many as 10% of the DC patients die due to the cancer diagnosis. DC is thought to be a cancer-prone disorder because of the underlying pathology of abnormal telomere maintenance. The link between DC and cancer is very interesting, because DC is associated with defects in telomere biology. Patients with DC have very short telomeres. Mutations have been identified in telomere biology genes. The United Kingdom Dyskeratosis Congenita Registry (DCR) data indicated that the crude rate of malignancy among approximately 300 patients was 10%. DC patients are at increased risk of myelodysplasia and acute leukemia [49]. Since aplastic anemia itself has an associated increased risk for transformation to acute myeloid leukemia, it is unclear whether DC patients with aplastic anemia have an added predisposition. DC patients also have increased incidence of squamous cell cancers of the skin and head and neck. In DC patients, these cancers are diagnosed at as early as the 2nd decade of the life. DC patients with cancer have a mean age at cancer diagnosis of 29 and a cumulative incidence of ~40% by the age of 50.
\nSusceptibility to cancer seems counterintuitive due to the fact that in many known cancers reactivation of telomerase is actually a required step for malignancy to evolve however short telomeres do contribute to genome instability. In a disease like DC where telomerase is affected, it does not seem that cancer would be a complication to result. But it is discussed that with critically short or absent telomeres, chromosomes will likely be attached together at their ends through the non-homologous end joining pathway (NHEJ). If this occurrence is common enough, then malignancy even without functional telomerase seems probable.
\nFamilies with autosomal dominant dyskeratosis congenita show anticipation and have mutations in the telomerase RNA gene. A null mutation in motif D of the hTERT domain is associated with this phenotype. This mutation leads to haploinsufficiency of telomerase, and telomere shortening occurs despite the presence of telomerase (Figure 6) [50].
\nTelomere shortening despite the presence of telomerase. Mutations in the hTERT or hTR components of telomerase prevent them from extending the telomere length.
This finding shows the importance of telomere maintenance and telomerase dosage for maintaining tissue proliferative capacity. It has also relevance for understanding mechanisms of age-related changes. Telomere length limits the number of replication cycle of primary fibroblasts and has been associated with cellular aging [50]. Short telomeres activate DNA damage response, which leads to apoptosis. It is the shortest telomere and not the average telomere length within a cell that is responsible for mediating the response that leads to cell death [51]. Mutations in the hTERT component can result in a complex phenotype of stem cell failure. This phenotype shows anticipation; it presents earlier and more severely with successive generations. The anticipation is due to haploinsufficiency of telomerase that results in progressive shortening of telomeres (Figure 7) [52]. The hTERT mutation results in haploinsufficiency of telomerase, which leads to shortening of telomeres across generations [49]. The number of these short telomeres is correlated with the severity of phenotypes expressed. The earlier onset of such phenotypes in later generations implicates that in bone marrow and other solid tissues the telomere length is short and in limiting proliferative capacity. This pattern of anticipation suggests that like aplastic anemia, this disorder might also affect the stem cells within the lung.
\nThe figure depicts autosomal dominance mode of inheritance. The dark blue region represents mutant hTERT or hTR allele. Darker shades of black represent progressive telomere shortening leading to anticipation of phenotypes that is the age of onset becomes earlier with each generation.
Aplastic anemia arises when the body’s bone marrow does not make enough new blood cells. It can develop at any age. A number of diseases, conditions and factors can damage the blood-making stem cells in bone marrow and bring about aplastic anemia.
\nAplastic anemia patients with shorter chromosome tips, or telomeres, have a lower survival rate and are much more likely to relapse after treatment than those with longer telomeres. Studies identified germline mutations in the hTR and hTERT components of the telomerase in ~3% of the adults with so-called aplastic anemia [52, 53]. In recent years, scientists have found that some patients suffering with severe aplastic anemia have extremely short telomeres in their blood cells. Telomeres are also known as molecular caps that protect the chromosomes ends from erosion. With each cell division they naturally become shorter, but telomeres can be rebuilt by enzymes. Telomere length is affected by genetic factors and environmental stressors. Patients with short telomeres suffer from morbidity and mortality even after the bone marrow transplant for the aplastic anemia [47, 54]. As these short telomeres lead to organ failures.
\nPatients with the short telomeres are also at greater risk for a conversion to bone marrow cancer (24%).
\nIdiopathic pulmonary fibrosis has a predictable and progressive clinical course that ultimately leads to respiratory failure [55]. Although both genetic and environmental factors have been implicated, the cause of idiopathic pulmonary fibrosis (IPF) is unknown. IPF is the most common manifestation out of the other telomere-mediated disorders [56]. Germ line mutations in the telomerase hTERT and hTR component genes are the reason behind up to one-sixth of pulmonary fibrosis families [57]. The presence of telomerase mutations is significant. As extra-pulmonary complications, affected individuals can suffer from bone marrow failure and cryptogenic liver cirrhosis due to telomere shortening. Evidence suggests that IPF results from autosomal dominant telomere syndromes. Here with successive generations, the condition evolves from pulmonary fibrosis to a disorder of bone marrow failure. It is perhaps the most devastating of the idiopathic disorders in medicine.
\nIPF is an age-related disease. From the time of diagnosis, IPF patients live on average 3 years. Several clinical factors are known which are associated with the IPF. Age is the biggest with the great majority are diagnosed after the age of 60. It is also most frequently in males with a nearly 2:1 ratio [58].
\nDC represents a more severe presentation of a spectrum of telomere syndromes where IPF represents an attenuated form [40]. Pulmonary fibrosis in case of bone-marrow failure can be precipitated by pulmonary toxic drugs during of bone marrow transplant. For example, fatal pulmonary fibrosis in DC patients is caused by the alkylating agent busulfan used in myeloablative conditioning regimens [59]. Even without precipitating toxins, pulmonary fibrosis is a significant and under-estimated complication of DC. In some DC patients, pulmonary fibrosis is the major cause of premature mortality in the absence of bone marrow failure [60].
\nIn most cases, IPF is associated with telomere maintenance. Mutations in hTERT and hTR are the risk factors in 8–15% of familial cases of IPF [57, 61]. In about 3% of sporadic IPF cases, mutations in the telomerase genes are also found [53]. Here hTERT mutations frequency is higher than hTR mutations, but the mutant genes cannot be identified based on only clinical features [62]. Short telomeres are sufficient to cause the common form of IPF [63].
\nThe hTERT and hTR mutations result in short telomeres because of the loss of functions and the haploinsufficiency [56]. As compared to DC and aplastic anemia, the prevalence of IPF is more common, lung disease is the most common manifestation of telomere-mediated disorders [64, 65]. Thus, although DC is specific for identifying individuals with telomere-mediated disease, it only can identify only a small subset, i.e. nearly 5% of all cases.
\nAlthough telomerase mutations are found in one-sixth of the families with IPF, short telomeres are found in other IPF patients without any mutations in the telomerase genes [58]. Significantly shorter telomeres are seen in case of sporadic IPF cases (those who report no family history) [61, 65]. Telomere shortening can be found in immune cells such as lymphocytes, granulocytes and also alveolar epithelial cells, which implicate global telomere defect in such individuals. The observation suggests that individuals with shortest telomeres are more likely to develop IPF than normal individuals in the population [66]. These patients with short telomeres may be a risk factor for disease outside the lung. A subset of sporadic IPF that lack an apparent telomerase mutation also develops cryptogenic liver cirrhosis [57]. There is also relation between IPF and incidence of diabetes. IPF patients have about 3-fold increased incidence of diabetes compared to the age-matched controls [67]. In case of telomerase deficient mice, short telomeres cause defects in insulin secretion resulting in glucose intolerance. Therefore alongside IPF, short telomeres can be a risk factor for diabetes development [68]. Thus in sporadic IPF cases, the defect in telomere length may cause telomere-associated diseases outside of lung.
\nIPF patients and their relatives who carry telomerase mutations can develop telomere-mediated diseases, which are extra-pulmonary [57]. These are, bone-marrow failure including macrocytosis of red blood cells, single lineage cytopenias, aplastic anemia, myelodysplastic syndromes, and acute myeloid leukemia [69, 70, 71]. In case of patients without DC, IPF and bone marrow failure are not considered as related conditions. But occurrence of these two together allows clinical identification of families carrying telomerase mutations. A recent finding suggests that germ line defects in telomerase of a single family are associated with the occurrence of these two disorders together [62]. When present in successive generations, both the IPF and bone marrow failure syndrome together predicted the presence of an hTERT or hTR gene mutation in 10 out of 10 families (100%).
\nOther than the bone marrow failure, IPF patients with telomerase mutations may also develop other complications of telomere-mediated disease like liver cirrhosis [50]. So, the IPF affected individuals are at a higher risk of developing extra-pulmonary diseases.
\nShort telomeres due to mutations in telomerase have been proposed to be associated with cancer. The concept seems counterintuitive as we know that telomerase activation is a required step for malignancy to occur in nearly 85% of the cases as it allows unlimited cell cycle without senescence. How telomerase reactivation occurs in case of cancer is not clear till date. Studies suggest mutations in two key positions of hTERT promoter region (C250T and C228T) cause enhanced expression of hTERT leading to enhanced telomerase activation (Table 3) [72, 73]. But this information needs to be investigated properly. Short telomeres can lead to genomic instability and also cancer via non-homologous end joining (NHEJ) of chromosomes. Mutations in the hTR or hTERT components of telomerase are associated with abnormally short telomeres leading to cancer. Mutations in several components of telomerase such as DKC1, NOP10, NHP2, GAR1 or shelterin components such as TRF1, TRF2, POT1 can lead to short telomeres [30]. Absence or very short telomeres allow non-homologous chromosomes to join head to head. Syndromes associated with short telomeres such as dyskeratosis congenita, aplastic anemia are associated with cancer. It has been found that DC patients are cancer prone. They have increased risk of acute leukemia and myelodysplasia [49]. Aplastic anemia is also associated with acute myeloid leukemia. Patients also have increased risk of squamous cell cancers. Overexpression of TERT is also associated with increased cell proliferation in epidermal tumors and mammary carcinomas in mice [74].
\nTypes of cancers associated with mutations in the telomerase hTERT promoter region.
Thus genomic instability due to loss of telomeres and overexpression of telomerase probably play major roles in such cancer development.
\nCellular aging eventually leads to cell death. It is the progressive decline of cells in resisting stress and other cellular damages. This leads to gradual loss of cellular functions resulting in cell death. Telomere shortening is a major factor that is related with cellular aging. With age, the telomere length declines due to end replication problem, leading to cell senescence. It poses a barrier to the tumor growth but also results in the loss of cells with aging. When the caps of the chromosomes which are telomeres become critically short, it prevents cell cycle to continue leading to either cell senescence or apoptosis. This cell cycle arrest occurs due to DNA damage proteins such as ATM, which become activated when telomere becomes critically shortened leading to activation of p53 dependent checkpoint. Mutations in the telomere or the telomerase components such as hTR or hTERT result in a broad spectrum of diseases present in children and adults. The onset and severity of these diseases are determined by the extent of telomere shortening. Usually the onset of cancer is associated with the activity of the telomerase holoenzyme, but with reduced telomeres due to affected telomerase, the chromosomes may join by non-homologous end joining (NHEJ) and can lead to malignancy. This study shows that syndromes such as dyskeratosis congenita (DC), idiopathic pulmonary fibrosis (IPF), and aplastic anemia are caused by the telomere shortening. IPF syndrome is the most common manifestation of the telomere shortening. Thus this provides evidence that short telomeres are sufficient to cause common, age-related diseases. Treatment for these diseases involves organ transplantation such as liver, lung, bone marrow. Although this organ transplantation provides improved physical condition for patients, it does not address the actual cause, which is short telomeres. In recent times, telomerase activators such as TA-65 has gained commercial interest. It is also reported that sex hormones activate TERT transcription.
\nThe understanding of the role of telomere and telomerase in aging and some diseases can open new possibilities in understanding the genetic factors that play important role in the origin and augmentation of several other diseases.
\nSN is thankful to University Grants Commission, New Delhi, India. The author is thankful to Dr. Rakesh Kundu for his technical assistance and constant encouragement.
\nThe author declares no conflict of interest.
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I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. 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As a high number of molecules are available, synthesis of the most important cytokines, including tumor factor necrosis, interferons and interleukins will be presented. Here we also describe the relationships between those cytokines with some autoimmune diseases that are promoted by them.",book:{id:"6243",slug:"autoantibodies-and-cytokines",title:"Autoantibodies and Cytokines",fullTitle:"Autoantibodies and Cytokines"},signatures:"Vinicius L. Ferreira, Helena H.L. Borba, Aline de F. 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In recent years, numerous works have demonstrated that DCs and NK cells mutually influence each other with major consequences in the type and effectiveness of elicited immune responses. Among other effects, DC-NK crosstalk can result in NK cell activation and DC maturation or deletion, depending on its activation status. In this chapter and after a brief overview of DCs and NK immunobiology, we focus on the process of DC-NK crosstalk, highlighting the relevance of rationally exploring this interplay in the development of more effective cancer immunotherapies.",book:{id:"7248",slug:"dendritic-cells",title:"Dendritic Cells",fullTitle:"Dendritic Cells"},signatures:"João Calmeiro, Mylene Carrascal, Célia Gomes, Amílcar Falcão,\nMaria Teresa Cruz and Bruno Miguel Neves",authors:[{id:"114266",title:"Prof.",name:"Bruno",middleName:"Miguel",surname:"Neves",slug:"bruno-neves",fullName:"Bruno Neves"},{id:"115592",title:"Prof.",name:"Maria Teresa",middleName:null,surname:"Cruz",slug:"maria-teresa-cruz",fullName:"Maria Teresa Cruz"},{id:"233883",title:"Prof.",name:"Amílcar",middleName:null,surname:"Falcão",slug:"amilcar-falcao",fullName:"Amílcar Falcão"},{id:"243998",title:"MSc.",name:"João",middleName:null,surname:"Calmeiro",slug:"joao-calmeiro",fullName:"João Calmeiro"},{id:"244001",title:"Dr.",name:"Mylene",middleName:null,surname:"Carrascal",slug:"mylene-carrascal",fullName:"Mylene Carrascal"},{id:"244004",title:"Dr.",name:"Célia",middleName:null,surname:"Gomes",slug:"celia-gomes",fullName:"Célia Gomes"}]},{id:"62945",doi:"10.5772/intechopen.79926",title:"Dendritic Cell Subsets, Maturation and Function",slug:"dendritic-cell-subsets-maturation-and-function",totalDownloads:2288,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"Dendritic cells (DCs) are the most efficient and professional antigen-presenting cells of the immune system required for induction and dispersion of immune responses. DCs also have an important role in the induction and maintenance of tolerance. In response to infections, DCs drive the production of effector CD4+ T helper 1 (Th1) and CD8+ T cell-dominated immune responses. DCs can be designated to become tolerogenic and enhance regulatory T cells (Tregs) that regulate effector T cell responses, a process that is essential for the maintenance of immune homeostasis and control of autoimmune diseases and hypersensitivities. DCs can exist in three states: immature, semi-mature, and mature DCs. The difference between immature and mature DCs is distinctly based on variations occurring on a phenotypic level and functional level. Immature dendritic cells manifested characteristics of primitive cells, defined by expression of classical dendritic cell surface markers CD11c, CD11b and major histocompatibility complex class II (MHC-II). Phenotypic maturation is accomplished when DCs upregulate surface maturation markers such as CD80, CD83, and CD86.",book:{id:"7248",slug:"dendritic-cells",title:"Dendritic Cells",fullTitle:"Dendritic Cells"},signatures:"Ghada Mohammad Zaki Al-Ashmawy",authors:[{id:"255240",title:"Dr.",name:"Ghada",middleName:null,surname:"Al-Ashmawy",slug:"ghada-al-ashmawy",fullName:"Ghada Al-Ashmawy"}]},{id:"63198",doi:"10.5772/intechopen.79273",title:"Dendritic Cells: The Tools for Cancer Treatment",slug:"dendritic-cells-the-tools-for-cancer-treatment",totalDownloads:1196,totalCrossrefCites:2,totalDimensionsCites:7,abstract:"During cancer immune editing, the immune system shapes tumor fate in three phases through the activation of innate and adaptive immune mechanisms. After the elimination and equilibrium phase, the escape phase represents the final phase in which immunologically sculpted tumors begin to grow progressively. In this chapter, we will discuss which efforts are made to restore the balance in favor of the immune system making use of dendritic cells (DCs). The first approach is adoptive cell transfer, in which autologous DCs are generated and activated ex vivo. Secondly, we will discuss attempts in which pro-inflammatory or pro-migratory factors are delivered to attract and activate DCs in situ. Both strategies have the general goal to activate and mature DCs able to induce a robust tumor-specific T cell response. In addition, this chapter will discuss the clinical impact of DC-based therapies in cancer treatment focusing on the safety, feasibility, immunological responses, and clinical outcome.",book:{id:"7248",slug:"dendritic-cells",title:"Dendritic Cells",fullTitle:"Dendritic Cells"},signatures:"Hanne Locy, Sarah Melhaoui, Sarah K. Maenhout and Kris\nThielemans",authors:[{id:"253469",title:"Prof.",name:"Kris",middleName:null,surname:"Thielemans",slug:"kris-thielemans",fullName:"Kris Thielemans"},{id:"260847",title:"Mrs.",name:"Hanne",middleName:null,surname:"Locy",slug:"hanne-locy",fullName:"Hanne Locy"},{id:"260848",title:"MSc.",name:"Sarah",middleName:null,surname:"Melhaoui",slug:"sarah-melhaoui",fullName:"Sarah Melhaoui"},{id:"260849",title:"Dr.",name:"Sarah Karen",middleName:null,surname:"Maenhout",slug:"sarah-karen-maenhout",fullName:"Sarah Karen Maenhout"}]}],mostDownloadedChaptersLast30Days:[{id:"59914",title:"Cytokines and Interferons: Types and Functions",slug:"cytokines-and-interferons-types-and-functions",totalDownloads:5541,totalCrossrefCites:12,totalDimensionsCites:29,abstract:"This chapter aims to describe and review the main important cytokines types (notably interferons), including their biological activities, functions and structures. As a high number of molecules are available, synthesis of the most important cytokines, including tumor factor necrosis, interferons and interleukins will be presented. Here we also describe the relationships between those cytokines with some autoimmune diseases that are promoted by them.",book:{id:"6243",slug:"autoantibodies-and-cytokines",title:"Autoantibodies and Cytokines",fullTitle:"Autoantibodies and Cytokines"},signatures:"Vinicius L. Ferreira, Helena H.L. Borba, Aline de F. Bonetti, Leticia P.\nLeonart and Roberto Pontarolo",authors:null},{id:"62945",title:"Dendritic Cell Subsets, Maturation and Function",slug:"dendritic-cell-subsets-maturation-and-function",totalDownloads:2288,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"Dendritic cells (DCs) are the most efficient and professional antigen-presenting cells of the immune system required for induction and dispersion of immune responses. DCs also have an important role in the induction and maintenance of tolerance. In response to infections, DCs drive the production of effector CD4+ T helper 1 (Th1) and CD8+ T cell-dominated immune responses. DCs can be designated to become tolerogenic and enhance regulatory T cells (Tregs) that regulate effector T cell responses, a process that is essential for the maintenance of immune homeostasis and control of autoimmune diseases and hypersensitivities. DCs can exist in three states: immature, semi-mature, and mature DCs. The difference between immature and mature DCs is distinctly based on variations occurring on a phenotypic level and functional level. Immature dendritic cells manifested characteristics of primitive cells, defined by expression of classical dendritic cell surface markers CD11c, CD11b and major histocompatibility complex class II (MHC-II). Phenotypic maturation is accomplished when DCs upregulate surface maturation markers such as CD80, CD83, and CD86.",book:{id:"7248",slug:"dendritic-cells",title:"Dendritic Cells",fullTitle:"Dendritic Cells"},signatures:"Ghada Mohammad Zaki Al-Ashmawy",authors:[{id:"255240",title:"Dr.",name:"Ghada",middleName:null,surname:"Al-Ashmawy",slug:"ghada-al-ashmawy",fullName:"Ghada Al-Ashmawy"}]},{id:"64077",title:"Role of Dendritic Cells in Parasitic Infections",slug:"role-of-dendritic-cells-in-parasitic-infections",totalDownloads:1443,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Dendritic cells comprise a complex array of cell populations that play a leading role in immune defense. In an immature state, they have the capacity to sense and uptake different antigens. Upon capturing antigens, they become activated, mature, and migrate to lymph nodes where they present antigen-derived peptides to naïve T cells. Due to these excellent surveillance properties, dendritic cells play an important role against parasitic infections. Also, dendritic cells are an important source of IL-12, which is a fundamental proinflammatory cytokine in the control of intracellular parasites. The aim of this chapter is to review the most important characteristics and functions of dendritic cells and their role in the control of infection by parasites.",book:{id:"7248",slug:"dendritic-cells",title:"Dendritic Cells",fullTitle:"Dendritic Cells"},signatures:"Laila Gutiérrez-Kobeh, Jorge Rodríguez-González, Jesús Argueta-\nDonohué, Rosalino Vázquez-López and Arturo A. Wilkins-\nRodríguez",authors:[{id:"233494",title:"Dr.",name:"Laila",middleName:null,surname:"Gutiérrez-Kobeh",slug:"laila-gutierrez-kobeh",fullName:"Laila Gutiérrez-Kobeh"},{id:"239829",title:"BSc.",name:"Arturo Alfredo",middleName:null,surname:"Wilkins-Rodriguez",slug:"arturo-alfredo-wilkins-rodriguez",fullName:"Arturo Alfredo Wilkins-Rodriguez"},{id:"241093",title:"MSc.",name:"Jorge",middleName:null,surname:"Rodríguez-González",slug:"jorge-rodriguez-gonzalez",fullName:"Jorge Rodríguez-González"},{id:"241094",title:"Dr.",name:"Rosalino",middleName:null,surname:"Vázquez-López",slug:"rosalino-vazquez-lopez",fullName:"Rosalino Vázquez-López"},{id:"259995",title:"MSc.",name:"Jesús",middleName:null,surname:"Argueta-Donohué",slug:"jesus-argueta-donohue",fullName:"Jesús Argueta-Donohué"}]},{id:"60035",title:"Autoantibody-Based Diagnostic Biomarkers: Technological Approaches to Discovery and Validation",slug:"autoantibody-based-diagnostic-biomarkers-technological-approaches-to-discovery-and-validation",totalDownloads:1475,totalCrossrefCites:4,totalDimensionsCites:6,abstract:"Autoantibodies produced against self-antigens, or ‘autoantigens’, result from a loss of self-tolerance triggered by genetic and/or environmental factors which induce the immune system to attack the host’s own cells, resulting in a condition referred to as autoimmunity. In classic autoimmune diseases, it is well established that the pathology relates directly to the autoantibodies. However, it is increasingly recognised that autoantibodies are also found in many other disease areas, including cancers, cardiovascular and neurodegenerative diseases, as well infectious diseases such as malaria, albeit in such diseases it is unclear whether the autoantibodies play a direct role in the pathology or whether they are merely symptomatic of disease. Irrespective of whether they are causative or symptomatic of specific diseases though, there is increasing interest globally in exploring the clinical potential of circulating autoantibodies as diagnostic biomarkers. This chapter provides an overview of the diagnostic utility of autoantibody biomarkers in a range of disease areas and discusses their potential utility in disease staging, treatment monitoring and in prediction of immune-related adverse events. It also provides an overview of traditional and contemporary technological approaches to autoantibody biomarker discovery and validation, focusing on protein microarrays that are ideally suited to this important area of research.",book:{id:"6243",slug:"autoantibodies-and-cytokines",title:"Autoantibodies and Cytokines",fullTitle:"Autoantibodies and Cytokines"},signatures:"Farhanah Aziz, Muneera Smith and Jonathan M Blackburn",authors:null},{id:"62204",title:"Highlighting the Role of DC-NK Cell Interplay in Immunobiology and Immunotherapy",slug:"highlighting-the-role-of-dc-nk-cell-interplay-in-immunobiology-and-immunotherapy",totalDownloads:1855,totalCrossrefCites:5,totalDimensionsCites:10,abstract:"Dendritic cells (DCs) and natural killer (NK) cells are both part of the innate immune system, also playing crucial functions in the regulation of adaptive immune responses. In recent years, numerous works have demonstrated that DCs and NK cells mutually influence each other with major consequences in the type and effectiveness of elicited immune responses. Among other effects, DC-NK crosstalk can result in NK cell activation and DC maturation or deletion, depending on its activation status. 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She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}]},{type:"book",id:"7139",title:"Current Approaches in Orthodontics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7139.jpg",slug:"current-approaches-in-orthodontics",publishedDate:"April 10th 2019",editedByType:"Edited by",bookSignature:"Belma Işık Aslan and Fatma Deniz Uzuner",hash:"2c77384eeb748cf05a898d65b9dcb48a",volumeInSeries:2,fullTitle:"Current Approaches in Orthodontics",editors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. 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Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. 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