Hot tearing index (HTI) of different Al-Cu-Mn-Zr alloys with varying Ti content.
\\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:"6677",leadTitle:null,fullTitle:"Recent Advances in Neurodegeneration",title:"Recent Advances in Neurodegeneration",subtitle:null,reviewType:"peer-reviewed",abstract:"This Edited Volume Recent Advances in Neurodegeneration is a is a collection of reviewed and relevant research chapters, offering a comprehensive overview of recent developments in the field of neurodegeneration. The book comprises single chapters authored by various researchers and edited by an expert active in the neurodegeneration research area. All chapters are complete in itself but united under a common research study topic. This publication aims at providing a thorough overview of the latest research efforts by international authors on neurodegeneration, and open new possible research paths for further novel developments.",isbn:"978-1-83881-234-8",printIsbn:"978-1-83881-233-1",pdfIsbn:"978-1-83881-235-5",doi:"10.5772/intechopen.71995",price:100,priceEur:109,priceUsd:129,slug:"recent-advances-in-neurodegeneration",numberOfPages:100,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"65c05412d2a2f134e3eaa811c921273e",bookSignature:"Antonella Borreca",publishedDate:"October 9th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/6677.jpg",numberOfDownloads:4857,numberOfWosCitations:3,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:10,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:19,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 12th 2017",dateEndSecondStepPublish:"January 11th 2018",dateEndThirdStepPublish:"March 3rd 2018",dateEndFourthStepPublish:"May 22nd 2018",dateEndFifthStepPublish:"July 21st 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"192832",title:"Dr.",name:"Antonella",middleName:null,surname:"Borreca",slug:"antonella-borreca",fullName:"Antonella Borreca",profilePictureURL:"https://mts.intechopen.com/storage/users/192832/images/system/192832.jpg",biography:"Antonella Borreca is a molecular biologist specialized in the field of neuroscience. She received a master degree in Biology at University of Naples and immediately after a PhD in Neuroscience. During her PhD she specialized in Neurogenetic aiming to identify new gene or new mutation in neurodegenerative disease. Then she moved in Belgium for a post doc and she specialized in molecular neuroscience, studying molecular mechanism of Fragile X Syndrome. She then returned back to Italy where she improved her career and expertise within behavioural field. Thanks to her expertise she is able to deeply analyze different aspects of neuroscience field. She participated in different international meetings and collaborated with group in Rome but also Milan, USA, etc. Actually her research is focused on the molecular mechanism of APP expression in normal and pathological condition in AD mice model (Tg2576). In particular, she analyzed the role of RNA Binding Protein (RBPs) in the APP metabolism and their regulation in APP expression, since APP is found overexpressed in AD patient with Swedish mutation (Johnston et al., 1994) but also in sporadic cases (Vignini et al., 2014; Borreca et al., 2015).\r\nShe has also observed an unbalance of two specific RBPs in the AD mice model and synaptosomes of AD sporadic patient: hnRNP C and FMRP (Borreca et al., 2015). She focused the research on the role of the protein synthesis machinery in the Alzheimer disease. In particular she analyzed the protein synthesis in the early phase of the pathology and distribution of APP mRNA on polysome fractionation as well as the role of some protein synthesis molecule in the Alzheimer pathology (Borreca et al., 2017 in preparation).",institutionString:"National Research Council",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"National Research Council",institutionURL:null,country:{name:"Italy"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1056",title:"Neurology",slug:"neurology"}],chapters:[{id:"68996",title:"Introductory Chapter: A Common Feature of Neurodegenerative Disorders",doi:"10.5772/intechopen.84132",slug:"introductory-chapter-a-common-feature-of-neurodegenerative-disorders",totalDownloads:708,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Antonella Borreca",downloadPdfUrl:"/chapter/pdf-download/68996",previewPdfUrl:"/chapter/pdf-preview/68996",authors:[{id:"192832",title:"Dr.",name:"Antonella",surname:"Borreca",slug:"antonella-borreca",fullName:"Antonella Borreca"}],corrections:null},{id:"63664",title:"Neuroprotective Strategies of Blood-Brain Barrier Penetrant “Forskolin” (AC/cAMP/PKA/CREB Activator) to Ameliorate Mitochondrial Dysfunctioning in Neurotoxic Experimental Model of Autism",doi:"10.5772/intechopen.80046",slug:"neuroprotective-strategies-of-blood-brain-barrier-penetrant-forskolin-ac-camp-pk-sub-a-sub-creb-acti",totalDownloads:882,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"New developments in the study of brain are among the most exciting frontiers of contemporary neuroscientific research for the clinical practitioner. Increasing knowledge of neurocomplications and of their discrete localization in the various regions of brain permits new modes of pharmacological management of some major neurological disorders like autism. The research work reported in this scheme is undertaken with an objective to explore the potential molecular targets (AC/cAMP/PKA/CREB) for the development of newer therapeutics strategies (forskolin) for the management of neurological disorders and associated symptoms. Studies aimed at addressing these questions have fallen into two main categories: in-vivo behavioral paradigms and in-vitro differentiation biochemical, morphological and histopathological analysis. Therefore, first time, we aim to gather the propensity of mitochondrial cofactors, neuropathological mechanisms and various diagnostic methods to explore the clinical therapeutic strategies to ameliorate the neurodevelopmental disorder autism.",signatures:"Sidharth Mehan, Himanshi Khera and Ramit Sharma",downloadPdfUrl:"/chapter/pdf-download/63664",previewPdfUrl:"/chapter/pdf-preview/63664",authors:[{id:"244651",title:"Dr.",name:"Sidharth",surname:"Mehan",slug:"sidharth-mehan",fullName:"Sidharth Mehan"},{id:"246866",title:"Dr.",name:"Jeremiah",surname:"Ogbadu",slug:"jeremiah-ogbadu",fullName:"Jeremiah Ogbadu"},{id:"246867",title:"Dr.",name:"Mamtaj",surname:"Alam",slug:"mamtaj-alam",fullName:"Mamtaj Alam"},{id:"246868",title:"Dr.",name:"Rishabh",surname:"Jhanji",slug:"rishabh-jhanji",fullName:"Rishabh Jhanji"},{id:"246869",title:"Dr.",name:"Devesh",surname:"Agarwal",slug:"devesh-agarwal",fullName:"Devesh Agarwal"},{id:"246870",title:"Dr.",name:"Shakshi",surname:"Sharma",slug:"shakshi-sharma",fullName:"Shakshi Sharma"},{id:"246871",title:"Dr.",name:"Aakriti",surname:"Garg",slug:"aakriti-garg",fullName:"Aakriti Garg"},{id:"246872",title:"Dr.",name:"Tarun",surname:"Kapoor",slug:"tarun-kapoor",fullName:"Tarun Kapoor"},{id:"246873",title:"Prof.",name:"Ramit",surname:"Sharma",slug:"ramit-sharma",fullName:"Ramit Sharma"},{id:"246874",title:"Dr.",name:"Raju",surname:"Paudel",slug:"raju-paudel",fullName:"Raju Paudel"},{id:"246875",title:"Dr.",name:"Urvashi",surname:"Langeh",slug:"urvashi-langeh",fullName:"Urvashi Langeh"},{id:"246877",title:"Dr.",name:"Pallavi",surname:"Duggal",slug:"pallavi-duggal",fullName:"Pallavi Duggal"},{id:"246878",title:"Dr.",name:"Kajal",surname:"Rajdev",slug:"kajal-rajdev",fullName:"Kajal Rajdev"},{id:"247050",title:"Dr.",name:"Khadga",surname:"Raj",slug:"khadga-raj",fullName:"Khadga Raj"},{id:"264529",title:"Ms.",name:"Shivani",surname:"Verma",slug:"shivani-verma",fullName:"Shivani Verma"},{id:"264530",title:"Ms.",name:"Himanshi",surname:"Khera",slug:"himanshi-khera",fullName:"Himanshi Khera"}],corrections:null},{id:"62980",title:"From Neuronal Differentiation of iPSCs to 3D Neural Organoids: Modeling of Neurodegenerative Diseases",doi:"10.5772/intechopen.80055",slug:"from-neuronal-differentiation-of-ipscs-to-3d-neural-organoids-modeling-of-neurodegenerative-diseases",totalDownloads:1121,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"In the last decade, the finding that somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) leads to a great improvement of research involving the use of differentiated stem cells as model of diseases. In the field of neurodegeneration, iPSC technology allowed to culture in vitro all the types of patient-specific neurons, not only helping the discovery of diseases’ etiopathology but also testing new drugs with a personalized medicine approach. Moreover, iPSCs can be combined with the 3D bioprinting technology, allowing physiological cell-to-cell interactions, given by a combination of several biomaterials, scaffolds, and cells. This technology combines bioplotter and biomaterials which can encapsulate several types of cells, e.g., iPSCs or differentiated neurons, to develop an innovative cellular model. iPSCs and 3D cell cultures’ technologies represent the first step to obtain a more reliable model, like an organoid to facilitate neurodegenerative diseases’ investigation.",signatures:"Matteo Bordoni, Valentina Fantini, Orietta Pansarasa and Cristina Cereda",downloadPdfUrl:"/chapter/pdf-download/62980",previewPdfUrl:"/chapter/pdf-preview/62980",authors:[{id:"86115",title:"Dr.",name:"Cristina",surname:"Cereda",slug:"cristina-cereda",fullName:"Cristina Cereda"},{id:"186226",title:"Dr.",name:"Orietta",surname:"Pansarasa",slug:"orietta-pansarasa",fullName:"Orietta Pansarasa"},{id:"243760",title:"Dr.",name:"Matteo",surname:"Bordoni",slug:"matteo-bordoni",fullName:"Matteo Bordoni"},{id:"243761",title:"MSc.",name:"Valentina",surname:"Fantini",slug:"valentina-fantini",fullName:"Valentina Fantini"}],corrections:null},{id:"63720",title:"Molecular Basis of Neurodegeneration: Lessons from Alzheimer’s and Parkinson’s Diseases",doi:"10.5772/intechopen.81270",slug:"molecular-basis-of-neurodegeneration-lessons-from-alzheimer-s-and-parkinson-s-diseases",totalDownloads:1251,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Alzheimer’s disease (AD) and Parkinson’s disease (PD) constitute the main causes of dementia worldwide and the major health threats to elderly people. Moreover, with the ageing of the global population, neurodegenerative disorders, such as AD and PD, constitute a major public health issue. Regrettably, significant advances regarding the molecular aspects of these diseases have not yet been translated into real improvements in AD/PD therapeutics. In this regard, both AD and PD are highly complex and involve critical molecular events governing the establishment and progression of each disease. Moreover, molecular alterations trigger pathophysiological cascades involving the immune/inflammatory response, oxidative stress, and mitochondrial dysfunction, among others, ultimately leading to neuronal death. Similarly, these alterations also affect glial cells and brain vasculature, which contribute directly to the progression of these disorders. Accordingly, the present paper aims to summarise the main molecular elements related to AD and PD as well as the pathophysiological implications of such alterations to improve our understanding of the cellular and molecular responses observed during neurodegeneration. We believe that providing a more comprehensive view of the pathophysiological cascade, including neurons and glial cells, might prompt researchers to widen neurodegenerative disorder research and therapeutic approaches.",signatures:"Juan M. Zolezzi, Sussy Bastías-Candia and Nibaldo C. Inestrosa",downloadPdfUrl:"/chapter/pdf-download/63720",previewPdfUrl:"/chapter/pdf-preview/63720",authors:[{id:"157413",title:"Dr.",name:"Nibaldo C.",surname:"Inestrosa",slug:"nibaldo-c.-inestrosa",fullName:"Nibaldo C. Inestrosa"},{id:"203006",title:"Dr.",name:"Juan M.",surname:"Zolezzi",slug:"juan-m.-zolezzi",fullName:"Juan M. Zolezzi"},{id:"235175",title:"Dr.",name:"Sussy",surname:"Bastías-Candia",slug:"sussy-bastias-candia",fullName:"Sussy Bastías-Candia"}],corrections:null},{id:"63612",title:"Neurodegenerative Diseases Associated with Mutations in SLC25A46",doi:"10.5772/intechopen.79992",slug:"neurodegenerative-diseases-associated-with-mutations-in-em-slc25a46-em-",totalDownloads:896,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Neurodegenerative diseases present substantial clinical challenges. Their processes have been linked with various genetic causes, including mutations of genes encoding proteins associated with mitochondrial dynamics. Biallelic mutations in SLC25A46 have been identified as novel causes of a wide spectrum of neurological diseases with recessive inheritance, including optic atrophy, Charcot-Marie-Tooth neuropathy (CMT) type 2A neuropathy, Leigh syndrome, progressive myoclonic ataxia, and lethal congenital pontocerebellar hypoplasia. SLC25A46 (solute carrier family 25 member 46) is a membrane transit protein that is expressed in the mitochondrial outer membrane where it plays a major role in mitochondrial dynamics and cristae maintenance. This chapter presents recent findings on: (1) the clinical heterogeneity of SLC25A46-related neuropathies; (2) the SLC25A46 mutation spectrum and associated genotype-phenotype correlation; and (3) pathophysiological functions of SLC25A46 as characterized in cells and mouse models. A better understanding of the etiology of SLC25146-linked diseases will elucidate therapeutic perspectives.",signatures:"Zhuo Li, Jesse Slone, Lingqian Wu and Taosheng Huang",downloadPdfUrl:"/chapter/pdf-download/63612",previewPdfUrl:"/chapter/pdf-preview/63612",authors:[{id:"232494",title:"Prof.",name:"Taosheng",surname:"Huang",slug:"taosheng-huang",fullName:"Taosheng Huang"},{id:"249418",title:"Dr.",name:"Zhuo",surname:"Li",slug:"zhuo-li",fullName:"Zhuo Li"},{id:"249420",title:"Dr.",name:"Jesse",surname:"Slone",slug:"jesse-slone",fullName:"Jesse Slone"},{id:"249422",title:"Prof.",name:"Lingqian",surname:"Wu",slug:"lingqian-wu",fullName:"Lingqian Wu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"745",title:"Neurodegenerative Diseases",subtitle:"Processes, Prevention, Protection and 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\r\n\tThoughts, emotions, behaviors, and body sensations are interrelated, and a change in one of these structures can affect the others. Today, cognitive-behavioral therapy (CBT) is in the position of a psychotherapy school with a wide application area, which includes a group psychotherapy approach based on this view. CBT is an effective treatment approach for many mental disorders/problems such as depression, anxiety disorders, alcohol-substance use disorders, marital problems, eating disorders, and severe mental disorders. Numerous studies have demonstrated the positive effect of CBT on functionality and quality of life. Since its emergence, CBT has made significant advances in clinical practice and research. This book will cover the historical development, basic principles, and application areas of CBT. It is aimed that the book chapters are prepared in the light of current literature findings will be an essential reference source for the readers.
",isbn:"978-1-83969-897-2",printIsbn:"978-1-83969-896-5",pdfIsbn:"978-1-83969-898-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"849acf69df0db62876816078930b4481",bookSignature:"Prof. Cicek Hocaoglu",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11890.jpg",keywords:"Exposure, Homework Assignments, Formulation, Treatment Rationale, Depression, Anxiety Disorders, Eating Disorders, Personality Disorders, Obsessive Compulsive Disorder, Cognitive Behavioral Therapy, Psychotherapy, Dysthymia",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 3rd 2022",dateEndSecondStepPublish:"July 6th 2022",dateEndThirdStepPublish:"September 4th 2022",dateEndFourthStepPublish:"November 23rd 2022",dateEndFifthStepPublish:"January 22nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Cicek Hocaoglu received postgraduate training in psychiatry at the Medical School of Karadeniz Technical University. She is currently a Professor and Head of the Department of Psychiatry at the Recep Tayyip Erdogan University Medical School. She has published over 100 national/international scientific articles, book chapters, and papers presented. Her interests include consultation-liaison psychiatry, suicide, schizophrenia, anxiety disorders, bipolar disorder, and psychopharmacology.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"28322",title:"Prof.",name:"Cicek",middleName:null,surname:"Hocaoglu",slug:"cicek-hocaoglu",fullName:"Cicek Hocaoglu",profilePictureURL:"https://mts.intechopen.com/storage/users/28322/images/system/28322.jpg",biography:"Cicek Hocaoglu obtained her medical degree from Uludag University Faculty of Medicine, Bursa, Turkey. She received postgraduate training in psychiatry at the Medical School of Karadeniz Technical University, Trabzon, Turkey. She is currently Professor and Head of the Department of Psychiatry at the Recep Tayyip Erdogan University Medical School, Rize, Turkey. She has many published national/international scientific articles, book chapters, and papers presented in congresses. Her interests include consultation-liaison psychiatry, suicide, schizophrenia, anxiety disorders, bipolar disorder, and psychopharmacology.",institutionString:"Recep Tayyip Erdoğan University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Recep Tayyip Erdoğan University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"466997",firstName:"Patricia",lastName:"Kerep",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/466997/images/21565_n.jpg",email:"patricia@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully"}},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9500",title:"Recent Advances in Bone Tumours and Osteoarthritis",subtitle:null,isOpenForSubmission:!1,hash:"ea4ec0d6ee01b88e264178886e3210ed",slug:"recent-advances-in-bone-tumours-and-osteoarthritis",bookSignature:"Hiran Amarasekera",coverURL:"https://cdn.intechopen.com/books/images_new/9500.jpg",editedByType:"Edited by",editors:[{id:"67634",title:"Dr.",name:"Hiran",surname:"Amarasekera",slug:"hiran-amarasekera",fullName:"Hiran Amarasekera"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3828",title:"Application of Nanotechnology in Drug Delivery",subtitle:null,isOpenForSubmission:!1,hash:"51a27e7adbfafcfedb6e9683f209cba4",slug:"application-of-nanotechnology-in-drug-delivery",bookSignature:"Ali Demir Sezer",coverURL:"https://cdn.intechopen.com/books/images_new/3828.jpg",editedByType:"Edited by",editors:[{id:"62389",title:"PhD.",name:"Ali Demir",surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"31723",title:"Gender-Specific Aspects in the Clinical Presentation of Cardiovascular Disease",doi:"10.5772/32282",slug:"gender-specific-aspects-in-the-clinical-presentation-of-cardiovascular-disease",body:'\n\t\tIn the industrialized countries, the cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women after of 50 years. Genetic, hormonal and metabolic influences are involved in gender differences, including the epidemiology, symptoms, diagnosis, progression, prognosis and management of these pathologies.
\n\t\t\tRecent advances in the field of cardiovascular medicine have not led to significant drops in case fatality rates for women, compared to the dramatic reductions achieved for men. Such gender-specific difference in cardiovascular disease mortality are probably related to a knowledge gap about CVD in women. Thus, much of the evidence supporting contemporary recommendations for testing, prevention, and treatment of CVD in women is extrapolated from studies conducted predominantly on middle-aged men. For example pharmacological therapy is hampered by defective evidence.
\n\t\t\tOnly recently, significant sex-related differences in prevalence, presentation, management and outcomes of CVD, have been evaluated and discovered.
\n\t\t\tThe ability of knowing and recognizing gender differences in CVD may facilitate a rapid identification of cardiac signs and symptoms of warning and may avoid significant delays in diagnosis and treatment in women. This compendium will briefly summarize gender-related differences in several manifestations of CVD, with a special focus also on arrhythmias and heart failure.
\n\t\tTraditionally, guidelines classify women as being at high, intermediate or low risk on risk profile, based on Framingham risk scores. Despite major traditional risk factors are the same in both sexes, gender-specific differences are noted, and these differences are related to different outcome. For this reason, a new approach in evaluation of cardiovascular risk in women considers a multifactorial model that includes a complex interaction between sex hormones and traditional risk factors.
\n\t\t\tThere is also substantial gender-related differences in the prevalence and outcome in traditional risk factors. For example, overall rates of hypertension and smoking are higher in men, but their presence is associated with a worse outcome in women. The prevalence of hypertension is lower in pre-menopausal women than men, whereas in post-menopausal women it is higher than in men. In fact about 50% of post-menopausal women experience of moderate to severe hypertension or take antihypertensive therapy.
\n\t\t\t\tSeveral studies have clearly demonstrated a strong relationship between level of blood pressure and risk for cardiovascular events. In this setting, hypertension is one of the most risk factors for stroke, myocardial infarction, heart failure, aortic disease and chronic renal failure. Mechanisms responsible for the increase in blood pressure in post-menopausal women are complex and multifactorial, including loss of estrogen, oxidative stress, endothelial dysfunction, modification in renin-angiotensin system and sympathetic activation.
\n\t\t\t\tHypertension may appears as an isolated disease, more typical of elderly women, or as part of the metabolic syndromes (MS), more frequently in early postmenopausal women. MS is a constellation of interrelated risk factors that promote the development of CVD. The presence of MS worsens the severity of hypertension and reduces the response to treatment. Than, MS is considered a unfavourable prognostic factor in hypertension post-menopausal women. On the other hand hypertension tends to associate with other metabolic risk factors and about one-half patients with essential hypertension are insulin resistant. In addition women with MS have chronic subclinical inflammation and systemic endothelial dysfunction. Endothelial dysfunction is common after the menopause and its detection may precede overt disease such as hypertension and diabetes.
\n\t\t\t\tData derived from population studies demonstrate that total cholesterol measurements are higher in men until the fifth decade of life but, beyond this age, women have greater values. Examining the lipoprotein subclassis, women have less LDL particles than men and have about two-fold higher concentration of HDL particles then men. Particularly, HDL cholesterol inversely correlates with coronary artery disease (CAD) in young men and in women of all ages. Women typically experience a relatively mild decline in HDL cholesterol at the time of menopause.
\n\t\t\t\tHypertriglyceridemia is also a more potent independent risk factor for CAD in women as compared with men. In fact, in presence of hypertriglyceridemia, the risk of CVD is twice in women.
\n\t\t\t\tAnother strong risk factors in women is diabetes. Diabetic women have significantly higher cardiovascular mortality when compared with diabetic men, because diabetes eliminates the ‘female advantage’ of a lower CAD prevalence and outcome risk that exists for the female in general population. Furthermore diabetes is an independent predictor of ‘atypical’ presentation of acute myocardial infarction in women.
\n\t\t\t\tAt the onset of diabetes-related cardiovascular complications, women have higher out-of-hospital mortality than men, and those who reach hospital are more likely to die from an initial cardiac event and are also at high risk of post-event complications.
\n\t\t\tOther factors are unique to the female: menopause, which affects especially if early and hypothalamic-hypoestrogenism occurring in fertile women.
\n\t\t\t\tMenopause is a physiological condition associated with endothelial dysfunction, due to lack of estrogens. Than, the deficiency of female gonadal hormones may represent a major risk factor for menopausal hypertension, due to related modifications of blood vessel structure and the elicit response to a vasoactive substances.
\n\t\t\t\tFurthermore, dysfunction of the endotelium causes reduction or abolition of vasoprotective factors, inducing a proinflammatory, proliferative and procoagulatory milieu. These changes favour the development of cardiovascular risk factors, as hypertension.
\n\t\t\t\tGender-specific opportunities for identifying women’s risk (e.g., prior preeclampsia) also deserve further exploration.
\n\t\t\t\tPreeclampsia is a disorder of pregnancy diagnosed by gestational hypertension and proteinuria. Abnormal placentation resulting in preeclampsia and intrauterine growth restriction is a major cause of both maternal and perinatal morbidity and mortality.
\n\t\t\t\tPrior preeclampsia is associated with increased risk of CVD, including myocardial infarction, ischemic heart disease, stroke and endstage renal disease. Particularly, the increased risk for future vascular disease is more pronounced in women with early-onset preclampsia. Although the symptoms of preeclampsia resolve over a number of weeks after delivery, maternal vascular dysfunction may persist for years.
\n\t\t\t\tEndothelial dysfunction, however, is considered a central component of the pathophysiology of preeclampsia and known to contribute to the pathogenesis of hypertension and cardiovascular sequelae. Several factors contribute to the endothelial dysfunction in the post-partum state. Abnormal placenta, for example, release antiangiogenic factors, harmful to the vascular endothelium. Often, women with a history of peeclampsia or intrauterine growth restriction have high cholesterol levels, high blood pressure and insulin resistance.
\n\t\t\t\tFrequently, preeclamptic women are obese, and obesity associated with insulin resistance, may reduce endothelial dependent blood flow response.
\n\t\t\t\tBehavioral factors also, such as chronic stress, lack of social support, and family demands, as well as biological processes, including genetics, may contribute to the development of CVD in this setting.
\n\t\t\t\tSimilarly, women with a history of polycystic ovary syndrome have a increased risk of CVD and have a greater frequency of multiple risk factors including central obesity, insulin resistance, and a greater prevalence of the metabolic syndrome and diabetes.
\n\t\t\tBeside the traditional and female specific risk factors, novel risk markers such as inflammatory markers are being studied.
\n\t\t\t\tWomen are at increased risk of inflammatory and autoimmune disease. The risk of mortality and morbidity from CVD is very high in autoimmune diseases, as systemic lupus erythematosus or rheumatoid arthritis. Various possible mechanisms have been proposed to explain the excess rate of cardiovascular mortality in patients with autoimmune disease.
\n\t\t\t\tA combination of traditional (dyslipidemia, hypertension, diabetes, and smoking) and nontraditional risk factors, including high inflammation, antiphospholipid antibodies and lipid oxidation, contribute to CVD in autoimmune diseases. Inflammation is a key component in the development of atherosclerosis in this setting. In fact, inflammation leads to the activation of endothelial cells, which, through an increase in the expression of leukocyte adhesion molecules, promotes a pro-atherosclerotic environment. Expression of proinflammatory cytokines and inflammatory mediators influences all stages of atherosclerosis development, from early atheroma formation to thrombus development responsible for events such as myocardial infarction. Proinflammatory cytokines may promote both traditional (e.g., dyslipidemia, insulin resistance) and nontraditional (e.g., oxidative stress) systemic cardiovascular risk factors.
\n\t\t\t\tThan in these patients, is commonly found a presence of endothelial dysfunction, a loss of arterial compliance and dysfunction in the microvascolature, resulting in myocardial flow heterogeneity.
\n\t\t\t\tOthers factors contribute to poor prognosis: undertreatment of cardiovascular comorbidity may contribute to increased cardiovascular mortality in these patients. However, some drugs, largely used in this setting, may worsen cardiovascular profile: e.g. corticosteroids promote hypertension, dyslipidemia, and diabetes.
\n\t\t\t\tThen, novel risk stratification, including inflammatory markers and reproductive hormones, is developing to assess global cardiovascular risk in women.
\n\t\t\tCoronary heart disease (CHD) is the most common cause of death amongst women, who experience more complications after acute myocardial infarction (AMI) than men.
\n\t\t\tIt has been demonstrated that the epidemiology, the clinical manifestation and the progression of CHD are different in both sexes. The women developed CHD about 10-20 years later than men, in part by the influence of hormones and in part by the genetic sex.
\n\t\t\tParticularly, at the time of first experience of AMI, women are more likely to have diabetes mellitus or heart failure (HF) than men.
\n\t\t\tIn addition, the prevalence of obstructive coronary disease is particularly low in premenopausal women, whilst increases dramatically for a woman after age 50.
\n\t\t\tThe most common initial presentation of CHD is a AMI or sudden cardiac death and up to half of all women presenting with an acute myocardial infarction report no prior chest pain symptoms. There would appear to be an interaction effect of symptom presentation with age, in that older women often present in a similar way to men.
\n\t\t\tSeveral studies have indicated that women have “atypical” symptoms such as back pain, dyspnea, indigestion, nausea/vomiting and weakness. Frequently women reported pain in the jaw and neck and describe their symptoms as more anguished and frightening (emotional component) compared with men. Furthermore, prodromal symptoms are described up to 1 month before the onset of AMI such unusual fatigue (70.7%), sleep disturbance (47.8%) and shortness of breath (42.1%). The atypical presentation may explain the rate of under-diagnosed AMI, the under treatment of acute coronary syndromes and the worse outcomes characterized by increased hospital morbidity, higher mortality and fewer evidence-based therapies in women.
\n\t\t\tIn the postmenopausal women, the plaque rupture is the main mechanism of acute coronary syndromes like as in the men. The higher mortality noted for younger women when compared with age-matched men is due the higher frequency of plaque erosion (Fig. 1). In an autopsy series, women also had a greater frequency of distal microvascular embolization in the setting of a fatal epicardial thrombosis when compared to men, independently of the type of thrombus or presence of necrosis. AMI and sudden death in women can occur also in spontaneous coronary artery dissection. This event is more frequent in the peri-partum period and can involve all coronary tree, but more frequently affects the left anterior descending artery. The dissection can involve every coronary, but in women frequently involves the left anterior descending coronary artery, whereas in man the right coronary artery is more frequently involved.
\n\t\t\tMany as 50% of patients undergoing coronary angiography for typical or atypical chest pain do not have obstructive CAD. An alternative mechanism of pain in women may be a coronary microvascular dysfunction, known as syndrome X. Most of these patients have an ‘abnormal’ exercise stress test, myocardial perfusion defects on gated Single-photon emission computed tomography or stress-induced wall motion abnormalities on echocardiography, but normal coronary angiography.
\n\t\t\tHowever, differentiation between these mechanisms of chest pain is important, because ‘noncardiac’ chest pain is not associated with cardiovascular sequelae and may require further medical evaluation and treatment. By contrast, syndrome X, which is thought to be caused by microvascular dysfunction, is associated with inducible metabolic ischaemia and can be treated by improving microvascular vasomotor tone with oral L-arginine, a precursor to vascular nitric oxide, and oestrogen.
\n\t\t\tDespite the absence of CAD and low risk for adverse cardiac events, a majority of those patients continue to have symptoms that contribute to a poor quality of life and consumption of large amounts of health care resources because of repeated evaluations and hospitalizations. Recently, Han et al. studied patients with obstructive CAD who underwent simultaneous intravascular ultrasound and coronary reactivity assessment and demonstrated that men have a greater atheroma burden and more diffuse epicardial endothelial dysfunction while women have more disease of the microcirculation. The coronary micro-vascular dysfunction, the smaller coronary artery lumens, the less collateral circulation than men and more prominent positive remodeling support the higher rate of angina, and acute coronary syndromes in the absence of obstructive CAD particularly during exertion or stress.
\n\t\t\tGender differences in plaque morphologic features in an autoptic series of patients who died for sudden cardiac death, modified from reference 13. SCD, sudden cardiac death; Th, thrombus.
The lifetime risk of developing HF is about 20% for both men and women. There are differences between men and women in clinical presentation, aetiology, treatment and outcome in HF, and these differences lead to different outcome.
\n\t\t\tThe women are older than men and present more frequent hypertension and diabetes.
\n\t\t\tDiabetes mellitus is one of the strongest additional risk factors for the development of HF in women with CAD.
\n\t\t\tThe systolic function is usually better preserved and the prevalence of ischemic etiology is lower respect to hypertension and valvular diseases. Another cause of HF includes cardiac toxicity from chemotherapeutic agents used to treat breast malignancy.
\n\t\t\tMullens et al. show that the survival rate in women with non-ischemic cardiomyopathy was better than men, irrespective of baseline characteristics, while there was no advantage in presence of ischemic cause. The reason of different outcome remains unclear but might in part be related to sex differences in etiology.
\n\t\t\tThe diagnosis of HF is a clinical diagnosis based on a constellation of symptoms and signs. Women with impaired systolic left ventricular function are more likely than men to have dependent edema, jugular venous distension, and an S3 gallop.
\n\t\t\tFurthermore, normal brain natriuretic peptide value, a biomarker used to identify patients with symptoms of HF, are higher in women versus men.
\n\t\t\tCurrent guidelines for HF therapy also are not sex specific due to under-representation of women and lack of sex-specific, prospective, randomized clinical trials. Indeed, women receive less life-prolonging treatment (ACE-I, beta-blockers and spironolactone) than men, in the presence of normal left ventricular function, while there no difference if etiology of HF is CAD.
\n\t\t\tCardiac resynchronization therapy, an important therapy for HF, is beneficial for both women and men. Data suggest CRT is preferable to medical therapy alone in women for the combined end point of total mortality and hospital stay for major cardiovascular events.
\n\t\t\tA peculiar type of left ventricular dysfunction and HF typical in women is Takotsubo cardiomyopathy. This disease is typically observed in post-menopausal women and the highest frequency of occurrence is between the seventh and eighth decade of life.
\n\t\t\tThe reason for the much more common occurrence in postmenopausal women is unclear.
\n\t\t\tIt is characterized by a left ventricular dysfunction, electrocardiographic changes like an acute myocardial infarction and release of cardiac biomarkers, in the absence of obstructive coronary disease. The emotionally or physical stress are usually the triggers. The catecholamine-mediated cardio-toxicity, multi-vessels coronary vasospasm and abnormalities in coronary micro-vascular function have been postulated as pathophysiologic mechanisms.
\n\t\t\tThe left ventricular dysfunction is reversible within weeks, despite a dramatic clinical presentation (similar to acute myocardial infarction but in the absence of obstructive coronary disease) and substantial risk of complications in the acute setting.
\n\t\t\tAnother cause of left ventricular dysfunction and HF typical in women is peripartum cardiomyopathy (PPCM). This disease develops in the last month of pregnancy or within 5 months post-partum with no pre-existing cardiac disease or identifiable cause. The incidence is very low (<1%) and varies on the basis of the population studied. Risk factors include advanced maternal age, African descent, twin pregnancy, usage of tocolytics, and poverty.
\n\t\t\tThe etiology remains unknown, but potential causes include abnormal immune response to pregnancy, increased myocyte apoptosis, genetic predisposition. Only 20% may worsen up to the death or transplantation, while one-half of PPCM patients recover normal systolic function within 6 months.
\n\t\tIt is been demonstrated that women had a higher resting heart rate than did men (3 to 5 beats faster for minute). These finding may be explained by differences in exercise tolerance, autonomic modulation and intrinsic properties of the sinus node, influencing in part by hormonal influences. Burke et al. reported an higher average heart rate during the follicular or luteal phases of the menstrual cycle, although the response to double autonomic blockade was identical regardless of phase.
\n\t\t\tSeveral authors demonstrated differences in QT interval between men and women. Women have a longer corrected QT interval and the difference becomes more pronounced at lower heart rates. Rautaharju et al. reported that this difference was due to a drop in the corrected QT that occurred in males after puberty (when androgen levels are highest). Then, the interval in men gradually increased with age until 50 years, at which point it paralleled that of women. The actions of hormonal influences in QT differences was confirmed in families with genotipically characterized long QT syndrome. In addition, the torsades de pointes correlated to both congenital and acquired long QT Syndrome was more frequent in women.
\n\t\t\tThere are many differences in incidence, prevalence, presentation and clinical course of many arrhythmias. Inappropriate sinus tachycardia is more common in women. Rodigruez et al. reported in patients undergoing invasive electrophysiologic testing for various tachycardias that the atrio-ventricular node reentrant tachycardia (AVNRT) was twice times more common in women, whereas atrial tachycardia affected both sexes equally. In addition, the atrio-ventricular reentrant (circus-movement) tachycardia (AVRT), atrial fibrillation (AF), and ventricular fibrillation (VF) occurred more often in men. These trends for supra-ventricular tachycardias (SVTs), AF, VF, were confirmed in the Framingham cohort. Myerburg and associates found that the inducing SVT during electrophysiologic testing was greatest at the onset of menses or during the premenstrual phase. Rossano et al. confirmed that the SVT prone state is hindered by estrogen and facilitated by progesterone.
\n\t\t\tThe SVTs new- onset or exacerbation are most common arrhythmia during pregnancy and the postpartum period in absence o f structural heart disease. The mechanisms for increase in this situation may be related to progesteronerich gravid state, increased intravascular volume and autonomic tone.
\n\t\t\tThe Atrial Fibrillation (AF) is the most prevalent in men, although its incidence increases with age both in men and women. Women with AF are more symptomatic, older and have lower quality of life and more co-morbidities than men. Also they present more likely a higher heart rate, longer episodes and increase incidence of embolic strokes compared to men. Data from the Euro Heart Survey on Atrial Fibrillation demonstrated that women are usually treated less aggressively, with fewer cardioversions and catheter ablations. In this study, albeit both genders received anticoagulation therapy, women experienced a significantly higher rate of stroke and major bleeding events.
\n\t\tAluminum alloys have been one of the most prominent structural material system for many years now; this is also reflected in their global usage, they come only next to steel [1, 2]. Owing to their high specific strength, resistance to stress corrosion cracking, excellent fatigue resistance, workability and cost effectiveness [3], Aluminum alloys are one of the primary material choice for aerospace and automotive industries [2, 4]. In addition, Aluminum based composites were developed over the years to mitigate some of the limitations of Aluminum alloys and further facilitates their use for various engineering applications [5]. Apart from structural applications, Aluminum and its alloys are also employed for the electronics and electrical industries in abundance for their suitable combination of functional properties [6].
Pure Aluminum is characterized by low yield strength which is improved by many folds from different strengthening strategies e.g. by adding different alloying elements, thereby making the alloys suitable for structural applications. Depending upon the major alloying element/s, Aluminum alloys are classified in two important categories; some of the alloys can be strengthened by heat treatment (age hardening) while others by mechanical deformation (non-age hardenable) [7, 8]. Al-Cu alloys fall in the first category; they are strengthened by in situ precipitates introduced through appropriate thermal treatment (aging). In age hardening, these precipitates hinder the dislocation motion and increase the hardness or strength of the alloy [9].
Despite the beneficial attributes, age-hardening Aluminum alloys, especially Al-Cu alloys suffer from limited high temperature capability. At temperature above 200°C, the metastable strengthening precipitates (e.g. θ
In recent times, a new class of Al-Cu alloys is developed by suitable micro-alloying with Mn and Zr which possesses excellent stability for strengthening θ′ precipitates at and above 300°C. The Al-Cu-Mn-Zr, termed as ACMZ alloys, provide significant improvement in most of the elevated temperature mechanical properties including hardness, tensile strength, creep and fatigue resistance etc. The present chapter provides a detailed account of the development of Al-Cu-Mn-Zr alloys while highlighting the limitations of existing Al-Cu alloys in the first place. It alongside discusses about the underlying mechanisms responsible for their excellent high temperature stability and subsequently on various properties. The chapter finally access the possibility of industrial adaptation of this newly developed alloy system and expected industrial impacts in long run.
During age hardening of Al-Cu alloys, it is first heat-treated at temperatures where single-phase α-Al solid solution is formed; this process is known as solution treatment [7]. Afterwards, the alloy is rapidly quenched to room temperature which causes freezing of solute Cu atoms within the α-Al matrix, thus forming a super saturated solid solution (SSSS). The solute atoms afterwards can diffuse even at room temperature through this super-saturated α-Al matrix and form various Al-Cu precipitates; this process is known as natural aging. In this regard, Figure 1a represents the binary Al-Cu phase diagram along with the solvus lines for various metastable precipitate phases. However, in common engineering practice, the solutionized alloy is heat treated at certain elevated temperature, usually within the two-phase region to produce various metastable precipitates depending on the heat treatment time and temperature (artificial aging). At sufficiently low aging temperature or during natural aging, Cu solute cluster first form from the quenched-in vacancies within the supersaturated α-Al matrix. These solute clusters then arrange in a single layer of Cu atoms known as
Schematics showing (a) section of Al-Cu binary phase diagram, (b) crystal structure of parent α-Al matrix and various metastable (
When the aging process continues above the GP zone solvus line (Figure 1a),
In the
The equilibrium precipitate in the Al-Cu system is tetragonal
The entire precipitation process during aging of Al-Cu alloy therefore can be summed up as:
The operating strengthening mechanism/s in Al-Cu alloy system differs as a function of precipitate type, mainly with their size and coherency with α-Al matrix. When the precipitates are small and coherent with α-Al matrix (e.g.
When the precipitates (usually
Schematic showing (a) the mechanism of Orowan looping, (b) CRSS increment as a function of precipitate radius for particle shearing and Orowan looping mechanisms, and (c) isothermal aging curves (hardness vs. aging time) for various commercial Al alloys e.g. Al-Cu (206), Al-Si-Cu (319) and Al-Si (356, A356, A356 + 0.5Cu) [
where,
where,
The CRSS increment with respect to the precipitate radius due to either particle shearing or Orowan looping is schematically represented in Figure 2b [12]. It seems that a critical radius exists for the strengthening precipitate below which particle shearing is preferred. When the precipitate grows beyond this critical radius, the dislocations prefer to bow around the precipitate rather than shearing it.
Considering finely dispersed coherent
At the beginning of aging treatment, fine and uniform precipitation of
With increase in aging time, aspect ratio and number density of
The
Furthermore, the ductility (usually expressed in terms of elongation to fracture) of age-hardening Aluminum alloys also varies with aging time in accordance to the size, morphology and coherency of the strengthening precipitates [20, 21]. When the precipitates are small and coherent and their number density is low, dislocations can move past easily through them leading to maximum contribution from strain hardening that delays fracture. Correspondingly, under-aged alloy shows maximum ductility. On the other hand, semi-coherent and large strengthening precipitates at the peak aged condition renders maximum hindrance to the dislocation motion due to Orowan looping resulting in significant pile up at the precipitate sites. The ductility for the peak-aged alloy is also correspondingly minimum. With over-aging, some ductility is restored since the coarse, incoherent precipitates are generally not suitable to hinder dislocation motion and little pile up results around them. Overall, the ductility vs. aging time variation follows a reverse trend to the strength/hardness vs. aging time curves.
One of the major hindrances for widespread use of Al-Cu alloys, especially in the automobile and aerospace sectors, is their poor high temperature stability associated with rapid decrease in load bearing capacity above ∼250°C [22]. This strength degradation is because of the rapid coarsening of θ
At long thermal exposure,
Over the years, alloying pure Aluminum with various elements showed good promises for elevated temperature applications. Such elements included rare earths (e.g. Erbium, Ytterbium, Scandium etc.) as well as Zirconium, Silicon etc. [25, 26, 27]. For these alloys, formation of coherent precipitates with cubic L12 crystal structure and reduced interfacial energy is the key for their high temperature stability against precipitate coarsening upon thermal exposure [26]. The other unique exploration is the formation of core-shell structure for the strengthening precipitates which also provides excellent coarsening resistance through the minimization of interfacial energy. For example, addition of 0.06 at% Zr or 0.03 at% Er in Aluminum individually form ordered L12 Al3Zr or Al3Er precipitates and show moderate coarsening resistance at elevated temperature [25]. Simultaneous addition of Zr and Er in similar quantity however, leads to Al3(Er, Zr) precipitates with unique core shell structure, which made them coarsening resistant up to 400°C for 750 hours. The difference in diffusivity between Zr and Er was held responsible for formation of such core-shell structure; while Er having higher diffusivity forms the primary precipitate with Aluminum, slower diffusing Zr segregates later at the interfaces of these primary precipitates resulting in the core-shell structure. Similarly, addition of Sc to Al-Zr-Sc-Er alloy (concentrations of both Sc and Er are 0.06 at%) leads to a dual shell layer of Zr and Sc according to their respective diffusivity in Al matrix over the Al3Er core precipitate [26].
Furthermore, excellent creep resistance was observed for Al-0.1 at% Zr and Al-0.1 at% Zr-0.1 at% Ti alloy systems at 300°C, 350°C and 400°C, which is attributed to the high temperature stability of Al3Zr precipitates [28]. Out of the two alloys, ternary Al-Zr-Ti alloy showed comparatively lower creep resistance than binary Al-Zr alloy due to the lower lattice parameter mismatch between Al3(Zr1-xTix) core-shell precipitates with the parent α-Al matrix. The addition of Yb similarly resulted in excellent thermal stability for Al-0.9 at% Zr- 1.73 at% Yb alloys having Al3(Zr,Yb) precipitates up to 400–425°C [29].
For Al-Si system, Al-Si-Cu-Mg alloys are traditionally used for making high temperature pistons for automobile engines [30, 31]. These alloys show satisfactory microstructural stability as well as fatigue resistance at high temperatures which are essential requirements for automotive applications. A viable route for further improving their high temperature performance is by addition of transition metals that forms thermally stable intermetallic precipitates. For example, controlled Zr addition (up to 0.11 wt%) increases the ultimate tensile strength (UTS) of Al-Si-Zr piston alloys by 3.8% at 350°C due to the alteration in the morphology of strengthening ZrAlSi precipitates from flake to block shape [32, 33]. However, increase in Zr content up to 0.46 wt% resulted in a decrease in UTS by 5%. Similarly, A356 alloy (Al-7Si-0.4 Mg) modified with 0.25 wt% Er and nominal amount of Zr (0 to 0.6 wt%) showed improved high temperature mechanical properties [34]. With increase in Zr content up to 0.59 wt%, both hardness and tensile strength increases at room and elevated temperatures due to the formation of Al3(Er,Zr) precipitates.
Hypoeutectic Al-7 wt%Si-1wt%Cu-0.5 wt% Mg alloys also shows excellent retention of hardness and tensile strength up to 240–260°C when micro-alloyed with 0.15 wt% Zr, 0.28 wt% V and 0.18 wt% Ti [35]. Further exposure to 475°C upto 128 hours led to additional improvement in hardness which can be attributed to the accelerated precipitation of Al3(Zr,V,Ti) and Q′ precipitates. Similarly, addition of minor Ti (0.22 wt%), Zr (0.39 and 0.19 wt%) and Ni (0.46–0.21 wt%) to commercial 354 alloy showed improvement in tensile properties up to 300°C compared to the base alloy [36]. In both cases, micro-alloying elements synergistically result in unique and complex precipitate formation which improved the high temperature stability of the corresponding alloys. For hypereutectic Al-Si alloys, Ni addition up to 1–4 wt% to Al-12 wt%Si-0.9 wt% Cu-0.8 wt% Mg alloy resulted in retention of room temperature mechanical properties, including creep resistance up to 250°C due to the formation of thermally stable Al3Ni precipitates [37]. In addition to primary and eutectic Si, incorporation of 1 wt% ZnO nanoparticles (particle size ∼40 nm) also enhance the high temperature tensile strength and elongation for Al-20 wt% Si alloys [38].
In case of age hardening Al-Cu system, several attempts were made in the past to increase their high temperature stability by adopting various strategies. Lin et al. [39] studied the effect of Ni addition (0.5–1.5 wt%) on the elevated temperature mechanical properties of squeeze cast Al-Cu-Mn-Fe alloys. At 300°C, the amount of thermally stable precipitates (e.g. Al9FeNi, Al3CuNi and Al20Cu2Mn3) increases with increasing Ni content which enhances the elevated temperature mechanical properties of the base alloy. Addition of La in Al-Cu alloy similarly results in the formation of Al11La3 precipitates leading to a better high temperature mechanical properties with 0.3 wt% La being the optimized concentration [40]. The addition of 1.6–2.0 wt% Li also shows excellent mechanical properties for AA2099 (Al-Cu-Li) alloys at high temperature, primarily due to the enhanced thermal stability of T1 (Al2CuLi) precipitates compared to other possible strengthening precipitates like θ′ and S (Al2CuMg) [41]. At higher temperature, T1 precipitates coarsen instead of dissolving unlike θ′ or S. In addition, AA2219 alloy possesses improved high temperature performance when micro-alloyed with 0.8 wt% Sc, 0.45 wt% Mg and 0.2 wt% Zr from grain refinement and simultaneous precipitation of Al3Sc, Al3Zr and Ω precipitates along with other common strengthening precipitates like θ′ and θ″ [42].
Another viable strategy of increasing the thermal stability of Al-Cu alloys is by micro-alloying with various secondary elements for stabilization of strengthening metastable
Overall, there have been numerous efforts in the past to design high temperature Aluminum alloys from different binary systems (Al-Cu, Al-Si etc.), primarily by micro-alloying with various elements. However, most of these attempts showed certain shortcomings. The working temperature of the resultant ternary or quternary alloys could not be increased above 300°C under prolonged exposure. Also, use of exotic elements like rare earth additions hindered their industrial acceptance and commercial viability. Hence, the demand of cost-effective Aluminum alloys for high temperature applications has only increased over the years without much of a success.
As mentioned before, age hardening Al-Cu alloys faces significant precipitate coarsening, which restricts their use for high temperature applications [48]. Numerous attempts have made over the years to increase the operational temperature for Al-Cu alloys; the most successful approach was by trace addition of various elements like Sc and Zr [49]. Micro-alloying improves the high temperature stability in two distinct ways:
Micro alloying elements can provide heterogeneous nucleation sites for primary strengthening precipitates (e.g. θ
Micro alloying elements can segregate at the high energy mobile semi-coherent precipitate/matrix interfaces and at times, at the less-mobile coherent interfaces [52]. Such segregation eventually results in the reduction of energy for these interfaces, making them difficult to grow. The semi-coherent interfaces is usually more effected by such segregation [53, 54]. In recent times, stabilization of semi-coherent and coherent interfaces of strengthening θ
The classical approach for developing any new alloy system relies on the age-old trial and error method which has serious drawbacks, primarily considering the resource constrains and added cost from industrial standpoints [55, 56]. A more state of the art strategy of alloy designing is by using integrated computational materials engineering (ICME) approach [57, 58]; a successful example of this is realized in the development of Al-Cu-Mn-Zr alloys. The key components of ICME approach for the development of this alloy system are: (a) thermodynamic and kinetic approximations for stability of precipitates against growth controlling mechanism/s, (b) appropriate modeling for assessment of thermo-physical and thermo-mechanical properties from existing phases, (c) simulation and model/s to predict defect formation during casting processes, (d) models for prediction of microstructure during casting and other thermo-mechanical processing operations, (e) models for property prediction from microstructure and defect structure evolution, and (f) models for manufacturing of components at in-service conditions [59, 60].
These above mentioned steps were followed in the development of Al-Cu-Mn-Zr alloys which was primarily aimed to replace traditional Al-Si and Al-Si-Cu alloys in automotive applications (e.g. cylinder heads in passenger vehicle engines) [59]. Firstly, thermo-physical and thermo-mechanical properties for casting process simulation were obtained from thermodynamic databases. The simulation of casting process was conducted to estimate the casting defects and as-cast microstructure. Afterwards, thermodynamic models were employed for optimization of heat treatment cycle in terms of desired precipitation sequence, precipitate growth etc. This helped to estimate the spatial variation of thermo-physical properties over the component scale as well. Finally, component level properties e.g. residual stress, fatigue performance etc. were evaluated in order to estimate the in-service performance of the alloys considering the above mentioned parameters [61].
The primary mechanism for high temperature stability of Al-Cu-Mn-Zr alloys is related to the segregation of micro-alloying solute atoms (Mn and Zr) at θ′ precipitate/α-Al matrix interfaces [48, 52]. Although it seems fairly straight forward in the first go, the interface stabilization process exhibits extreme intricacies throughout the entire precipitation sequence. As denoted earlier, the primary strengthening precipitate in Al-Cu system is θ′, which has a plate shaped morphology where the broad facets are coherent with parent α-Al matrix (Figure 1c) [12]. The rim of the precipitates, on the other hand, are semi-coherent and have a higher interfacial energy compared to their coherent counterparts which makes them highly mobile and prone to coarsening [48].
On exposure to high temperature for an extended duration, θ′ precipitates coarsen due to the enhanced diffusion of solute Cu atoms [8]. Segregation of Mn and Zr atoms at the θ′ precipitate/α-Al matrix interfaces prohibits Cu diffusion and further coarsening at elevated temperature [48]. The main driving force behind the solute segregation is the reduction of precipitate/matrix interfacial energy, especially for the semi-coherent interfaces. In addition, several other mechanisms like solute drag, ledge poisoning etc. also helps in the stabilization of θ′ precipitates [52, 62]. These mechanisms are explained individually below.
In the earliest report on Al-Cu-Mn-Zr alloys, Shyam et al. [48] compared two cast Al-Cu-Mn-Zr alloys having nominal compositions Al-5Cu-1.5Ni-0.2Mn-0.17Zr and Al-6.4Cu-0.19Mn-0.13Zr (in wt%) with conventional Al-Cu (206) and Al-Si-Cu (319) i.e. with non- Al-Cu-Mn-Zr alloys containing negligible concentration of Zr (Figure 3). At room temperature, base Al-Cu and Al-Si-Cu alloys exhibit superior mechanical response (higher yield strength and ductility) than Al-Cu-Mn-Zr alloys. However, the trend completely reverses after treating the alloys at higher temperature (300°C) for 200 hours; Al-Cu-Mn-Zr alloys now represent superordinate mechanical response than either Al-Cu or Al-Si-Cu alloys. Microstructural examinations reveal that θ′ precipitates significantly coarsen and transform to thermodynamically stable θ precipitates for base Al-Cu or Al-Si-Cu (i.e. non Al-Cu-Mn-Zr) alloys because of which their mechanical properties degraded after thermal treatment. On the other hand, θ′ precipitates retain their morphology and aspect ratio on high temperature heat treatment in case of Al-Cu-Mn-Zr alloys.
(a) and (b) showing the microstructures of Al-Cu-Mn-Zr alloy in peak aged condition and post 300°C thermal exposure for 200 hours, respectively; (c) and (d) represents true-stress-true strain curves for these alloys from tensile tests carried out at room temperature and 300°C, respectively; (e) and (f) showing the microstructures for conventional Al-Si-Cu alloy under similar conditions [
Bahl et al. [52] further studied the aging kinetics and thermal stability of Al-Cu-Mn-Zr alloys and showed that they retained their room temperature mechanical properties even after exposure at 300°C for 5000 hours. During such prolonged thermal treatment, θ′ precipitates suffer limited decrease in number density up to 200 hours. No further significant decrease was observed, and the peak-aged microstructure remains fairly stable up to 5000 hours.
The stability of θ′ precipitates in Al-Cu-Mn-Zr alloy was examined using atom probe tomography (APT) characterization which are shown in Figures 4a and b (side view and top view, respectively) [48, 62]. Figure 4c represents corresponding composition profile which indicates segregation of Cu, Mn, Zr and Si at the coherent and semi-coherent θ′ precipitate/α-Al matrix interfaces for Al-Cu-Mn-Zr alloys after prolonged (200 hours) thermal exposure at 300°C. As it appears, Mn tends to segregate both at the coherent and semi-coherent interfaces of θ′ precipitates with the segregation tendency being larger at the later interfaces. Zr, on the other hand, segregates more on the corner rim of the coherent/semi-coherent interfaces, although certain extent of Zr segregation also occurs on these interfaces. Silicon have similar segregation profile as Mn; it can in fact influences the solute segregation at these interfaces to a much greater extent as discussed later [63].
(a) and (b) APT compositional maps (iso-concentration surfaces) representing side and top views, respectively of APT needle for Al-Cu-Mn-Ni-Zr alloy pre-conditioned at 300°C for 200 hours, (c) and (d) showing 2D contour plots for Cu, Si, Zr and Mn atoms on the cross-sectional planes of
In order to understand the individual and synergistic effect of Mn and Zr micro-alloying on the thermal stability of Al-Cu-Mn-Zr alloy, a consolidated study was carried out by Poplawsky et al. [62] on several model alloys (e.g. Al-Cu-Mn, ACM and Al-Cu-Zr, ACZ etc.) in addition to the base Al-Cu-Mn-Zr alloy. The Al-Cu-Mn alloys retain their room temperature mechanical strength after exposure at 300°C for 200 hours whereas Al-Cu-Zr alloys could sustain their stability only up to 200°C. For comparison, Al-Cu-Mn-Zr alloys are stable up to 350°C. The trend in Mn segregation for Al-Cu-Mn-Zr alloy in this case is similar to that observed earlier by Shyam et al. [48] up to 300°C. Larger Mn segregation occurs at semi-coherent interfaces while minor segregation at the coherent interfaces.
After thermal exposure at 350°C, Mn segregation at semi-coherent interfaces becomes insignificant, which aggravates the mechanical degradation of Al-Cu-Mn alloys at this temperature range [62]. At 350°C, Mn tends to diffuse within the bulk of θ′ precipitates, thereby causing even lesser segregation at the semi-coherent interfaces. Zr, on the other hand, retains their segregation profile at the coherent interfaces up to 200°C for Al-Cu-Zr alloys. The Zr segregation profile is also similar in nature to that observed previously for Al-Cu-Mn-Zr alloys by Shyam et al. [48].
Solid state diffusion is one of the key component for evolution of precipitate structure and morphology during the course of thermal exposure [64]. In the corresponding binary systems, self-diffusion coefficient of Cu is much higher than that for Mn so that diffusion of Cu atoms continue to coarsen
Due to this sequence of segregation (initial segregation of Mn followed by Zr segregation on prolonged thermal exposure),
The diffusion aided coarsening of θ′ precipitates can be best described using the classic Lifshitz-Slyozov-Wagner (LSW) theory [67] where the rate of coarsening depends on the corresponding mass transfer mechanism (lattice diffusion, interface atomic mobility, grain boundary diffusion, pipe diffusion through dislocation cores etc.). The governing equation in LSW theory is given as [68]:
where,
Since
Furthermore, the constant
As it seems, the microstructural requirement for better coarsening resistance and high temperature stability of Al-Cu-Mn-Zr alloy is quite counterintuitive. At room temperature, a fine-scale microstructure with smaller precipitates and correspondingly, smaller inter precipitate spacing is preferred for high strength [8]. However, a larger precipitate with higher inter-precipitate spacing is desired for enhanced coarsening resistance at higher temperature. Together, Al-Cu-Mn-Zr alloys present low to moderate strength at room temperature but excellent retention of that strength at elevated temperature [48].
Other than the major micro-alloying elements (Mn & Zr), trace elements (e.g. Si and Ti) present in the composition may further influence the microstructural stability of Al-Cu-Mn-Zr alloy at elevated temperature. Silicon decreases the coarsening resistance for
After solution treatment of Al-Cu alloys, quench-in vacancies can cluster together to form edge dislocations at room temperature [12, 69]. When these vacancies are in significant density, they can even form dislocation loops rather than individual dislocations, which can further climb and form dislocation helices [70, 71, 72, 73, 74]. These helices accommodate far more number of vacancies with their spacings being larger than individual dislocations. When Si atoms are present in significant quantity in the binary Al-Cu alloy, they can also cluster together during aging due to high diffusivity. The dislocations, dislocation helices and Si clusters can all potentially provide heterogeneous nucleation sites for θ′ precipitates when aged above θ″ solvus.
When the Si content is kept low (<0.05 wt%), Al-Cu alloys essentially act as a binary system and θ′ precipitates mostly nucleate at the dislocation loops, thereby promoting a fine scale microstructure on aging [63]. At higher Si content (0.11 wt%-0.24 wt%), θ′ precipitates nucleate at Si clusters, which again leads to a finer microstructure. However, at the intermediate Si content (0.05–0.1 wt%), nucleation of θ′ precipitates primarily occurs at the dislocation helices. As a result, the number density of θ′ precipitates decreases such that their inter-precipitate spacings become larger as well as the critical size for
Titanium when present in trace concentration can also influence the high temperature stability of Al-Cu-Mn-Zr alloys by forming stable Al3Ti precipitates having L12 crystal structure [75]. Titanium atoms show similar segregation profile as Zr at θ′ precipitate/α-Al matrix interfaces. Poplawsky et al. [62] in this regard observed unique L12 structured Al3(ZrxTi1-x) precipitates on the α-Al matrix/ θ′ precipitate interfaces from addition of Ti to Al-Cu-Mn-Zr alloys. The (001) interfaces of this Al3(ZrxTi1-x) precipitates are coherent with
Furthermore, self-diffusion coefficients of Mn, Zr and Ti in Al vary in the order
Schematics showing (a) segregation of Mn at the semi-coherent interface of
As discussed before, reduction in interfacial energy due to the segregation of solute atoms (Mn and Zr) at the mobile interfaces promotes thermal stabilization for metastable θ′ precipitates up to a prolonged duration [48]. In this regard, density functional theory (DFT) simulations were carried out to determine the interfacial energy for various θ′ precipitate/α-Al matrix interfaces with and without solute addition (Mn & Zr). In DFT calculations, segregation energy
where,
where,
Important to note that the coarsening of strengthening precipitates is
Introduction of a third element (Mn, Zr etc.) within the binary Al-Cu alloys can lead to one or a combination of thermodynamic and kinetic restrictions (mentioned above) to precipitate coarsening processes. Shower et al. [76] in this regard carried out a phase field modeling study to understand the synergistic effect of various mechanisms that offers precipitate coarsening resistance. The study suggests that a combination of interfacial energy reduction and solute drag due to the addition of Mn and Zr contributes to the coarsening resistance of θ′ precipitates up to 300°C. In the process, a continuous segregation profile forms for Mn atoms along the interfaces of θ′ precipitates with a larger weightage at the semi-coherent interface. Other solute atoms e.g. Zr, which introduce a positive misfit strain do not effectively interact with the mobile semi-coherent interfaces; rather they tend to segregate at the coherent interfaces. When the working temperature is raised to 400°C, resistance to precipitate coarsening requires simultaneous reduction in the mobility of Cu atoms through α-Al matrix and the interfacial energy of θ′ precipitates. This could not be achieved by micro-alloying with Mn and Zr alone, which is why the Al-Cu-Mn-Zr alloys losse their excellent thermal stability at 400°C and beyond. All the cumulative and inter-connected effects that contribute to the stabilization of θ\' precipitate at elevated temperature in Al-Cu-Mn-Zr alloy are schematically shown in Figure 6.
Schematic flowchart showing the cumulative effect of various contributing factors and mechanisms involved in the stabilization of
Similar to other age hardening Al-Cu alloys, primary strengthening mechanism for peak-aged Al-Cu-Mn-Zr alloys is Orowan looping where matrix dislocations bow around the coarse θ′ precipitates [52]. Apart from this, solid solution and grain boundary strengthening (by Hall–Petch mechanism) also contributes to the overall strength of the Al-Cu-Mn-Zr alloys. Analytical calculations, however, suggest that Orowan looping plus other strengthening mechanisms together are inadequate to account for experimentally measured yield strength of Al-Cu-Mn-Zr alloys [52]. This calls for the consideration of additional strengthening mechanisms e.g. stress-free transformation strain (SFTS). The formation of θ′ precipitates in the α-Al matrix is usually associated with transformation strain fields which can interact and potentially restricts dislocation movement, thereby increasing the alloy strength further.
Figures 3c–d indicates that the room temperature tensile properties for peak aged Al-Cu-Mn-Zr alloy is inferior compared to the conventional peak-aged Al-Cu alloy. For example, the ultimate tensile strength(UTS) of Al-5Cu alloy is ∼490 MPa whereas it is ∼300 MPa for Al-Cu-Mn-Zr alloy at room temperature [48]. In addition, the yield strength of the later alloy is nearly half compared to the base Al-Cu alloy. However, after prolonged thermal exposure at 300°C, the trend reverses; Al-Cu-Mn-Zr alloy possess nearly twice the UTS and yield strength compared to the base Al-Cu alloy. Similarly, Al-5Cu-Mg alloy possess higher hardness than Al-Cu-Mn-Zr alloys at room temperature (Figure 7). With increase in pre-conditioning temperatures (heat treatment for 200 hours), non- Al-Cu-Mn-Zr alloys show drastic decrease in hardness around 200°C, while Al-Cu-Mn-Zr alloys can sustain the room temperature hardness without any significant degradation until 350°C.
Room temperature hardness for various conventional Al-Cu and Al-Cu-Mn-Zr alloys as a function of pre-conditioning temperatures [
Bahl. et al. [52] further showed that the hardness and yield strength of peak-aged Al-Cu-Mn-Zr alloy drop marginally during post-aging thermal exposure but remained almost constant during prolonged thermal treatment up to 5000 hours. This accounts for a stable microstructure with almost constant precipitate volume fraction, thickness, diameter, aspect ratio, equivalent diameter, number density and inter-precipitate spacing for Al-Cu-Mn-Zr alloys on extended thermal exposure. The ductility of Al-Cu-Mn-Zr alloys are further influenced from Cu content although it does not vary the yield strength and UTS much. For example, increasing the Cu content from 6 wt% to 9 wt% causes the fracture strain to reduce by 50% primarily due to the increased amount of brittle intermetallics at α-Al matrix grain boundaries [80].
Important to note that no comprehensive study is yet to report the results pertaining to full-scale tensile testing, especially the strain hardening response as well as the fracture characteristics of Al-Cu-Mn-Zr alloys whether at room or elevated temperatures. The earliest available work of Shyam et al. [48] showed certain true stress–strain curves for Al-Cu-Mn-Zr alloy from tensile tests carried out at room temperature and 300°C in comparison to regular Al-Cu alloy (Figure 3). The purpose of the tensile tests was however, to establish the superiority for the former alloy at elevated temperature. Important to note that the alloys (Al-Cu and Al-Cu-Mn-Zr alloys) were used in peak-aged condition for room temperature tensile tests and after pre-conditioning at 300°C for 200 hours for elevated temperature tests.
The true stress–strain curves from room temperature tensile tests suggest that peak-aged Al-Cu-Mn-Zr alloy possesses marginally higher strain hardening rate compared to the conventional Al-5Cu-Mg alloy at least in the initial part of the plastic regime. The hardening rates although do not vary much at the later part (below UTS) representing almost similar slopes for both alloys. During 300°C tensile tests, both Al-Cu-Mn-Zr and Al-5Cu-Mg alloys exhibit substantial strain softening, however at significantly differing rates; the rate of softening is greater for Al-Cu-Mn Zr alloy compared to the conventional Al-Cu-Mg alloy. The ductility for the former alloy is also always higher than the later alloy irrespective of the test temperature. The strain hardening response for precipitate hardened systems at room temperature is generally attributed to the isotropic hardening of α-Al matrix plus kinematic hardening due to dislocation pile up at the precipitate locations from continued Orowan looping [81, 82, 83]. The strain softening at elevated temperature can possibly be attributed to dynamic recovery of piled-up dislocations which reduces dislocation density at precipitate cites and increases ductility by delaying the final fracture.
The excellent high temperature stability of Al-Cu-Mn-Zr alloys enhances their creep properties as well. Miligan et al. [84] conducted creep tests under different stress levels for various Al-Cu-Mn-Zr alloys with varying grain sizes at 300°C and compared their creep resistance with base Al-Cu alloy as well as Al-Sc alloy which is known for its excellent creep resistance. Figure 8 represents the steady state creep strain rate as a function of applied stress for these alloys. At low stress level, stress exponents for Al-Cu-Mn-Zr alloys are close to unity signifying for diffusional creep being the dominant mechanism. On the other hand, dislocation creep is the mechanism for conventional Al-Cu alloy as identified from a higher stress exponent. The dislocation movement though α-Al grain interiors is difficult at low stress levels for Al-Cu-Mn-Zr alloys due to the enhanced thermal stability of θ′ precipitates; rather grain boundary diffusion dominates at high temperature making diffusional Coble creep as the rate controlling mechanism. At higher stress levels however, the controlling mechanism switches to dislocation creep even for Al-Cu-Mn-Zr alloys since the grain boundary precipitates effectively slow down the movement of vacancies. This in turn restricts grain boundary diffusion as well as grain boundary sliding.
Creep curves showing the steady state creep strain rate as a function of applied stress for various Al-Cu-Mn-Zr alloys (RR350, Al-7Cu SG and Al-7Cu LG where SG and LG refers to small and large grains, respectively) plus base Al-Cu and Al-Sc alloys [
One of the prime motivations for the development of Al-Cu-Mn-Zr alloy is to replace conventional cast Aluminum alloys (e.g. Al-Si-Cu based 319 alloy) for making light weight components in automotive engines [48, 85]. The Al-Cu-Ni based RR350 alloy with 0.2 wt% Mn and 0.17 wt% Zr, which can be considered as a variant of Al-Cu-Mn-Zr alloys, is also used as light weight and high temperature resistant alloys for high end automobile engine applications over the years [86]. Shower et al. [87] has compared the effect of microstructural stability on the high temperature deformation response of RR350 alloy vis-à-vis 319 alloy in as-cast condition by conducting isothermal hot compression tests at different temperature-true strain rate combinations. At all strain rates, compressive flow stress of 319 alloy is greater than that for RR350 alloy up to 200°C (Figure 9a). However, within 250–300°C, RR350 alloy possesses higher flow stress which can be attributed to the stability of strengthening θ′ precipitates. In this temperature range, 319 alloy losses its flow stress by 40%. At lower strain rates (e.g. 10−4 s−1 & 10−3 s−1), primary deformation mechanism for both alloys is strain hardening at room temperature, which changes to dynamic recovery and cross slip of dislocation at 250°C. Afterwards, dynamic recrystallization becomes predominant at 300°C while grain boundary sliding is the primary deformation mechanism at 350°C. In addition, RR350 alloy shows formation of shear bands as well as bending of θ′ precipitates within α-Al grains having <100> direction nearly parallel to the compression axis in the microstructure of specimens deformed at 300°C (Figure 9b).
(a) Comparison of flow stress variations with test temperatures for 319 and RR350 alloys at different strain rates, and (b) post-compression (at 300°C and 1 s−1 strain rate) SEM micrograph of RR350 alloy showing shear band formation and bending of θ′ precipitates within α-Al grains having <100> direction nearly parallel to the compression axis [
The excellent high temperature stability of Al-Cu-Mn-Zr alloys also make them a prime candidate for fracture critical engineering applications where fatigue properties are crucial consideration. Bahl et al. [88] studied the effect of Cu concentration on the high temperature (250°C) low cycle fatigue (LCF) properties of Al-Cu-Mn-Zr alloys that led to a correlation between LCF life and monotonic tensile fracture strain. At low strain amplitude (0.1%), Al-Cu-Mn-Zr alloys with either 6 wt% or 9 wt% of Cu do not undergo failure even after 105 number of cycles. However, at higher strain amplitudes (0.2% and 0.3%), the alloys fail within these many cycles of testing. This suggests that the fatigue life of Al-Cu-Mn-Zr alloys decreases with increasing strain amplitude.
For the peak-aged Al-Cu-Mn-Zr alloys with varying Cu content that underwent a further thermal exposure at 250°C for 100 hours, initiation of fatigue cracks almost always occur from the surface pores rather than from coarse grain boundary precipitates [80]. The fracture surfaces correspondingly do not contain much of the traces of intermetallic precipitates. Finite element modeling (FEM) also indicates that stress concentration at the pores are higher compared to that at the grain boundary precipitates. The low strain amplitude in the fatigue testing possibly led to the pore assisted crack initiation since otherwise the cracking from grain boundary precipitates would require higher stress concentration and their decohesion from the matrix which is only possible at larger strains [88].
Furthermore, since the variation in Cu content only affects the volume fraction of grain boundary intermetallic precipitates, it does not influence the cracking and in turn, low cycle fatigue behavior of Al-Cu-Mn-Zr alloys [80]. The thermal stability of θ′ precipitates also does not influence the fatigue property of these alloys since both crack initiation and propagation occur at a larger microstructural scale (from surface pores). It therefore appears that controlling the casting defects (predominantly shrinkage pores) is the most crucial factor to enhance the LCF life for Al-Cu-Mn-Zr alloys. Overall, these alloys exhibited moderate to excellent high temperature low cycle fatigue life making them suitable for components meant for elevated temperature applications.
Industrial application of Al-Cu-Mn-Zr alloys require certain additional considerations on and above their excellent thermal stability and associated improvement in most of the high temperature mechanical properties as mentioned above. These include, but certainly not restricted to the ease of casting and defect formation, assessment of mechanical properties e.g. fatigue testing at larger component scale, possibility to adopt alternate component fabrication methodologies like additive manufacturing, wrought processing etc. [89]. Some of these aspects are mentioned below:
Hot tearing is a crucial casting defect that can affect the structural stability and properties of as-cast components [90, 91]. During solidification, molten metal usually remains in semi-solid state (mushy zone) for considerable duration. It also undergoes severe volume contraction and associated thermal stresses within the semi-solid metal regions. Under this condition, cracks form in the solidified component if there is an inadequate supply of molten mass to fill up the shrinkage volume. Controlling such defects in castings is difficult but extremely important for improving the fatigue life per se [91].
Sabau et al. [92] studied the hot tearing resistance of cast Al-Cu-Mn-Zr alloys with and without grain refiners in comparison to base Al-Cu and Al-Si alloys. The base Al-Cu alloy with >7 wt% Cu exhibits a grain refined microstructure in the casting. It also shows a decrease in the length of columnar to equiaxed transition zone that in turn improves the hot tearing resistance. In addition, simultaneous presence of Si and Fe (>0.2 wt%) increases the hot tearing resistance for this alloy. The low Cu containing alloys, on the other hand, possess coarse columnar grains within the cast microstructures which facilitates hot tearing for them. For the Al-Cu-Mn-Zr alloys, when Cu is added above 7 wt%, significant grain refinement occurs which further contributes to their excellent hot tearing resistance. In addition, when 0.1 wt% Ti is added as additional grain refiner, resultant Al-Cu-Mn-Zr alloy exhibits the finest microstructure and correspondingly, the best hot tearing resistance [89]. Ti added Al-Cu-Mn-Zr alloy was therefore speculated suitable for industrial applications [92].
In the measurement of hot tearing resistance, Sabau et al. [92] used an in-house multi-arm casting setup with varying arm length in a permanent mold. In this six-armed mold, the shortest arms were free from any visible cracks for all the alloys having varying amount of Cu and Ti, while the longest arm had severe cracking for these alloys. As per the visible inspection, a cracking index (
The length of the arms, however, also plays a crucial role in the formation of these cracks. The longer arms are more susceptible to cracking compared to the shorter ones so that the weighted average was preferred for the calculation of HTI. The weighted average
where,
Alloy | Ti content (wt%) | |
---|---|---|
Al-Cu-Mn-Zr with 8 wt% Cu | 0.02 | 2.6 |
0.1 | 2.01 | |
0.2 | 2.36 | |
Al-Cu-Mn-Zr with 6.2 wt% Cu | 0.1 | 2.6 |
0.2 | 3.21 | |
Al-Cu-Mn-Zr with 7.3 wt% Cu | 0.1 | 2.49 |
0.2 | 2.84 |
Hot tearing index (HTI) of different Al-Cu-Mn-Zr alloys with varying Ti content.
In recent times, additive manufacturing (AM) is proven to be an extremely useful and alternate technique for shaping intricate parts in industrially relevant scales with excellent property combinations compared to cast counterparts [93]. For Al alloys however, additive manufacturing is a rather complicated and challenging process due to several factors like poor powder flowability, high thermal conductivity, laser reflectivity etc. [94]. In this regard, Shyam et al. [95] successfully fabricated AM parts from Al-Cu-Mn-Zr alloys by selective laser melting (SLM) without any hot tearing using optimized processing parameters. The substrate temperature for SLM was kept 200°C which was sufficient for in-situ formation of strengthening θ′ precipitates.
Due to laser melting, AM Al-Cu-Mn-Zr alloys form typical “peacock tail” microstructure having overlapping melt pools. In addition, the AM microstructure consists of long columnar grains at the top and fine equiaxed grains at the bottom of the melt pools. Such refined AM microstructure yields comparatively higher strength up to 300°C compared to the cast Al-Cu-Mn-Zr alloys. The bimodal grain size distribution and refined grain boundary intermetallic precipitates further enhance the tensile elongation for AM Al-Cu-Mn-Zr alloys. However, creep properties for these AM alloys are somewhat compromised compared to the cast counterparts due to high proportion of grain boundaries in the refined AM microstructure. Overall, AM Al-Cu-Mn-Zr alloys are envisioned having potential in complex component manufacturing for high temperature applications owing to the simultaneous positive effects of refined microstructure and in situ formation of thermally stable strengthening θ′ precipitates [95].
In the current global scenario, any new alloy development must help in reducing environmental impact e.g. carbon footprint and green house emissions [96]. The primary target area for Al-Cu-Mn-Zr alloys is automotive industry, which also formed the early motivation of their inception and further development [97]. The aim was to develop Al alloys for engine components that experience high working temperature (∼300°C) e.g. cylinder heads in combustion engines. The use of Al-Cu-Mn-Zr alloys for making such components can effectively raise the working temperature and increase the fuel efficiency of next generation passenger vehicles, thereby proving environment friendly in terms of fuel consumption.
The present book chapter elucidates a comprehensive review about the development as well as the science and technology behind the new-age Al-Cu-Mn-Zr (ACMZ) alloys. The major observations are summarized below.
The new age Al-Cu-Mn-Zr (ACMZ) alloy developed in recent times by micro-alloying conventional Al-Cu alloys with Mn and Zr shows unprecedented microstructural stability up to ∼350°C.
The strengthening θ′ precipitates in Al-Cu-Mn-Zr alloys are stabilized primarily due to preferential solute segregation (Mn & Zr) at the θ′ precipitate/α-Al matrix interfaces which helps in reducing their interfacial energy. Mn atoms segregate at the mobile semi-coherent interfaces while Zr atoms primarily sits at the corner of coherent/semi-coherent interfaces.
The difference in the diffusivity of micro-alloying elements decides the sequence of their segregation at θ′ precipitate/α-Al matrix interfaces. This in turn plays a synergistic role in stabilizing θ′ precipitate at different temperature ranges. Faster diffusing Mn initially segregates at both coherent and semi-coherent interfaces and provides thermal stability at lower temperatures. Zr being relatively slower diffusing element segregates at a later stage but effectively restricts
Various other mechanisms e.g. solute drag, diffusion barrier formation, ledge poisoning by co-precipitation of thermally stable intermetallics etc. also contributes to the coarsening resistance of
Trace elements like Ti and Si further influence θ′ precipitate stability in Al-Cu-Mn-Zr alloys. Si above a critical content (>0.1 wt%) potentially substitutes Mn and Zr at the θ′ precipitate/α-Al matrix interfaces, thereby decreasing the stability of
DFT simulations confirm the reduction of interfacial energy from segregation of micro-alloying elements and provide the segregation profiles at various (coherent and semi-coherent) interfaces. Phase field simulations further suggest that the cumulative effect of interfacial energy reduction and solute drag led to the θ′ precipitate stabilization at 300°C. At 400°C, reduction in the mobility of Cu atoms is required in addition to reduced interfacial energy for efficient resistance towards θ′ precipitate coarsening.
As a result of the excellent thermal stability of strengthening
At high temperature (300–350°C), compressive flow stress of Al-Cu-Mn-Zr alloy (RR350) is higher than conventional Al-Si-Cu (319) alloy. The high temperature deformation mechanisms for the former alloy vary from strain hardening at room temperature to cross slip and dynamic recovery as the test temperature increases at 250°C. Further higher test temperature promotes dynamic recrystallization of the matrix at 300°C and finally lead to grain boundary sliding to 350°C.
The Al-Cu-Mn-Zr alloy shows excellent creep resistance compared to the base Al-Cu alloys. For the former alloy, diffusional Coble creep is the controlling mechanism at low stress levels which switches to dislocation creep at higher stress levels.
In high temperature low cycle fatigue testing, Al-Cu-Mn-Zr alloy does not fail up to 105 cycles at low stress amplitudes whereas the fatigue life decreases with increasing stress amplitude. The casting defects (pores) are found to be more influential factor by means of stress concentration and crack initiation than either the stability of
The Al-Cu-Mn-Zr alloy exhibits superior hot tearing resistance compared to the conventional Al-Cu alloys. Additive manufacturing of Al-Cu-Mn-Zr alloy also shows promising property combinations owing to a refined microstructure and in-situ formation of strengthening
Overall, Al-Cu-Mn-Zr alloys offer huge potential for industrial applications where lightweight materials are sought after for excellent high temperature mechanical properties. These new-age alloys can in fact prove to be a game changer for the existing passenger vehicle engines and may bring a paradigm shift in the automobile sectors. Owing to low density and excellent high temperature stability, their future use is certainly leading to a safer and greener environment.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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It is a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants; which also regulates cell division and growth, is involved in signal transduction, and has roles in several physiological processes, such as immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption, has also roles in detoxifying the body of heavy metals. Severe deficiency of vitamin C causes scurvy, whereas limited vitamin C intake causes symptoms, such as increased susceptibility to infections, loosening of teeth, dryness of the mouth and eyes, loss of hair, dry itchy skin, fatigue, and insomnia. In contrast, vitamin C can also act as a prooxidant, especially in the presence of transition metals, such as iron and copper, starting different hazardous radical reactions. Vitamin C can both act as a strong, efficient, and cheap antioxidant agent and, at the same time, behave as a radical promoter. Further investigations are needed to illuminate the dual roles of vitamin C",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Fadime Eryılmaz Pehlivan",authors:[{id:"200567",title:"Dr.",name:"Fadime",middleName:null,surname:"Eryılmaz Pehlivan",slug:"fadime-eryilmaz-pehlivan",fullName:"Fadime Eryılmaz Pehlivan"}]},{id:"56440",doi:"10.5772/intechopen.70162",title:"Vitamin C: Sources, Functions, Sensing and Analysis",slug:"vitamin-c-sources-functions-sensing-and-analysis",totalDownloads:6438,totalCrossrefCites:15,totalDimensionsCites:28,abstract:"Vitamin C is a water-soluble compound found in living organisms. It is an essential nutrient for various metabolism in our body and also serves as a reagent for the preparation of many materials in the pharmaceutical and food industry. In this perspective, this chapter can develop interest and curiosity among all practicing scientists and technologists by expounding the details of its sources, chemistry, multifunctional properties and applications.",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Sudha J. Devaki and Reshma Lali Raveendran",authors:[{id:"187911",title:"Associate Prof.",name:"Sudha",middleName:null,surname:"J Devaki",slug:"sudha-j-devaki",fullName:"Sudha J Devaki"},{id:"204937",title:"Mrs.",name:"Reshma",middleName:null,surname:"Laly Ravindran",slug:"reshma-laly-ravindran",fullName:"Reshma Laly Ravindran"}]},{id:"50921",doi:"10.5772/63712",title:"Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet",slug:"menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet",totalDownloads:3328,totalCrossrefCites:10,totalDimensionsCites:21,abstract:"Vitamin K2 is a collection of isoprenologues that mostly originate from bacterial synthesis, also called menaquinones (MKs). Multiple bacterial species used as starter cultures for food fermentation are known to synthesize MK. Therefore, fermented food is the best source of vitamin K2. In the Western diet, dairy products are one of the best known and most commonly consumed group of fermented products.",book:{id:"5169",slug:"vitamin-k2-vital-for-health-and-wellbeing",title:"Vitamin K2",fullTitle:"Vitamin K2 - Vital for Health and Wellbeing"},signatures:"Barbara Walther and Magali Chollet",authors:[{id:"184784",title:"Dr.",name:"Barbara",middleName:null,surname:"Walther",slug:"barbara-walther",fullName:"Barbara Walther"},{id:"188194",title:"Mrs.",name:"Magali",middleName:null,surname:"Chollet",slug:"magali-chollet",fullName:"Magali Chollet"}]},{id:"66098",doi:"10.5772/intechopen.84445",title:"Golden Rice: To Combat Vitamin A Deficiency for Public Health",slug:"golden-rice-to-combat-vitamin-a-deficiency-for-public-health",totalDownloads:3386,totalCrossrefCites:12,totalDimensionsCites:17,abstract:"Vitamin A deficiency (VAD) has been recognised as a significant public health problem continuously for more than 30 years, despite current interventions. The problem is particularly severe in populations where rice is the staple food and diversity of diet is limited, as white rice contains no micronutrients. Golden Rice is a public-sector product designed as an additional intervention for VAD. There will be no charge for the nutritional trait, which has been donated by its inventors for use in public-sector rice varieties to assist the resource poor, and no limitations on what small farmers can do with the crop—saving and replanting seed, selling seed and selling grain are all possible. Because Golden Rice had to be created by introducing two new genes—one from maize and the other from a very commonly ingested soil bacterium—it has taken a long time to get from the laboratory to the field. Now it has been formally registered as safe as food, feed, or in processed form by four industrialised counties, and applications are pending in developing countries. The data are summarised here, and criticisms addressed, for a public health professional audience: is it needed, will it work, is it safe and is it economic? Adoption of Golden Rice, the next step after in-country registration, requires strategic and tactical cooperation across professions, non-governmental organisations (NGOs) and government departments often not used to working together. Public health professionals need to play a prominent role.",book:{id:"7978",slug:"vitamin-a",title:"Vitamin A",fullTitle:"Vitamin A"},signatures:"Adrian Dubock",authors:[{id:"273220",title:"Ph.D.",name:"Adrian",middleName:null,surname:"Dubock",slug:"adrian-dubock",fullName:"Adrian Dubock"}]},{id:"62836",doi:"10.5772/intechopen.79350",title:"The Role of Thiamine in Plants and Current Perspectives in Crop Improvement",slug:"the-role-of-thiamine-in-plants-and-current-perspectives-in-crop-improvement",totalDownloads:1566,totalCrossrefCites:7,totalDimensionsCites:11,abstract:"Current research is focusing on selecting potential genes that can alleviate stress and produce disease-tolerant crop variety. The novel paradigm is to investigate the potential of thiamine as a crop protection molecule in plants. Thiamine or vitamin B1 is important for primary metabolism for all living organisms. The active form, thiamine pyrophosphate (TPP), is a cofactor for the enzymes involved in the synthesis of amino acids, tricarboxylic acid cycle and pentose phosphate pathway. Recently, thiamine is shown to have a role in the processes underlying protection of plants against biotic and abiotic stresses. The aim of this chapter is to review the role of thiamine in plant growth and disease protection and also to highlight that TPP and its intermediates are involved in management of stress. The perspectives on its potential for manipulating the biosynthesis pathway in crop improvement will also be discussed.",book:{id:"6709",slug:"b-group-vitamins-current-uses-and-perspectives",title:"B Group Vitamins",fullTitle:"B Group Vitamins - Current Uses and Perspectives"},signatures:"Atiqah Subki, Aisamuddin Ardi Zainal Abidin and Zetty Norhana\nBalia Yusof",authors:[{id:"240031",title:"Dr.",name:"Zetty-Norhana Balia",middleName:null,surname:"Yusof",slug:"zetty-norhana-balia-yusof",fullName:"Zetty-Norhana Balia Yusof"},{id:"261167",title:"Mr.",name:"Aisamuddin Ardi",middleName:null,surname:"Zainal Abidin",slug:"aisamuddin-ardi-zainal-abidin",fullName:"Aisamuddin Ardi Zainal Abidin"},{id:"261169",title:"Ms.",name:"Atiqah",middleName:null,surname:"Subki",slug:"atiqah-subki",fullName:"Atiqah Subki"}]}],mostDownloadedChaptersLast30Days:[{id:"56440",title:"Vitamin C: Sources, Functions, Sensing and Analysis",slug:"vitamin-c-sources-functions-sensing-and-analysis",totalDownloads:6429,totalCrossrefCites:15,totalDimensionsCites:28,abstract:"Vitamin C is a water-soluble compound found in living organisms. It is an essential nutrient for various metabolism in our body and also serves as a reagent for the preparation of many materials in the pharmaceutical and food industry. In this perspective, this chapter can develop interest and curiosity among all practicing scientists and technologists by expounding the details of its sources, chemistry, multifunctional properties and applications.",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Sudha J. Devaki and Reshma Lali Raveendran",authors:[{id:"187911",title:"Associate Prof.",name:"Sudha",middleName:null,surname:"J Devaki",slug:"sudha-j-devaki",fullName:"Sudha J Devaki"},{id:"204937",title:"Mrs.",name:"Reshma",middleName:null,surname:"Laly Ravindran",slug:"reshma-laly-ravindran",fullName:"Reshma Laly Ravindran"}]},{id:"56013",title:"Vitamin C: An Antioxidant Agent",slug:"vitamin-c-an-antioxidant-agent",totalDownloads:7817,totalCrossrefCites:27,totalDimensionsCites:60,abstract:"Vitamin C or ascorbic acid (AsA) is a naturally occurring organic compound with antioxidant properties, found in both animals and plants. It functions as a redox buffer which can reduce, and thereby neutralize, reactive oxygen species. It is a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants; which also regulates cell division and growth, is involved in signal transduction, and has roles in several physiological processes, such as immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption, has also roles in detoxifying the body of heavy metals. Severe deficiency of vitamin C causes scurvy, whereas limited vitamin C intake causes symptoms, such as increased susceptibility to infections, loosening of teeth, dryness of the mouth and eyes, loss of hair, dry itchy skin, fatigue, and insomnia. In contrast, vitamin C can also act as a prooxidant, especially in the presence of transition metals, such as iron and copper, starting different hazardous radical reactions. Vitamin C can both act as a strong, efficient, and cheap antioxidant agent and, at the same time, behave as a radical promoter. Further investigations are needed to illuminate the dual roles of vitamin C",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Fadime Eryılmaz Pehlivan",authors:[{id:"200567",title:"Dr.",name:"Fadime",middleName:null,surname:"Eryılmaz Pehlivan",slug:"fadime-eryilmaz-pehlivan",fullName:"Fadime Eryılmaz Pehlivan"}]},{id:"69402",title:"Vitamin D Deficiency and Diabetes Mellitus",slug:"vitamin-d-deficiency-and-diabetes-mellitus",totalDownloads:1604,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Vitamin D (VD) is a molecule that can be synthesized directly in the humans’ body or enter the organism with food in the form of inactive precursors. To exert its biological action, VD undergoes two-stage hydroxylation (at the 25th and 1st position) catalyzed by cytochromes P450, the presence of which has already been shown in almost all tissues of the human body. The product of hydroxylation is hormone-active form of vitamin D–1,25(OH)2D. 1,25(OH)2D binds to specific vitamin D receptor (VDR) and regulates the expression of genes involved in bone remodeling (classical function) and genes that control immune response, hormone secretion, cell proliferation, and differentiation (nonclassical functions). VD deficiency is prevalent around the globe and may be one of the key factors for diabetes development. The direct association between vitamin D deficiency and type 1 (T1D) and type 2 (T2D) diabetes has been proven. Detection of VDR in pancreas and adipose tissue, skeletal muscles, and immune cells allowed implying the antidiabetic role of vitamin D by enhancing insulin synthesis and exocytosis, increasing the expression of the insulin receptor, and modulating immune cells’ functions. This chapter summarizes data about relationship between VD insufficiency/deficiency and development of T1D and T2D, and their complications.",book:{id:"7038",slug:"vitamin-d-deficiency",title:"Vitamin D Deficiency",fullTitle:"Vitamin D Deficiency"},signatures:"Ihor Shymanskyi, Olha Lisakovska, Anna Mazanova and Mykola Veliky",authors:null},{id:"76108",title:"Vitamin D Metabolism",slug:"vitamin-d-metabolism",totalDownloads:498,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Vitamin D plays an important role in bone metabolism. Vitamin D is a group of biologically inactive, fat-soluble prohormones that exist in two major forms: ergocalciferol (vitamin D2) produced by plants in response to ultraviolet irradiation and cholecalciferol (vitamin D3) derived from animal tissues or 7-dehydrocholesterol in human skin by the action of ultraviolet rays present in sunlight. Vitamin D, which is biologically inactive, needs two-step hydroxylation for activation. All of these steps are of crucial for Vitamin D to show its effect properly. In this section, we will present vitamin D synthesis and its action steps in detail.",book:{id:"10631",slug:"vitamin-d",title:"Vitamin D",fullTitle:"Vitamin D"},signatures:"Sezer Acar and Behzat Özkan",authors:[{id:"29878",title:"Dr.",name:"Behzat",middleName:null,surname:"Özkan",slug:"behzat-ozkan",fullName:"Behzat Özkan"},{id:"348287",title:"Dr.",name:"Sezer",middleName:null,surname:"Acar",slug:"sezer-acar",fullName:"Sezer Acar"}]},{id:"50754",title:"Medicinal Chemistry of Vitamin K Derivatives and Metabolites",slug:"medicinal-chemistry-of-vitamin-k-derivatives-and-metabolites",totalDownloads:1917,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Vitamin K acts as a cofactor for γ‐glutamyl carboxylase. Recently, various biological activities of vitamin K have been reported. Anti‐proliferative activities of vitamin K, especially in vitamin K3, are well known. In addition, various physiological and pharmacological functions of vitamin K2, such as transcription modulators as nuclear steroid and xenobiotic receptor (SXR) ligands and anti‐inflammatory effects, have been revealed in the past decade. Characterization of vitamin K metabolites is also important for clinical application of vitamin K and its derivatives. In this chapter, recent progress on the medicinal chemistry of vitamin K derivatives and metabolites is discussed.",book:{id:"5169",slug:"vitamin-k2-vital-for-health-and-wellbeing",title:"Vitamin K2",fullTitle:"Vitamin K2 - Vital for Health and Wellbeing"},signatures:"Shinya Fujii and Hiroyuki Kagechika",authors:[{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika"},{id:"180529",title:"Dr.",name:"Shinya",middleName:null,surname:"Fujii",slug:"shinya-fujii",fullName:"Shinya Fujii"}]}],onlineFirstChaptersFilter:{topicId:"42",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters: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:139,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:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,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:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. 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\r\n\tThis topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. Subjects will include an overview of oral diseases and infections, systemic diseases affecting the oral cavity, prevention, diagnosis, treatment, epidemiology, as well as current clinical recommendations for the management of oral, dental, and periodontal diseases.
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Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). Dr. Marinho's experience in Dentistry mainly covers the following subjects: oral diagnosis, oral radiology; oral medicine; lesions and oral infections; oral pathology, laser therapy and epidemiological studies.",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,series:{id:"3",title:"Dentistry",doi:"10.5772/intechopen.71199",issn:"2631-6218"},editorialBoard:[{id:"267724",title:"Prof.",name:"Febronia",middleName:null,surname:"Kahabuka",slug:"febronia-kahabuka",fullName:"Febronia Kahabuka",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZpJQAW/Profile_Picture_2022-06-27T12:00:42.JPG",institutionString:"Muhimbili University of Health and Allied Sciences, Tanzania",institution:{name:"Muhimbili University of Health and Allied Sciences",institutionURL:null,country:{name:"Tanzania"}}},{id:"70530",title:"Dr.",name:"Márcio",middleName:"Campos",surname:"Oliveira",slug:"marcio-oliveira",fullName:"Márcio Oliveira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRm0AQAS/Profile_Picture_2022-08-01T12:34:46.jpg",institutionString:null,institution:{name:"State University of Feira de Santana",institutionURL:null,country:{name:"Brazil"}}}]},onlineFirstChapters:{paginationCount:25,paginationItems:[{id:"82654",title:"Atraumatic Restorative Treatment: More than a Minimally Invasive Approach?",doi:"10.5772/intechopen.105623",signatures:"Manal A. 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