Goodness of fit (
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5532",leadTitle:null,fullTitle:"Immunotherapy - Myths, Reality, Ideas, Future",title:"Immunotherapy",subtitle:"Myths, Reality, Ideas, Future",reviewType:"peer-reviewed",abstract:"This is another attempt of InTechOpen to continue the dissemination of international knowledge and experience in the field of immunology. The present book includes a number of modern concepts of specialists and experts in the field of immunotherapy, covering the major topics and analyzing the history, current stage, and future ideas of application of modern immunomodulation. It is always a benefit, but also a compliment, to gather a team of internationally distinguished authors and to motivate them to reveal their expertise for the benefit of medical science and health practice. On behalf of all readers, immunologists, immunogeneticists, biologists, oncologists, microbiologists, virologists, hematologists, chemotherapists, health-care experts, as well as students and medical specialists, also on my personal behalf, I would like to extend my gratitude and highest appreciation to InTechOpen for giving me the unique chance to be the editor of this exclusive book.",isbn:"978-953-51-3106-9",printIsbn:"978-953-51-3105-2",pdfIsbn:"978-953-51-4864-7",doi:"10.5772/63291",price:139,priceEur:155,priceUsd:179,slug:"immunotherapy-myths-reality-ideas-future",numberOfPages:414,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"29b2bb4be497d30542f75271dfced920",bookSignature:"Krassimir Metodiev",publishedDate:"April 26th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5532.jpg",numberOfDownloads:29582,numberOfWosCitations:22,numberOfCrossrefCitations:19,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:32,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:73,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 18th 2016",dateEndSecondStepPublish:"June 8th 2016",dateEndThirdStepPublish:"September 12th 2016",dateEndFourthStepPublish:"December 11th 2016",dateEndFifthStepPublish:"January 10th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"173259",title:"Distinguished Prof.",name:"Krassimir",middleName:null,surname:"Metodiev",slug:"krassimir-metodiev",fullName:"Krassimir Metodiev",profilePictureURL:"https://mts.intechopen.com/storage/users/173259/images/5553_n.jpg",biography:"Professor Dr. Krassimir Metodiev, MD, PhD, DSc(Med), is head of the Department of Preclinical and Clinical Sciences, Medical University, Varna, Bulgaria; president, IMAB; vice president, FESCI; referent, UICC; and director, ARW Bioterrorism, Scientific Affairs’ Division, NATO. His specialties are immunology and clinical microbiology. \nHe has published over 250 papers, IF 175.00, 9 books on medicine, and 2 books on poetry. He is the editor in chief of the Journal of IMAB and editorial board member of IJIP, EJI, CEJM, JAA, and JISAO. He has edited Risk Infections and Possibilities for Biomedical Terrorism (IOS Press, NATO), Immunodeficiency (InTech Press), and Immunopathology and Immunomodulation (InTech Press). Prof. Dr. Metodiev was an invited speaker and a chairperson of congresses and symposiums, in over 60 countries worldwide. He is a holder of prestigious awards in Bulgaria, Israel, the UK, Germany, Italy, Greece, the USA, Japan, Canada, Australia, Brazil, Serbia, Turkey, Romania, and Slovenia. He is a board member of ISC, FESCI, EUCAST, ESC, ISAO/IFAO, EANO, ICHS, etc. Prof. Dr. Metodiev is also an honorary consul of Israel to Bulgaria.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Medical University of Varna",institutionURL:null,country:{name:"Bulgaria"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"899",title:"Cancer Immunology",slug:"pure-immunology-cancer-immunology"}],chapters:[{id:"54329",title:"Hematopoietic Cell Transplantation for Autoimmune Diseases: A Review of History, Current State, and Future Issues",doi:"10.5772/67604",slug:"hematopoietic-cell-transplantation-for-autoimmune-diseases-a-review-of-history-current-state-and-fut",totalDownloads:1322,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Autoimmune diseases are characterized by recurrent attacks and remissions, but as a rule they progress and eventually cause a severe disability and death. The present chapter contains general characteristics of autoimmune disease pathogenesis, ways to cause immune tolerance by hematopoietic cell transplantation (HCT), clinical aspects of the treatment for established autoimmune diseases with a special attention to multiple sclerosis (MS) and systemic sclerosis (SSc). A profound analysis of authors’ point of view and of the available literature has been performed. The promising results allows to consider HCT as a relevant treatment option for a certain autoimmune diseases.",signatures:"Igor B. Resnick, Krassimir Metodiev and Paula Lazarova",downloadPdfUrl:"/chapter/pdf-download/54329",previewPdfUrl:"/chapter/pdf-preview/54329",authors:[{id:"173259",title:"Distinguished Prof.",name:"Krassimir",surname:"Metodiev",slug:"krassimir-metodiev",fullName:"Krassimir Metodiev"},{id:"194796",title:"Dr.",name:"Igor",surname:"Resnick",slug:"igor-resnick",fullName:"Igor Resnick"}],corrections:null},{id:"54339",title:"Management and Supportive Care of Patients Undergoing Immunotherapy",doi:"10.5772/67372",slug:"management-and-supportive-care-of-patients-undergoing-immunotherapy",totalDownloads:1440,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In many tumor types, where the prognosis was shown to be extremely dismal before, immunotherapy is now a new beacon of hope to many patients. Immunotherapy has been approved for use in a many different cancers including metastatic melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, refractory Hodgkin’s lymphoma, metastatic bladder cancer advanced head and neck cancer, and the list keeps growing each day. It seems to be generally better tolerated in most patients and less toxic compared to what we have seen in different anticancer treatments from before. However, the toxicities here are termed immune-related adverse events. There is almost no prospective data on these toxicities, and guidelines or recommendations are mostly based on symptomatic management from the ongoing clinical trials. Treating oncologists need to be aware of the subtleties in presentation and the huge difference in the way we mange these side effects. Although most adverse events are low-grade and manageable, they have the potential to be life-threatening if not treated promptly. In this chapter, we address the different immune-related adverse events relating to the organ system they can involve, presentation and symptomatology, general recommendations of management, and individual toxicities. Keywords: immunotherapy, PD-1, CTLA-4.",signatures:"Bernardo L. Rapoport and Ronwyn van Eeden",downloadPdfUrl:"/chapter/pdf-download/54339",previewPdfUrl:"/chapter/pdf-preview/54339",authors:[{id:"174314",title:"Dr.",name:"Bernardo",surname:"Rapoport",slug:"bernardo-rapoport",fullName:"Bernardo Rapoport"},{id:"192707",title:"Dr.",name:"Ronwyn",surname:"Van Eeden",slug:"ronwyn-van-eeden",fullName:"Ronwyn Van Eeden"}],corrections:null},{id:"53284",title:"Immune Checkpoint Blockade and Adaptive Immune Resistance in Cancer",doi:"10.5772/66494",slug:"immune-checkpoint-blockade-and-adaptive-immune-resistance-in-cancer",totalDownloads:1684,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:1,abstract:"The clinical success of immune checkpoint blockers is a pivotal advancement for treating an increasing number of cancer types. However, immune checkpoint blockers still rarely induce complete remission and show little to no therapeutic efficacy in a significant percentage of cancer patients. Efforts are now underway to identify biomarkers that accurately predict which patients benefit from immune checkpoint blockers. Moreover, adaptive immune resistance can develop in tumors during treatment with immune checkpoint blockers. These adaptive resistance mechanisms in tumors might be disrupted by combining adjunctive immunotherapies, which could potentially improve the therapeutic efficacy of immune checkpoint blockers. This chapter discusses the mechanism of action of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint blockers and biomarkers that might predict clinical responses to these drugs. Lastly, ongoing research on mechanisms of tumor adaptive resistance could facilitate rationale design of adjunctive immunotherapies that can be synergistically combined with immune checkpoint blockers to more effectively treat cancer.",signatures:"Raymond M. Wong and Robert B. Cameron",downloadPdfUrl:"/chapter/pdf-download/53284",previewPdfUrl:"/chapter/pdf-preview/53284",authors:[{id:"192984",title:"Dr.",name:"Raymond",surname:"Wong",slug:"raymond-wong",fullName:"Raymond Wong"},{id:"195690",title:"Prof.",name:"Robert",surname:"Cameron",slug:"robert-cameron",fullName:"Robert Cameron"}],corrections:null},{id:"53068",title:"Present and Future of Subcutaneous Aero-Allergen Immunotherapy",doi:"10.5772/66286",slug:"present-and-future-of-subcutaneous-aero-allergen-immunotherapy",totalDownloads:1356,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The present review summarizes the literature-acquired knowledge as well as author’s own experience in conducting aero-allergen immunotherapy, particularly in subcutaneous route of administration (SCIT) of all modalities of respiratory allergy disease from allergic rhinosinusitis, bronchial asthma to united airway disease. Because of the better adherence resulting in appropriate efficacy in connection with satisfactory safety, the author favours conventional schedules of subcutaneous route of therapeutic intervention. Given the lack of specific biomarker in monitoring treatment course, the main control mechanism of efficacy is the evaluation of quality of life using simple evaluation scale as visual analogue scale or standardized respiratory allergy questionnaires. The future of allergen immunotherapy should be focused on new routes of allergen administration (e.g. oral, epicutaneous, intradermal, intralymphatic) and on the searching potential biomarkers which could be objectively measured and easily accessible from body fluids (blood, nasal secretion, sputum). The combination of estimated biomarkers obtained from biological samples in conjunction with evaluation of quality of life could lead to the generation of the overall satisfactory monitoring protocol.",signatures:"Norbert Lukan",downloadPdfUrl:"/chapter/pdf-download/53068",previewPdfUrl:"/chapter/pdf-preview/53068",authors:[{id:"43586",title:"Associate Prof.",name:"Norbert",surname:"Lukan",slug:"norbert-lukan",fullName:"Norbert Lukan"}],corrections:null},{id:"53117",title:"Vitamin B12: Could It Be a Promising Immunotherapy?",doi:"10.5772/65729",slug:"vitamin-b12-could-it-be-a-promising-immunotherapy-",totalDownloads:2247,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:1,abstract:"Vitamin B12 is a water-soluble vitamin and an important micronutrient with critical role in DNA, protein, and lipid synthesis. It is responsible for one-carbon metabolism and cell division of nervous and hematopoietic cells. Among its various functions, the role as immunomodulator in cellular immunity, especially in elevating the number of CD8+ cells and NK cells, attracts scientific interest. Many alternative anticancer and anti-inflammatory treatments involve the use of B12 together with other vitamins and nutrients, but still the scientific information is too obscure and insufficient. Controversial data link tumorigenesis with either increased or decreased B12 blood levels in different types of cancer. Dietary intake and additional supplement with the vitamin do not protect against cancer risk, but the dominant opinion is to integrate B12 as part of rational and healthy nutrition to ensure proper function of the immune system. This chapter will review in brief the most important facts for vitamin B12 functions and properties. We will try also to present in concise way the human immune system and the exact role of B12 in immune activity with emphasis on the questionable participation of vitamin B12 in the process of carcinogenesis and its significance as anticancer immunotherapy.",signatures:"Tatina T. Todorova, Neli Ermenlieva and Gabriela Tsankova",downloadPdfUrl:"/chapter/pdf-download/53117",previewPdfUrl:"/chapter/pdf-preview/53117",authors:[{id:"175504",title:"Dr.",name:"Tatina",surname:"Todorova",slug:"tatina-todorova",fullName:"Tatina Todorova"},{id:"176473",title:"Dr.",name:"Gabriela",surname:"Tsankova",slug:"gabriela-tsankova",fullName:"Gabriela Tsankova"},{id:"176474",title:"Dr.",name:"Neli",surname:"Ermenlieva",slug:"neli-ermenlieva",fullName:"Neli Ermenlieva"}],corrections:null},{id:"54307",title:"Immunotherapy in Gynecologic Cancers",doi:"10.5772/67605",slug:"immunotherapy-in-gynecologic-cancers",totalDownloads:1590,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"During the last years, significant progress in the understanding of signaling pathways of immune cells has revive the field of immune therapy for cancer. In this chapter, we explain the recent immunotherapy-based strategies for the treatment of gynecological cancers including cervical cancer, endometrial cancer, ovarian cancer, and vulvar cancer. This work will mainly focus on emerging clinical data on immune checkpoint inhibitors. But also data on adoptive T cell therapies and vaccines will be presented. It is anticipated that in future biomarker-guided randomized trials will provide better approaches in terms of response and resistance to immune therapy. The use of combination therapy for gynecological cancer might be one possible approach to overcome resistance.",signatures:"Marcus Vetter and Viola Heinzelmann-Schwarz",downloadPdfUrl:"/chapter/pdf-download/54307",previewPdfUrl:"/chapter/pdf-preview/54307",authors:[{id:"182412",title:"Prof.",name:"Viola",surname:"Heinzelmann",slug:"viola-heinzelmann",fullName:"Viola Heinzelmann"},{id:"192628",title:"Dr.",name:"Marcus",surname:"Vetter",slug:"marcus-vetter",fullName:"Marcus Vetter"}],corrections:null},{id:"53551",title:"Aptamers as a Promising Therapeutic Tool for Cancer Immunotherapy",doi:"10.5772/66964",slug:"aptamers-as-a-promising-therapeutic-tool-for-cancer-immunotherapy",totalDownloads:1807,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Aptamers are single-chained RNA or DNA oligonucleotides (ODNs) with a three-dimensional conformation that provides the ability to fit their targets with high affinity and specificity obtained by a method called SELEX. Cancer immunotherapy has nowadays come back to prominence due to its encouraging results in the clinic with monoclonal antibodies. Aptamers display some important advantages over antibodies at the time of translation into the clinic. They are very suitable for targeting and delivery, reducing off-target side effects, and increasing the therapeutic index of a given strategy. Hundreds of aptamers have been described for very different purposes within biomedical research. Some of the aptamers described recently have been isolated with immunotherapeutic applications to overcome current challenges in cancer immunotherapy. To elicit a specific antitumor immune response, some of these aptamers are engineered to activate co-stimulatory receptors or blocking immunosuppressive signals. Aptamers would hopefully gain an important niche in cancer immunotherapy due to their specific properties.",signatures:"Mario Martínez Soldevilla, Helena Villanueva and Fernando Pastor",downloadPdfUrl:"/chapter/pdf-download/53551",previewPdfUrl:"/chapter/pdf-preview/53551",authors:[{id:"193041",title:"Dr.",name:"Mario",surname:"M. Soldevilla",slug:"mario-m.-soldevilla",fullName:"Mario M. Soldevilla"},{id:"195162",title:"Dr.",name:"Helena",surname:"Villanueva",slug:"helena-villanueva",fullName:"Helena Villanueva"},{id:"195163",title:"Dr.",name:"Fernando",surname:"Pastor",slug:"fernando-pastor",fullName:"Fernando Pastor"}],corrections:null},{id:"53372",title:"Antigen-Presenting Cell/Tumour Cell Hybrid Vaccines in Cancer Immunotherapy",doi:"10.5772/66557",slug:"antigen-presenting-cell-tumour-cell-hybrid-vaccines-in-cancer-immunotherapy",totalDownloads:1163,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In recent years, there has been a considerable interest in the development of immunotherapeutic approaches for treating cancers, including strategies for inducing antigen-specific cytotoxic T cells (CTLs) capable of killing tumour cells in situ. These approaches include both the active induction of CTLs by vaccination of tumour bearing patients, and the ex vivo expansion of tumour-specific CTLs for adoptive cellular transfer. One promising approach has been through the generation of hybrid cells, formed by fusion of professional antigen presenting cells (pAPCs) with tumour cells expressing relevant tumour associated antigens. Dendritic cells (DCs) represent the most potent form of pAPCs, and have been widely used in the generation of APC/tumour cell hybrid vaccines, in the context of a range of tumour types. Studies of fusion cell vaccines in animals have demonstrated not only the induction of tumour-specific CTLs, but also protection against subsequent tumour challenge and regression of established tumours. Results of clinical trials in patients have been less dramatic, but have shown the ability of hybrid vaccines to induce tumour-specific T cell responses, in some instances associated with disease stabilization or tumour regression. In addition to dendritic cell fusion vaccines, a number of non-DC fusion vaccines have been described.",signatures:"Yehia S. Mohamed, Wafaa S. Khalaf and Michael J. Browning",downloadPdfUrl:"/chapter/pdf-download/53372",previewPdfUrl:"/chapter/pdf-preview/53372",authors:[{id:"192648",title:"Dr.",name:"Michael",surname:"Browning",slug:"michael-browning",fullName:"Michael Browning"},{id:"192651",title:"Dr.",name:"Yehia",surname:"Mohamed",slug:"yehia-mohamed",fullName:"Yehia Mohamed"}],corrections:null},{id:"53256",title:"CARs on the Highway: Chimeric Antigen Receptor Modified T Cells for the Adoptive Cell Therapy of Malignant Diseases",doi:"10.5772/66496",slug:"cars-on-the-highway-chimeric-antigen-receptor-modified-t-cells-for-the-adoptive-cell-therapy-of-mali",totalDownloads:2295,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Adoptive therapy of malignant diseases by chimeric antigen receptor (CAR) redirected T cells takes advantage of the patient’s own immune system to recognize and destroy cancer cells. This is impressively demonstrated by the induction of complete and lasting remissions of leukemia with CAR-engineered T cells in early phase trials. Recent developments in optimizing the CAR design, in the recognition of target cells and the production of modified cells for clinical use, have paved the path for a broader application than currently explored. The chapter reviews the differences in CAR design, the success in the treatment of hematologic malignancies, the challenges in treating solid cancer, the treatment-related toxicities, and strategies to improve safety of CAR T cell therapy. Challenges for future applications are discussed.",signatures:"Astrid Holzinger and Hinrich Abken",downloadPdfUrl:"/chapter/pdf-download/53256",previewPdfUrl:"/chapter/pdf-preview/53256",authors:[{id:"39699",title:"Prof.",name:"Hinrich",surname:"Abken",slug:"hinrich-abken",fullName:"Hinrich Abken"},{id:"196419",title:"Dr.",name:"Astrid",surname:"Holzinger",slug:"astrid-holzinger",fullName:"Astrid Holzinger"}],corrections:null},{id:"53413",title:"The Memory Activation of NK Cells: New Methods in Cancer Immunotherapy",doi:"10.5772/66555",slug:"the-memory-activation-of-nk-cells-new-methods-in-cancer-immunotherapy",totalDownloads:1559,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Cancer remains a main cause of mortality, despite the research efforts to unravel molecular mechanisms and for developing personalized targeted therapies with acceptable side effects. In cancer, both players, the aggressor (tumor cells) and the endogenous defenders (immune cells), are key therapeutic targets. Immunotherapy is nowadays considered the fourth therapeutical approach in cancer, complementing and sometimes replacing surgery and chemo‐ and radiotherapy. Natural killer (NK) cells, generally considered part of the innate immune system, play a critical role in defense against pathogens and tumors. Immunological memory is a hallmark of the adaptive immune system. However, NK cells have been shown to mediate Ag‐specific recall responses and acquire immunological memory in a manner similar to that of T and B cells. This chapter summarizes evidence for NK cell immunotherapy, evidence and characteristics of NK cell memory and mechanisms involved in the generation and survival of these cells. There is no doubt that NK cells have major role in cancer treatments and viral infections, and in the future, NK cell immunotherapy from “a new hope” may become “a reality” for malignant diseases.",signatures:"Gheorghita Isvoranu",downloadPdfUrl:"/chapter/pdf-download/53413",previewPdfUrl:"/chapter/pdf-preview/53413",authors:[{id:"193129",title:"Ph.D.",name:"Gheorghita",surname:"Isvoranu",slug:"gheorghita-isvoranu",fullName:"Gheorghita Isvoranu"}],corrections:null},{id:"54286",title:"Therapeutic Antibody‐Based Drugs in the Treatment of Human Inflammatory Disorders",doi:"10.5772/67478",slug:"therapeutic-antibody-based-drugs-in-the-treatment-of-human-inflammatory-disorders",totalDownloads:2494,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Inflammation causes debilitating human conditions and older treatments rely on global immunosuppression that non‐specifically alleviates symptoms. Currently, several monoclonal antibodies (mAbs) are available that specifically block pro‐inflammatory cytokines. These include mAbs specific to tumour necrosis factor (TNF), interleukin (IL)‐1β, IL‐6, IL‐17 and IL‐12/IL‐23. The chapter summarises the key elements in human inflammatory disease conditions, including various forms of arthritis, psoriasis, Crohn's disease and ulcerative colitis, plus pyrin‐associated inflammatory syndromes and periodic fevers, to explain the benefit of cytokine neutralisation through mAb‐type reagents. The chapter reviews the efficacy and safety of the current repertoire of anti‐cytokine/cytokine receptor mAbs. It also discusses the known side effects and adverse events that are sometimes associated with systemic blockade of cytokines in vivo, and concludes that the accumulating knowledge of treatment failures can reveal unappreciated aspects of cytokine biology and even new treatment opportunities. The chapter includes mention of the rapidly expanding cohort of biosimilar mAbs and the mAbs to IL‐4, IL‐5 and IL‐13 that are now emerging, in addition to the need for treatments for disorders that remain refractory to the current repertoire of anti‐cytokine mAbs and conventional treatments. Thus, here we summarise the current status of anti‐cytokine mAbs for human inflammatory diseases.",signatures:"Lisa M. Sedger, Charani Ranasinghe, Michael F. McDermott and\nParisa Asvadi",downloadPdfUrl:"/chapter/pdf-download/54286",previewPdfUrl:"/chapter/pdf-preview/54286",authors:[{id:"194737",title:"Dr.",name:"Lisa",surname:"Sedger",slug:"lisa-sedger",fullName:"Lisa Sedger"}],corrections:null},{id:"53198",title:"Immunotherapeutic Biologic Agents to Treat Autoinflammatory Diseases",doi:"10.5772/66547",slug:"immunotherapeutic-biologic-agents-to-treat-autoinflammatory-diseases",totalDownloads:1600,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In recent years, innovative treatment for patients with autoimmune and autoinflammatory diseases has advanced in concert with our increased understanding of molecular and clinical immunology. Deeper understanding of autoimmunity has allowed for the development of cutting-edge biologic drugs for patients with relatively common autoimmune diseases. During this same period, knowledge regarding the molecular bases of autoinflammatory genetic diseases has also greatly expanded. Biologic immunotherapeutic agents developed for autoimmune diseases that primarily target cytokines that are also dysregulated in the uncommon autoinflammatory diseases are the focus of this article. In the following pages, selected genetic autoinflammatory diseases and key immunotherapeutic treatment approaches are addressed. The current understanding of these diseases and mechanisms by which therapeutic agents may benefit patients are reviewed. Indications, risks, and additional considerations for the use of these agents in treatment of autoinflammatory disorders are addressed as well.",signatures:"Barbara E. Ostrov",downloadPdfUrl:"/chapter/pdf-download/53198",previewPdfUrl:"/chapter/pdf-preview/53198",authors:[{id:"192933",title:"Dr.",name:"Barbara",surname:"Ostrov",slug:"barbara-ostrov",fullName:"Barbara Ostrov"}],corrections:null},{id:"53471",title:"Immunotherapy for Fungal Infections",doi:"10.5772/66164",slug:"immunotherapy-for-fungal-infections",totalDownloads:1644,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Opportunistic fungal infections are a major health problem being appointed by some studies as the fourth main cause of hospital-acquired infection in susceptible populations. The constantly growing incidences of these diseases are associated with the growing number of susceptible individuals, such as immunocompromised individuals (leukemia, AIDS, etc) and treatment-induced immunodeficiency (hematopoietic stem cell, solid organ transplant, anticancer therapy). Furthermore, other advances in medical care, patient’s long-term hospitalization and antimicrobial therapies have created several vulnerable populations to fungal infections. Currently, antifungal drug therapies are several times inefficient, and the poor outcomes are linked to difficulties in the early diagnosis of fungal infections and drug resistance among fungal pathogens. In this context, novel therapeutic approaches are welcome to stimulate efficiently the host immune response to eliminate the fungal pathogen. This chapter is intended to review advances in immunotherapy strategies for fungal infections.",signatures:"Érico S. Loreto, Juliana S. M. Tondolo, Sydney H. Alves and Janio M.\nSanturio",downloadPdfUrl:"/chapter/pdf-download/53471",previewPdfUrl:"/chapter/pdf-preview/53471",authors:[{id:"192918",title:"Prof.",name:"Janio",surname:"Santurio",slug:"janio-santurio",fullName:"Janio Santurio"}],corrections:null},{id:"53428",title:"Immunotherapy with Dialyzable Leukocyte Extracts Containing Transfer Factor",doi:"10.5772/66524",slug:"immunotherapy-with-dialyzable-leukocyte-extracts-containing-transfer-factor",totalDownloads:2038,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Dialyzable leukocyte extracts (DLE) are complexes consisting of a large number of low molecular weight substances. These extracts possess immunomodulatory properties, which are mainly attributed to small peptides with molecular weight of 3.5–6.0 kDa called “transfer factor.” This chapter reviews the nature and immunological characteristics of DLE containing transfer factor (TF), their mechanism of action and the possible uses as immunomodulators in human and veterinary medicine. A main advantage of TF-preparations as immunotherapeutic agents is that they induce a rapid immune response against the pathogen (within 24 h) and thereby reduce the time for the patient immune response by 9–13 days. The low level of difficulty of the process of obtaining protocols determines their relatively low cost and the possibility to combine them with other therapeutic agents during treatment makes them subject to medical applications in the future, including against some new diseases.",signatures:"Atanas Arnaudov",downloadPdfUrl:"/chapter/pdf-download/53428",previewPdfUrl:"/chapter/pdf-preview/53428",authors:[{id:"192002",title:"Associate Prof.",name:"Atanas",surname:"Arnaudov",slug:"atanas-arnaudov",fullName:"Atanas Arnaudov"}],corrections:null},{id:"53556",title:"Exopolysaccharides from Bacteria with Novel Application",doi:"10.5772/66535",slug:"exopolysaccharides-from-bacteria-with-novel-application",totalDownloads:1690,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The physiological role of EPS depends on the ecological niches and the natural environment in which microorganisms have been isolated. In this chapter, data on EPS production and the effect of EPS on corrosion of steel produced by Lactobacillus sp. are presented and discussed. Lactobacillus plantarum Ts was obtained from the Collection of Department of Biology, Shumen University. It was tested for its ability to produce exopolysaccharides when cultivated in a medium containing 10% sucrose. It could be underlined that 10% sucrose in the medium stimulated the process of protection of corrosion. Also, the biofilm in vitro in the combined cultivation of Staphylococcus aureus and the Lactobacillus plantarum Ts probiotic bacterium on the surface of different metal materials for fixed dental prostheses was investigated [unpublished results]. The structure of layer over steel plates was analyzed by scanning electron microscopy (SEM) JSM 5510. In our opinion, more detailed research is needed to be done in the future, and the possibilities should be analyzed for the creation of a thin biofilm from a probiotic bacterium or an exopolysaccharide this bacterium has produced, which would protect the implants against the growth of a pathogenic biofilm.",signatures:"Tsveteslava Ignatova-Ivanova",downloadPdfUrl:"/chapter/pdf-download/53556",previewPdfUrl:"/chapter/pdf-preview/53556",authors:[{id:"194770",title:"Prof.",name:"Tsveteslava Veselinova",surname:"Ignatova-Ivanova",slug:"tsveteslava-veselinova-ignatova-ivanova",fullName:"Tsveteslava Veselinova Ignatova-Ivanova"}],corrections:null},{id:"54060",title:"Unmet Needs in Understanding Sublingual Immunotherapy to Grass Pollen",doi:"10.5772/67212",slug:"unmet-needs-in-understanding-sublingual-immunotherapy-to-grass-pollen",totalDownloads:1632,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The lack of medication for allergy symptoms at the end of the last millennium has been the promoter of the idea of treating allergies as if you were treating an infectious disease, by vaccination prophylaxis. Two forms of AIT 1) subcutaneous immunotherapy (SCIT) and 2) sublingual immunotherapy (SLIT) are used in the world. Considerable interest has emerged in SLIT both scientifically and especially financially. SLIT is not a new treatment modality. First description dates back to 1900 when H. Curtis. It was relatively widely used until the late 1970’s mainly in US by homeopathic therapists.",signatures:"Gabriele Di Lorenzo, Maria Stefania Leto-Barone, Simona La Piana\nand Danilo Di Bona",downloadPdfUrl:"/chapter/pdf-download/54060",previewPdfUrl:"/chapter/pdf-preview/54060",authors:[{id:"73451",title:"Prof.",name:"Gabriele",surname:"Di Lorenzo",slug:"gabriele-di-lorenzo",fullName:"Gabriele Di Lorenzo"},{id:"192627",title:"Dr.",name:"Danilo",surname:"Di Bona",slug:"danilo-di-bona",fullName:"Danilo Di Bona"},{id:"192742",title:"Dr.",name:"Maria",surname:"Stefania Leto-Barone",slug:"maria-stefania-leto-barone",fullName:"Maria Stefania Leto-Barone"},{id:"192743",title:"Dr.",name:"Simona",surname:"La Piana",slug:"simona-la-piana",fullName:"Simona La Piana"}],corrections:null},{id:"53596",title:"Allergen-Specific Immunotherapy Follow-Up by Measuring Allergen-Specific IgG as an Objective Parameter",doi:"10.5772/66711",slug:"allergen-specific-immunotherapy-follow-up-by-measuring-allergen-specific-igg-as-an-objective-paramet",totalDownloads:2023,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:1,abstract:"The clinical efficacy of the allergen‐specific immunotherapy (AIT) has been well‐documented using inhalant or hymenoptera‐derived allergens in atopic patients with corresponding specific IgE antibodies. AIT is considered as the unique treatment that is capable of modifying the natural course of the allergic disease because it induces a variety of immunological mechanisms, with emphasis in the production of blocking IgG antibodies by IL‐10‐stimulated B cells due to the generation of Treg, Breg, or even Th2 cells. Thus, the measurement of specific IgG subclasses, particularly IgG4, to the crude extract or more importantly to allergen components, might be a useful and potential tool to follow‐up objectively the patients undergoing AIT in addition to clinical parameters. In this chapter, the authors have emphasized a very sensitive and highly specific reverse ELISA, developed by them, to measure IgG subclasses directed to clinically relevant natural allergens that are undoubtedly better when compared to those obtained with recombinant counterparts. Such a technique may produce more authentic results taking into account the IgG subclass binding capacity to a particular allergen and might be a valuable and alternative method for monitoring activation of tolerance‐inducing mechanisms in patients under AIT.",signatures:"Ernesto Akio Taketomi, Juliana Silva Miranda, Jair Pereira da Cunha-\nJúnior and Deise Aparecida de Oliveira Silva",downloadPdfUrl:"/chapter/pdf-download/53596",previewPdfUrl:"/chapter/pdf-preview/53596",authors:[{id:"193302",title:"M.D.",name:"Ernesto",surname:"Taketomi",slug:"ernesto-taketomi",fullName:"Ernesto Taketomi"},{id:"193303",title:"Dr.",name:"Juliana",surname:"Miranda",slug:"juliana-miranda",fullName:"Juliana Miranda"},{id:"193304",title:"Dr.",name:"Jair",surname:"Cunha Junior",slug:"jair-cunha-junior",fullName:"Jair Cunha Junior"},{id:"193305",title:"Dr.",name:"Deise",surname:"Silva",slug:"deise-silva",fullName:"Deise Silva"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5484",title:"Biology of Myelomonocytic Cells",subtitle:null,isOpenForSubmission:!1,hash:"861561e42fe02bd42af3082330cecf99",slug:"biology-of-myelomonocytic-cells",bookSignature:"Anirban Ghosh",coverURL:"https://cdn.intechopen.com/books/images_new/5484.jpg",editedByType:"Edited by",editors:[{id:"46516",title:"Dr.",name:"Anirban",surname:"Ghosh",slug:"anirban-ghosh",fullName:"Anirban Ghosh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5991",title:"Natural Killer Cells",subtitle:null,isOpenForSubmission:!1,hash:"ea5a1d2f5030a6af3f29cc75fdb9f559",slug:"natural-killer-cells",bookSignature:"Mourad Aribi",coverURL:"https://cdn.intechopen.com/books/images_new/5991.jpg",editedByType:"Edited by",editors:[{id:"40046",title:"Prof.",name:"Mourad",surname:"Aribi",slug:"mourad-aribi",fullName:"Mourad Aribi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6004",title:"Lymphocyte Updates",subtitle:"Cancer, Autoimmunity and Infection",isOpenForSubmission:!1,hash:"2a9634b93e9b1d409b3b47d472960c55",slug:"lymphocyte-updates-cancer-autoimmunity-and-infection",bookSignature:"Gheorghita Isvoranu",coverURL:"https://cdn.intechopen.com/books/images_new/6004.jpg",editedByType:"Edited by",editors:[{id:"193129",title:"Ph.D.",name:"Gheorghita",surname:"Isvoranu",slug:"gheorghita-isvoranu",fullName:"Gheorghita Isvoranu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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. 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What Has Changed in Diagnosis and Treatment",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tKeratoconus is a corneal ectatic disorder that is very far to be completely understood and successfully managed. Thanks to great innovations in different technology fields, physicians now have more options in order to obtain a more precise and earlier diagnosis, such as Scheimpflug camera based device, or corneal biomechanical properties analysis. Some years ago, patients with progressive keratoconus were intended to undergo corneal transplant, and now corneal crosslinking procedure has changed this course, and it is possible to stabilize progression of this disease. Being a fairly new procedure, corneal crosslinking has already changed since its introduction, and it is reasonable to expect further news about it. Even if new devices and procedures are always purposed, it is important to verify them because “new” is not always “better”. Because of that, latest methods need to be methodologically verified.
\r\n\r\n\tThis book will provide general ophthalmologists, corneal specialists, optometrists and physicians interested in this disease, a complete vision of the latest news regarding the diagnosis and the management of keratoconus.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"fbb96c980c0a79b398c2f56a2888e6c9",bookSignature:"Prof. Michele Lanza",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9503.jpg",keywords:"Corneal Topography, Corneal Tomography, Placido Disc, Scheimpflug Camera, Corneal Aberrations, Corneal Degenerations, Early Diagnosis, Corneal Ectasia, Tear Film Alterations, Systemic Association, Corneal Biomechanical Properties, Corneal Deformation",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 1st 2020",dateEndSecondStepPublish:"July 22nd 2020",dateEndThirdStepPublish:"September 20th 2020",dateEndFourthStepPublish:"December 9th 2020",dateEndFifthStepPublish:"February 7th 2021",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Michele Lanza, after graduating in Medicine and Surgery at Medical School of Seconda Università di Napoli, he started the residency program in Ophthalmology (2001). Today he is an Associate Professor in Ophthalmology at Università della Campania, Luigi Vanvitelli. His field of interest are anterior segment disease, keratoconus, glaucoma, corneal distrophies, and cataract.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"240088",title:"Prof.",name:"Michele",middleName:null,surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza",profilePictureURL:"https://mts.intechopen.com/storage/users/240088/images/system/240088.png",biography:"Michele Lanza is Associate Professor of Ophthalmology at Università della Campania, Luigi Vanvitelli, Napoli, Italy. His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"7218",title:"OCT",subtitle:"Applications in Ophthalmology",isOpenForSubmission:!1,hash:"e3a3430cdfd6999caccac933e4613885",slug:"oct-applications-in-ophthalmology",bookSignature:"Michele Lanza",coverURL:"https://cdn.intechopen.com/books/images_new/7218.jpg",editedByType:"Edited by",editors:[{id:"240088",title:"Prof.",name:"Michele",surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7858",title:"A Practical Guide to Clinical Application of OCT in Ophthalmology",subtitle:null,isOpenForSubmission:!1,hash:"8e2d479cc9258dee430f8ba4c353c468",slug:"a-practical-guide-to-clinical-application-of-oct-in-ophthalmology",bookSignature:"Michele Lanza",coverURL:"https://cdn.intechopen.com/books/images_new/7858.jpg",editedByType:"Edited by",editors:[{id:"240088",title:"Prof.",name:"Michele",surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10343",title:"Ocular Hypertension",subtitle:"The Knowns and Unknowns",isOpenForSubmission:!1,hash:"0ff71cc7e0d9f394f41162c0c825588a",slug:"ocular-hypertension-the-knowns-and-unknowns",bookSignature:"Michele Lanza",coverURL:"https://cdn.intechopen.com/books/images_new/10343.jpg",editedByType:"Edited by",editors:[{id:"240088",title:"Prof.",name:"Michele",surname:"Lanza",slug:"michele-lanza",fullName:"Michele Lanza"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"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"}}]},chapter:{item:{type:"chapter",id:"49615",title:"Processing of Multichannel Remote-Sensing Images with Prediction of Performance Parameters",doi:"10.5772/61853",slug:"processing-of-multichannel-remote-sensing-images-with-prediction-of-performance-parameters",body:'Remote-sensing (RS) data are widely used for numerous applications [1], [2]. Primary RS images acquired onboard of airborne or spaceborne carriers and intended for Earth surface monitoring are usually not ready for direct use and, thus, are subject to a certain preprocessing. This preprocessing can be carried out in several stages and includes the following operations: geo-referencing and calibration, blind estimation of noise/distortion characteristics, pre-filtering, lossless or lossy compression, [1], [2], etc. These operations can be distributed between onboard and on-land computer means (processors) in different ways depending upon many factors [3-5].
Regardless of the distribution of functions, the operations onboard are usually performed in a fully automatic manner (although there can be some changes in algorithm parameters by command passed from Earth). In turn, the operations carried out on land can be, in general, performed in an interactive manner and labor of highly qualified experts is exploited for this purpose. However, a certain degree of automation of on-land data processing is required as well. The need in processing automation is especially high if one deals with multichannel (e.g., hyperspectral) RS data [6], where the number of channels (components, sub-bands) can reach hundreds. Such RS images have become popular and widespread (available) currently due to their (potential) ability to provide rich information for various applications [6], [7].
Meanwhile, the multichannel nature of RS data results in new problems in their processing [3], [8]. The main problems and actual questions are the following:
How to manage large volumes of acquired data with maximal or appropriate efficiency (here, different criteria of efficiency can be used)?
Is it possible to skip some operations of data processing if their efficiency is not high and, consequently, if it is not worth performing them?
The latter question can be mainly addressed as mentioned below. It is strictly connected with other questions as follows:
Is it possible to predict the performance of some standard operations of RS data (image) processing?
What is the accuracy of such a prediction and is this accuracy high enough to undertake a decision to skip carrying out an operation or to set a certain value of some parameter used in the image-processing chain [9]?
This chapter will focus on two typical operations of multichannel RS data processing, namely, filtering and lossy compression. While considering them, the fact that the acquired images are noisy is taken into account. One can argue that noise is not seen in many RS images (or components of these images). This is true, and noise cannot be observed in approximately 80% of the visualized sub-band images of hyperspectral data. This is explained by the peculiarities of human vision, which does not see noise if peak signal-to-noise ratio (PSNR) in a given single-channel (component) image exceeds 32–38 dB. However, recent studies [7], [10-12] have demonstrated that noise is present in all sub-band images and this is due to the principle of operation of hyperspectral imagers.
Moreover, it has been shown in [10], [11] that noise is (can be) of quite a complex nature and the noise acquired in multichannel RS images has specific properties. First, it is signal-dependent [10], [11], [13]. Second, it is of essentially a different intensity (see Abramov et al., 2015 in [14]). More precisely, the wide variation of dynamic range and noise intensity in sub-band images jointly leads to wide limits of signal-to-noise ratio (SNR) in components of multichannel images. This has led to the use of the term “junk bands” [15] and different strategies of coping with noisy channels in multichannel data. Some researchers prefer to use these sub-bands in further processing while others propose to remove them; it is also discussed whether they can be filtered or not [15]. It has been shown that if filtering of these junk bands is efficient, this can improve the classification of hyperspectral data [16]. However, the aforementioned questions concern the efficiency of image preprocessing and its prediction.
The questions raised can be partly answered with the results obtained in recent research. The objective is to show that important performance parameters of image denoising and/or lossy compression can be quickly and quite accurately predicted using simple input parameter(s) and dependences obtained in advance. The obtained results are divided into two parts. The first part deals with the prediction of filtering efficiency. This research has started in 2013 [17] and has its history in a study conducted in [18]. The second part relates to the compression of noisy images [19], [20]. In fact, the results obtained for predicting the parameters of lossy compression can be treated as based on the same principle as that for image filtering and for further research.
Before taking the image performance criteria and preprocessing techniques into consideration, it is important to note the following: first, there are two hypotheses. It is supposed that noise type is known or determined in advance. It is also assumed that its parameters are either known or accurately pre-estimated. It is to be noted that, currently, there are quite a few efficient methods for estimating the parameters of pure additive noise [8], [21-25], speckle noise [26], and different types of signal-dependent noise [10-12], [27], [28]. The noise parameters are taken into account by the most modern filtering techniques that belong to the families of orthogonal-transform-based filters [29-33] and nonlocal filters, for example, block-matching and three-dimensional filtering (BM3D) [34]. The same relates to modern methods of lossy compression of noisy images [19], [35].
Second, we restrict ourselves to consider the image- filtering and compression techniques based on discrete cosine transform (DCT). This is explained using several reasons. DCT is a powerful orthogonal transform widely exploited in image processing. Filters and compression techniques based on DCT are currently among the best [34]. They can be quite easily adapted to the signal-dependent noise directly [32], [36] or equipped with proper variance-stabilizing transformations (VST) [19], [32], [37]. This restriction does not mean that the approach to prediction cannot be applied to other filtering and lossy compression techniques. This approach should be applicable (with certain modifications) but is yet to be thoroughly checked.
Third, in the analysis of the prediction approach, traditional quality metrics are employed such as mean square error (MSE) and peak signal-to-noise ratio (PSNR), as well as some visual quality metrics such as PSNR human visual system masking metric (PSNR-HVS-M) [38]. Behavior and properties of traditional metrics are understood well by those dealing with image processing. Although PSNR-HVS-M is less popular, this is one of the best metrics that takes into account the peculiarities of human visual system (HVS) and that can be calculated for either one component of a multichannel image or a group of components of a multichannel image. It is expressed in dB, and it is usually either slightly smaller than PSNR (for annoying types of distortions like spatially correlated noise) or larger than PSNR (if distortions are masked by texture). This is important since we assume that the processing of multichannel images is carried out either component-wise or in groups of channel images, where a group includes the entire image in marginal case.
Fourth, other criteria of image-processing efficiency, such as classification accuracy, object detectability, etc., are important for the preprocessed RS data. We are unable to predict them, but recent research shows [39] that these criteria are connected with the traditional criteria of image processing. Thus, it is expected that if good values of conventional and HVS metrics are provided due to preprocessing, appropriate classification accuracy and other criteria will be attained.
This chapter considers the following model of an observed multichannel image:
where
and input PSNR
The same assumptions are valid for input
After applying a considered filter, one obtains a filtered image
Output
Then, one has to characterize the efficiency of filtering. One way to do this is to use
Small values of the ratio in expression (6) and large values of expressions (7) and (8), both expressed in dB, are evidence in favor of efficient filtering.
Similarly, after lossy compression, one obtains
occurs to be less than
on QS for the lossy DCT-based coder AGU [42] for two known gray-scale test images Airfield (Fig. 1(b)) and Frisco (Fig. 1(c)) corrupted by additive white Gaussian noise (AWGN) with variance
Dependences
The lossy compression in the neighborhood of OOP has obvious advantages. Compressed images have high quality, and, at the same time, they have CR considerably larger than for lossless compression [9], [44]. Because of these benefits, the lossy compression of noisy images in the OOP neighborhood is considered. If OOP does not exist, nevertheless, the recommended setting
where
Certainly, there are also other valuable performance criteria. For image pre-filtering, it is important to know the computational efficiency of the denoising method and how easily it can be implemented, especially onboard. For image lossy compression, it is important to know CR provided and how easily it can be attained. To partly address these issues, the filtering and compression techniques are briefly described.
DCT-based filtering [18], [30] is performed in a block-wise manner, where 8 × 8 pixels are a typically set block size. Filtering can be performed with nonoverlapping, partly overlapping, and fully overlapping blocks. In the latter case, filtering efficiency (expressed in improvement of PSNR (
There are three main steps in processing: direct 2D DCT in each block; thresholding of DCT coefficients; inverse DCT applied to thresholded DCT coefficients; then, the filtered data from overlapping blocks are aggregated. Within this structure, different variants of thresholding are possible but employing hard thresholding is preferred, where DCT coefficient values remain unchanged if their amplitudes exceed a threshold or are assigned zero values otherwise. If one deals with AWGN, the threshold is set fixed as
For spatially uncorrelated signal-dependent noise with
Finally, for spatially correlated and signal-dependent noise with
In expressions (14–16),
Conventional BM3D [34] is a more sophisticated denoising method. It presumes search for similar patches (blocks), with their joint processing in a 3D manner using DCT and Haar transform, and post-processing stage. This filtering principle, originally designed to cope with AWGN in gray-scale images, has been later adapted to the cases of signal-dependent noise after a proper VST [37], spatially correlated noise [45] and color (three-channel) images corrupted by AWGN [46]. The BM3D and its modifications provide a slightly better performance than the corresponding modifications of the conventional DCT-based denoising by the expense of considerably more extensive computations.
The lossy compression technique called AGU [42] is based on DCT in 32 × 32 pixel blocks, a more efficient (compared to JPEG) coding of quantized DCT coefficients and post-processing to remove the blocking artifacts after decompression. This coder is quite simple but slightly more efficient than JPEG 2000) or set partitioning in hierarchical trees (SPIHT) in rate/distortion sense. This coder has 3D version [19] and CR for both 2D and 3D versions is controlled (changed) by QS.
The main idea of filtering efficiency prediction is the following [17]. Suppose there is some input parameter(s) able to jointly characterize image complexity and noise intensity and also there is some output parameter(s) capable of adequately describing the image denoising efficiency. Assume that there is a rather strict connection between these input and output parameters that allows predicting output value(s) having input value(s).
An additional assumption (and requirement to prediction) is that input parameter(s) have to be calculated easily and quickly enough, faster than denoising itself (otherwise, the prediction becomes useless). If all these assumptions are valid, it becomes possible to determine a predicted output value before starting image filtering and to decide whether it is worth filtering a given image (component) or not. Another decision can relate to setting parameter(s) of a used filter. For example, if a processed image seems to be textural (having high complexity), parameter(s) of a used filter can be adjusted to provide better edge/detail/texture preservation. For example, the parameter
Keeping these general principles in mind, we have to address several tasks:
What is a good (in the best case, optimal) input parameter (or a set of parameters)?
What is a good (proper, acceptable) output parameter (or a set of parameters) that allows to characterize the filtering efficiency adequately and to undertake a decision (on using filtering or not, on setting a filter parameter, etc.)?
How to get dependence between output and input parameters and how accurate it is?
These questions are partly answered below and the outcomes obtained in design and performance analysis of prediction techniques are described. We believe that a partial answer to the second question is the following. The ratio in expression (6) as well as the parameters
Based on the outcomes of the study [18], Abramov et al. in 2013 [17] observed that there is dependence between efficiency of filtering expressed by (6) and simple statistics of DCT-coefficients determined in 8 × 8 blocks. Two probability parameters have been considered. The first one denoted as
Examples of scatterplots and curve fitting into them for
The results of the study conducted in [17] have also shown the following. First, quality of fitting has to be characterized quantitatively. For this purpose, the approach [50] works well. It provides the parameter (coefficient of determination)
The conclusions drawn in [17] can be recalled here. First, the prediction of filtering efficiency for BM3D is less accurate than for the conventional DCT-based filter. This conclusion has been confirmed in later studies. This is associated with the use of two denoising mechanisms (DCT denoising and similar block search with their joint processing), where the latter mechanism has no connection to DCT statistics. Second, although the prediction accuracy for both
There are also observations understood later (in two recent years). First, there should be some restrictions imposed on the approximating function. For example, it is clear that the ratio in expression (6) cannot be negative. It is also clear that an approximating (fitting) function should be determined for all possible values of its arguments. Since the probabilities serve as arguments, they can vary from zero to unity. Meanwhile, arguments in both scatterplots in Fig. 2 vary in narrower limits. Besides, it could be good for curve fitting to have point arguments with approximately uniform density.
These requirements have been satisfied by using considerably more test images (including highly textural ones) and a wider set of noise standard deviations (including quite small ones). This has allowed obtaining scatterplot points for small
Examples of the obtained scatterplots and fitted curves for the DCT-based denoising are shown in Fig. 3. As it is seen, fitting is rather good and coefficient of determination is approximately 0.95 (see the details below). We believe these are already good results that allow practical recommendations. For example, it is clearly seen that there is no reason to carry out filtering if
Scatterplots of
Expressions for the obtained approximations for the DCT filter are as follows (we give only the functions of
The values of
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t0.978 | \n\t\t\t0.955 | \n\t\t
\n\t\t\t\t | \n\t\t\t0.963 | \n\t\t\t0.935 | \n\t\t
\n\t\t\t\t | \n\t\t\t0.82 | \n\t\t\t0.78 | \n\t\t
Goodness of fit (
It has been discovered that not only the mean of local (block) estimates of probability
where
The results of using multidimensional regression are presented in Table 2. The abbreviations used are the following:
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
DCT filter | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.963 | \n\t\t
\n\t\t\t\t | \n\t\t\t0.971 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.974 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.976 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.977 | \n\t\t||
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.848 | \n\t\t|
\n\t\t\t\t | \n\t\t\t0.923 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.926 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.927 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.928 | \n\t\t||
BM3D | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.95 | \n\t\t
\n\t\t\t\t | \n\t\t\t0.955 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.959 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.961 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.961 | \n\t\t||
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.845 | \n\t\t|
\n\t\t\t\t | \n\t\t\t0.905 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.905 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.909 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.917 | \n\t\t
Goodness of the best multiparameter fit for
The conclusions are the following. The use of more input parameters leads to larger (better)
More input parameters provide better prediction. At the same time, more time is needed for calculation of input parameters (although their calculation is not difficult). Then, a compromise solution could be the use of the dependence of the type
where
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
DCT filter | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.023 | \n\t\t\t6.338 | \n\t\t\t7.459 | \n\t\t
\n\t\t\t\t | \n\t\t\t2.225*10−4\n\t\t\t | \n\t\t\t10.81 | \n\t\t\t37.14 | \n\t\t|
BM3D | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.019 | \n\t\t\t6.591 | \n\t\t\t6.849 | \n\t\t
\n\t\t\t\t | \n\t\t\t5.324*10−5\n\t\t\t | \n\t\t\t12.42 | \n\t\t\t41.36 | \n\t\t
Coefficient values of the obtained approximations for
The expression (20) is not the only way to combine several input parameters into a joint output. Neural networks (NN) are known to perform this task rather well and to be good approximators [52]. This property has been used by us in [53] to make the neural network predict the considered metrics based on multiple input parameters. The obtained results are practically the same as in Table 3. Therefore, there is no need to use a more complex NN approximator instead of expression (20).
A more reasonable solution is to look for better input parameters. Such a study has been conducted in [51]. It has been shown that the probability
The obtained results for multiparameter fitting are presented in Table 4. The abbreviations are the same as in Table 2. The first observation is that even for one parameter (mean of local probabilities), the values
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
DCT filter | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.986 | \n\t\t
\n\t\t\t\t | \n\t\t\t0.989 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.989 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.989 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.99 | \n\t\t||
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.844 | \n\t\t|
\n\t\t\t\t | \n\t\t\t0.944 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.949 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.951 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.952 | \n\t\t||
BM3D | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.975 | \n\t\t
\n\t\t\t\t | \n\t\t\t0.977 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.978 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.978 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.978 | \n\t\t||
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.852 | \n\t\t|
\n\t\t\t\t | \n\t\t\t0.935 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.939 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.941 | \n\t\t||
\n\t\t\t\t | \n\t\t\t0.941 | \n\t\t
Goodness of the best multiparameter fit for
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
DCT filter | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.168 | \n\t\t\t10.8 | \n\t\t\t19.28 | \n\t\t
\n\t\t\t\t | \n\t\t\t0.01 | \n\t\t\t15.66 | \n\t\t\t144.3 | \n\t\t|
BM3D | \n\t\t\t\n\t\t\t\t | \n\t\t\t0.148 | \n\t\t\t11.33 | \n\t\t\t17.7 | \n\t\t
\n\t\t\t\t | \n\t\t\t0.004 | \n\t\t\t18.25 | \n\t\t\t161.7 | \n\t\t
Approximation coefficients values of obtained approximations for
Scatterplot of
Let us define the models of signal-dependent noise used. According to a first model [7], [11], the expression (1) transforms to
where
As mentioned in Section 2 (expression no. 15), the local threshold is set as
where
Some of the results of studies in our papers [54], [55] are presented next. One aspect that was specially addressed in these studies was to check the influence of an image set used in forming a scatterplot. In fact, two scatterplots have been formed separately: for the set of standard images used in optical image processing as Baboon, Barbara, Lena, etc., and for the set of images called “Remote Sensing” as Frisco, Diego, etc. The reason for such study was the following fact. Some people from RS community are categorically against using standard gray-scale test images in their studies although there are no commonly accepted sets of test RS images.
The methodology of obtaining scatterplot was modified a little. For the noise expression model (22), three different cases were modeled: prevailing influence of SI noise, dominant influence of SD noise, and comparable contribution of both components. As a result, a wide range of mean
Scatterplots of
Two examples of image processing are presented here. Fig. 6(a) represents the noisy image Frisco, where noise parameters are σ02=100;
For a real-life data, it is impossible to determine true values of the considered metrics characterizing filtering efficiency. However, it is possible to analyze the predicted values and denoising results visually. For fragments of sub-band images of hyperspectral sensor, Hyperion, such analysis was done. For example, noise parameters of the expression model (22) have been blindly estimated [11]. The noisy image for the 13th sub-band of the set EO1H1800252002116110KZ is depicted in Fig. 7(a). Noise is clearly seen. The prediction of
Noisy (a) and output (b) images Frisco
Noisy (a) and output (b) images of 13th sub-band images of Hyperion sensor
The sub-bands 13...22 are considered for two sets of Hyperion data. The values
Considering certain benefits achieved due to using
Scatterplots of
Additional studies concentrated on the multi-look SAR images that were corrupted by pure multiplicative noise [57]. Analysis has been done for speckle variance
Understanding that, in practice, noise can be spatially correlated [33], the case of spatially correlated noise – additive in [45] and multiplicative in [57] – are also studied. A difficulty of dealing with spatially correlated noise is that there are numerous shapes (and parameter sets) of 2D auto-correlation function or spatial spectrum of such a noise. Thus, studying a particular case of spatially correlated noise gives only limited information on general dependences. Hence, two models of spatially correlated noise (called middle correlation and strong correlation) have been considered [45]. A peculiarity of prediction is that the local estimate of probability
Scatterplot for
The scatterplots for middle-correlation noise and the fitted curves for
The scatterplots and fitted curves are presented in Fig. 10. The fitted curves are similar and they clearly show that there is no reason to filter images if
We have also studied the case of spatially correlated speckle [57]. It has been shown that the prediction seems possible for a spatially correlated noise. However, more research is needed to understand how to select a parameter or several parameters to characterize spatial correlation and how it can be involved in prediction.
Finally, a preliminary research has been carried out for denoising color images corrupted by AWGN with equal variance values in channels [58]. There are two differences in prediction. First, all DCT coefficients in 3D block are subject to analysis for estimating the local probabilities. Second, the metric PSNR-HMA [59], which is a color extension of PSNR-HVS-M, and improvement of this metric due to filtering similar to expression (8) have been used. In addition, instead of BM3D, its color version called C-BM3D has been analyzed [46].
The scatterplots and the fitted curves for
The scatterplots have been obtained and curves were fitted to them (see examples in Fig. 11). As mentioned earlier, filtering is useless for
Taking into account our previous experience, the multiparameter input was analyzed with exponential function expressed in (20). Considerable improvement has been reached, especially for
In this section, the compression of images corrupted by AWGN is considered. Lossy compression is carried out by the aforementioned coder AGU with
This section shortly describes how the scatterplots were obtained. As in the filtering case, a set of gray-scale test images of different content and complexity was used. AWGN of different intensity has been added and then the obtained images have been compressed by AGU. After this, the parameters (12) and (13) have been calculated as well as
The obtained scatterplot is presented in Fig. 12. A specific feature of this scatterplot is that it has negative values and they seem to be approximately −3.5 dB for
The scatterplot for the metric
The scatterplot and the fitted curves for
The scatterplot and the fitted curves for
Although prediction has been studied by simulations only for images corrupted by AWGN, it can also be applied to images corrupted by a signal-dependent spatially uncorrelated noise under condition that a proper VST is applied to them before compressing. Such VST (a generalized Anscombe transform in this case) provides approximately constant noise variance that usually equals to unity. Thus, QS = 4 is used. This approach has been used for Hyperion data and the results are presented in Fig. 14. There are two groups of sub-bands that are usually not analyzed in Hyperion data since they are too noisy. Thus, the prediction values are not given for all sub-bands. Analysis of the presented values shows that there are only a few sub-bands where it is worth expecting OOP. For most other sub-bands,
Fig. 15 shows the original and the decompressed images in 110-th sub-band, where decrease of visual quality according to quantitative criteria is predicted. Noise is not seen in the original image and the compression practically does not influence the image quality (in our opinion, both images look the same).
Predicted
The 110-th sub-band images before (a) and after (b) compression
A study [44] also presents data for three other DCT-based coders, where two of them are specially suited for providing better visual quality. It is demonstrated that the coder adaptive DCT (ADCT), which exploits the optimized partition schemes [60], provides certain improvements compared to AGU. Meanwhile, DCT coders oriented on improving the visual quality being applied to noisy images do not offer substantial benefits and, moreover, are even less efficient in many practical situations.
The methodology of predicting CR in OOP is the same as that for filtering. It is based on the scatterplot obtaining and curve fitting. The only difference is that the vertical axis relates to CR, while the horizontal axis, as earlier, corresponds to mean probability. Two mean probabilities
Two lossy compression methods, namely, the coders AGU and ADCT, have been studied. Their scatterplots are presented in Fig. 16. Contrary to other cases considered above, fitting is performed using a sum of two weighted exponential functions. As can be seen, fitting in both cases is very good with
We did not have real-life multichannel images corrupted by AWGN. But the hyperspectral data for the sensors Hyperion and airborne visible/infrared imaging spectrometer (AVIRIS) were available. Noise in them is signal dependent [14] with prevailing SD component for the model (22). The parameters of this noise were estimated in an automatic manner [11] and, thus, it became possible to apply VST (a generalized Anscombe transform with properly adjusted parameters) with converting noise into pure additive with unity variance.
Scatterplots and fitted curves of dependences of CR vs.
Results of a component-wise compression of Hyperion data (the analyzed set is EO1H1800252002116110KZ) (a) and AVIRIS Lunar Lake image (b) by the coder AGU after the generalized Anscombe transform
Lossy compression in OOP neighborhood has been applied after VST. After decompression, inverse transform has to be applied, respectively. The obtained and predicted values of CR for Hyperion data are depicted in Fig. 17(a). As can be seen, the curves are in good agreement. There are some channels where predicted CRs are slightly larger than attained ones. This is explained by the imperfectness of VST and blind estimation of noise parameters for channels with high signal-to-noise ratio. The largest CRs take place for sub-bands with low SNR (these are the sub-bands with indices 13–20, 125–130, and 175–180).
The results for the AVIRIS test image Lunar Lake are given in Fig. 17(b). Here, the agreement between the predicted and the attained values is even better than for the Hyperion data. Again, the largest CR is observed for sub-bands with low SNR. There are considerable differences in maximal and minimal values of CR. The main reason is the different SNR and different dynamic range in sub-band images. Certainly, CR also depends upon the image content.
It is demonstrated that it is possible to predict the efficiency of image filtering as well as the parameters of lossy compression of a noisy image in OOP neighborhood. As opposed to the earlier known approaches that allow predicting potential efficiency of filtering, the present approach predicts practically a reachable performance and makes this very rapidly, by one or more orders faster than filtering or compression itself.
Certainly, a limited number of quality metrics, filtering, and compression techniques have been considered. However, it is important that a general methodology of prediction is proposed, and it is shown there are somewhat strict connections between simple input parameters (that can be easily and quickly calculated) and output parameters that are able to adequately characterize the efficiency of filtering or lossy compression techniques. In favor of this methodology, there are certain facts. First, there are many modern filters that have filtering efficiency of the same order as the DCT-based filter and BM3D. Thus, predicting denoising efficiency for the filters mentioned above, it is possible to approximately predict performance for other modern filters (although such prediction would be less accurate). Second, the same holds for lossy compression methods. For example, AGU and JPEG2000 provide similar performance characteristics. Then, by predicting compression parameters for AGU, they are, in fact, estimated for JPEG2000 as well.
Concerning the decision making, whether to perform filtering or not, strict recommendations have been given for probabilities
The results of this research show that although sometimes the prediction of performance characteristics based on one input parameter is appropriately accurate, there are several means to improve the prediction accuracy. One way that deals with multiparameter input has been already used for particular cases. The use of mean
There are also other possible directions for future research. 3D filtering warrants a more thorough study, at least, for the case of more than three channels. The same relates to 3D lossy compression performance, which has not been tried to predict yet. Compression parameters for QS other than the one recommended for OOP is also of sufficient interest in DCT-based lossy compression. Influence of errors in
Alzheimer’s disease (AD) is a brain disorder described in 1906 by Aloes Alzheimer, a German physician [1]. It is a progressive and neurodegenerative disorder which mainly occur in old aged people of over 65 years of age [1, 2, 3]. For progression and development of disease various pathways are involved such as formation of plaque, inflammatory cascade, cholinergic deficit, oxidative stress, and many more. Senile plaques formation and neurofibrillary tangles persist significant neuro-pathological symbols of this disease. Senile plaques are the main component of amyloid beta (Aβ) peptide that are covered by dystrophic neurites and activated microglia. Accumulation of Aβ results changed process of proteolytic amyloid precursor protein (APP) through beta and gamma secretase. The β-amyloid peptide, with 39–42 amino acid residues (BAP), perform vital role in development of AD. There are mainly two types of AD, familial AD which affects the people who have age less than 65. The other type of AD is sporadic AD which affect the people older than 65. At present there is no cure for Alzheimer’s disease but it could me managed to some level by using available medications (Table 1) [4, 5].
Factors | Dementia | Alzheimer’s disease | Normal aging |
---|---|---|---|
Definition | CNS disorder due to disease or any other pathological condition. | Common form of dementia. | Condition occur due to programmed cell death with time (gene therapy) and causes various disability. |
Cause | AD, stroke, thyroid issues, vitamin deficiency, etc. | Deposition of beta amyloid protein in brain. | May cause biological systems to fail (DNA oxidation, DNA methylation, and apoptosis). |
Duration and age | Permanent damage and 65 years and olders. | Average 8–20 years and 65 year but can occur as early as 30s. | Gradual and progressive condition until death. |
Symptoms | Issues with memory, poor judgment, less focus and attention. | Difficulty to remembering newly learned information. | Bone break more easily, decrease overall energy, greater risk of heart stroke or hypothermia. |
In 2020 approx. 50 million individual dealing with dementia worldwide. In India more than four million of people suffering from AD and dementia while in USA approx. 5.8 million living with dementia and AD. It is estimated that it is the fifth main source of death in USA and the number of death increased 146% between 2000 and 2018. It is predicted the causality will increase to 13.8 million which number of patient increases to 13.5 million by 2050. Elderly persons are more prone to younger one [8].
In maximum case genetic lifestyle choices aging stress and environmental factors induces AD [9].
Researchers have claimed that older adults have more risk of having AD. Scientists are still learning, how age-related changes in the brain may harm neurons and contribute to Alzheimer’s [10].
It occur due to mutation in chromosome 1, 14, and 21. The changes on chromosome 1 produces PRESENILIN-2 (PSEN2) named protein while chromosome 14 produces PRESENILIN-1 (PSEN1). These PSEN 1 and PSEN 2 directly and indirectly both trigger/encode for membrane protein convoluted for amyloid precursor protein. These mutations reduce the effectiveness of γ-secretase, an enzyme which is responsible for formation of beta amyloid peptide (βAP) [11]. Amyloid precursor protein is coded on chromosome 21 and this mutation results in overproduction of beta amyloid peptide. Mutation on chromosome 1, 14, and 21 results in early onset AD [12].
Apo-lipoprotein E (APOE) gene is responsible for late onset AD. APOE gene is lipid metabolism regulator which have an affinity for beta amyloid protein and increases the risk of AD. Chromosome 19 produces APOE gene. The inheritance of APOEe4 allele own genetic risk in sporadic AD. APOEe4 allele, age elevate the risk for development of late AD by two to three folds and two copies of five folds [13].
Variations in gene for receptor sortilin, SORT1, that is important for transferring APP from surface of cell to Golgi-endoplasmic reticulum complex, have been found in familial and sporadic types of AD [14].
Conditions such as heart disease, stroke, high blood pressure, diabetes, and obesity are also linked as risk factors for AD [15].
The real origin of this disease is not well known but problems are linked with brain protein that work abnormally and cause malfunction. As a result neurons were damaged then fail to connect other neuron as a result they die. Initially the degradation starts within the region of brain which control memory ultimately dementia occur (Figure 1) [16].
Clinical findings in Alzheimer’s disease [
In the initial stage of AD amyloid proteins works abnormally and cause overproduction of beta amyloid secretase named enzyme split amyloid processor protein and due to deviation from this process, especially sudden change in gamma and beta secretases leads to unnatural production of amyloid beta [18].
Tau protein is known for its stabilizing property. It is useful in the transportation of nutrients and others essential matter within the neurons while in AD. Tau protein cause mutation and changes its structure which is known as neurofibrillary tangles [18, 19].
It is observed in the patient of AD there is deficiency of ACh due to abnormal functioning of choline acetyl transferase. This will treat as a clinical hallmark to support cholinergic hypothesis there is also a possible treatment of AD by increasing the level of ACh by reducing the activity of AChE cholinergic depletion observed after neurodegenerative cascade various cholinesterase inhibitors currently used in the treatment of AD [20].
It is defined as the excess interaction of neurotransmitter glutamate and other excitatory neurotransmitter which may act as a potent neurotoxins for Alzheimer [21].
Apo-lipoprotein E play important role in the cholesterol transportation and catabolism of triglyceride lipoprotein. Cholesterol also alter the clearance of amyloid beta and generation of NFT in neuronal membrane APOE4 also enhance the deposition of beta amyloid protein. High level of cholesterol in brain there by alter the member functioning this leads to plaque formation resulting AD [22].
Oxidative stress is generated due to imbalance of ROS generation and its quenching. Brain is more prone for oxidative stress due to high consumption of O2. High level of polyunsaturated fatty acid. Low level of antioxidants and high level of redox transition metal ions. These all factors facilitate the production of reactive oxygen species like superoxide, hydrogen peroxide, etc. These ROS interact with surroundings proteins nucleic acids, etc. and cause cellular dysfunction [23]. There is also a close relationship between amyloid beta and oxidative stress because amyloid beta elevate the formation of ROS and initiate mitochondrial damage. This will also cause oxidative damage. These effects can also be observed in brain of triple transgenic mouse model of AD where tocopherol and GSH level decrease while lipid peroxidation is increased [24]. However this was observed before any plaque formation. While in another model dual mutant APP was expressed, oxidative stress and inflammation was induced by thiamine deficiency provoke plaque formation and enhance the level of amyloid [25].
It is observed in the marphotric analysis of AD patients brain showed significant deficiency of mitochondria while its DNA and protein concentration elevate in cytoplasm and in the vacuoles associated with lipofuscin [26]. These mitochondria may be damaged due to autophagy and oxidative stress. Mitochondrial cytochrome oxidase activity also reduced in cortical region of AD brain. Due to this deficiency mitochondrial dysfunction occur and ROS generated and energy stores were decreased and ultimately neurodegeneration occur [27].
Evidence from animal and human studies support functional roles of sex hormones like estrogens, progesterone, and androgens in behavior and cognition. With several neuroprotective activity involved, age reduces level of sex hormones were connected with greater possibilities of cognitive degeneration and AD. For example, in females development of AD is associated with decreased exposure to estrogens across the lifetime, while in males age related degeneration in both levels of peripheral and brain testosterone is linked with greater susceptibilities of AD development. Also, alterations in receptors of sex hormone and downstream signaling pathways during aging have been stated. For example, the nonfunctional splicing estrogen variants receptor alpha in the hippocampus was enhanced throughout aging and AD, with advanced levels in female old age subjects in comparison to males. Moreover, studies recognized polymorphisms of estrogen receptors related with intellectual decay and AD development in females, especially in APOE ε4 (APOE4) transporters. These information recommended diminished responsiveness of brain to sex hormones during aging and disease development. However, clinical trial outcomes of sex hormone therapy in AD are rather contentious. Despite prior studies associating protective activity of estrogen replacement against AD in females, huge clinical studies failed to exhibit any useful possessions. It was suggested that replacement of hormone initiation in the serious window of perimenopause may diminish the risks of dementia, while it might raise the risks if started a very long time after menopause. Moreover treatment timing, reduced responsiveness at receptors of brain and downstream signaling pathways might add to the uselessness of hormonal therapy. Together, these investigations recommend the complication of sex hormones association in AD [31].
Currently there is no cure for this disease, the objective of several medicine is used to reduce symptoms linked with disease and to reduce disease progression (Table 2) [32, 33, 34, 35, 36].
Drug name | Indication | Mode of action | Adverse effect |
---|---|---|---|
Donepezil | Minor to chronic | It stops the breakdown of ACh by preventing the function of acetyl cholinesterase | Fatigue, abnormal dreams, hallucinations, confusion, hypertension, abdominal pain |
Treats intellectual indication of AD | |||
Galantamine | Minor to medium | Stops the breakdown of Ach and stimulates receptors to discharge extra ACh | Somnolence, bradycardia, insomnia, urinary tract infection, anorexia, syncope |
Treats intellectual indication of AD | |||
Rivastigmine | Minor to medium | Stops the breakdown of Ach by preventing the enzymes that abolish ACh | Dizziness, diarrhea, anxiety, vertigo, asthenia, tachycardia |
Also used to treat dementia from Parkinson’s disease | Treats intellectual indication of AD | ||
Memantine | Medium to severe | Blocks glutamatergic (NMDA) receptors and controls the action of glutamate | Headache, constipation, vomiting, backache |
Treats intellectual indication of AD | |||
Donepezil/memantine | Medium to severe | it binds to NMDA receptor-operated caption channels, and gives therapeutic effects by preventing persistent stimulation in CNS | Hallucination, headache, cough, fatigue, cramping, syncope, increased frequency of bowel movements |
Currently used drug for the treatment of Alzheimer’s disease.
From the previous eras, the pharmaceutical industry has decided to chiefly focused on the amyloidocentric method, dedicating significant possessions to form useful AD drugs. Nevertheless, numerous failures of drug candidates in clinical trials have led investigators to question the viability of this approach [10, 11, 12]. Possible cause for failure is a absence of biomarkers that could consistently recognize AD in comparatively initial phases. It is totally promising that the patients presently enrolled for phase III trials are in such advanced phases of AD that any attempted interference is possibly inadequate. In the meantime, there is still a number of new management under development, that focused the amyloidogenic route. In order to decrease generation of Aβ from the APP, inhibition of γ- and β-secretase and the potentiation of activity of α-secretase have been deliberated.
β-secretase enzyme complex contributes in the primary phases of the amyloidogenic APP-processing pathway. The inhibitors of β-secretase development is a task because, besides the APP, this complex has several substrates. To give just one example, neuregulin-1, that included in the CNS axons myelination and synaptic elasticity, is a target β-secretase. Substrates wide range results to substantial adverse effects, even if the precise enzyme inhibition is reached. But, E2609 (clinical trial ID# NCT01600859), MK-8931 (NCT01739348), and LY2886721 (NCT01807026 and NCT01561430) have all exposed efficiency in decreasing the production of Aβ by up to 80–90% in the cerebrospinal fluid (CSF) in humans. None of inhibitors of β-secretase have touched the market so far [37, 38, 39, 40].
In the final stage of amyloidogenesis, γ-secretase complex is responsible for the production of Aβ(1–40) and Aβ(1–42). Inhibition of γ-secretase was firstly proposed strategy for the management of Alzheimer’s disease but the substrate promiscuity shows equal issues facing γ-secretase inhibitors. γ-secretase proposed to target the Notch protein which is responsible for the regulation of cell proliferation, development, differentiation and cellular communication but off target secondary effects are major concern [41, 42, 43].
Semagacestat (LY450139) named γ-secretase inhibitor reduces the Aβ level in the blood and in cerebrospinal fluid [44]. The results obtained from the clinical study conducted on 3000 patients shows the major adverse effects like decrease cognition abilities and difficulty in the carry out daily living activities and elevated skin cancer incidence and increased risk of infection and weight loss. Another γ-secretase named avagacestat discontinued in the development stage due to lack of efficacy (NCT00810147, NCT00890890, NCT00810147, NCT01079819, [45, 46, 47]).
Several nonsteroidal anti-inflammatory drugs like indomethacin, ibuprofen, flurbiprofen, sulindac also decreases the Aβ(1–42) peptide levels in in-vivo and in in-vitro studies. Ibuprofen is a cyclooxigenase inhibitor while R-flurbiprofen (tarenflurbil) is not, so the reduction of Aβ(1–42) peptide levels is not associated with the COX inhibition. Unfortunately, in clinical trials tarenflurbil and ibuprofen does not shows efficacy for the treatment of Alzheimer’s disease. The idea of long term use of NSAID’s for the treatments of Alzheimer’s disease as NSAIDS reduces the Aβ peptide level in blood but negative results reported in the clinical studies that’s why this hypothesis requires further investigations [48, 49].
Clinical studies with 8-hydroxiquinolines compounds like clioquinol and PBT2 also conducted for the treatment of Alzheimer’s disease. The mechanism of action is yet established, but the expected MOA suggested that the increased levels of oxidative stress is due to the copper ions binding to Aβ, leading to metal-mediated generation of ROS (reactive oxygen species). It is proposed that the 8-hydroxiquinolines may prevent Aβ aggregation and restoring homeostasis in the cellular levels of copper and zinc ions. But after in clinical development these compounds failed due to lack of efficacy [50, 51, 52].
Another possible treatment choice that is involved on the amyloidogenic pathway is to stimulate the existing amyloid aggregates clearance. To achieve this, three different approaches have been assessed.
Amyloid plaques are destroyed by various proteases comprising neprilysin, IDE, plasmin, angiotensin converting enzyme, endothelin converting enzyme, and metalloproteinases. Levels of protein these enzymes reduces in AD, that promotes accumulation and formation of Aβ. Despite being an attractive approach for forming disease-modifying medicine, no compounds with this MOA have ever entered advanced clinical development because of lack of specificity.
Transport of Aβ between the circulation of CNS and peripheral is controlled by: (i) apolipoproteins (e.g., Aβ might be transported from the blood to the brain when it is bound to APOE); (ii) low-density lipoprotein receptor-related protein (LRP-1), that enhances Aβ discharge from the brain to the blood; (iii) receptor for progressive glycation end products (RAGE), that enables the Aβ transport across the blood-brain barrier (BBB) [53, 54].
Any treatment goal, that is determined on this mechanism, is to decrease the load of cerebral amyloid by trying to control Aβ to the peripheral circulation. To this end, a different number of approaches have been suggested, particularly the administration of LRP-1 peripherally. Though, the only drug candidates that have entered the clinical phase are the RAGE inhibitors.
Immunotherapy approach designed to stimulate clearance of Aβ with the aimed of decreasing load of amyloid load in AD. Active immunization (vaccination) with either Aβ(1–42) (main form found in senile plaques) or other synthetic fragments has been positively assessed in transgenic mouse models of AD. Human tests were primarily hopeful; though first-generation vaccine (AN1792) treatment has shown major adverse events which results to the phase II trials cessation. AN1792 contained of a synthetic full-length Aβ(1–42) peptide with a QS-21 adjuvant. Because of a T cell-mediated autoimmune response, 6% of patients have established inflammation in brain that ended up being aseptic meningoencephalitis [55].
Second-generation vaccines were planned utilizing a limited portion of Aβ(1–6) peptide in an try to inhibit nonspecific immune response seen with the full-length vaccine. Novartis designed CAD 106, was the first second-generation vaccine which moved to development phase. Newly finished phase II trial have exposed a Aβ-specific antibody response in 75% of treated patients, without producing any side effect. Janssen developed ACC-001, has freshly finished two-phase II trials (NCT01284387 and NCT00479557) with an additional phase II trial still continuing (NCT01227564). Though, the pharmaceutical industry has canceled the ideas for this vaccine development. Further vaccines, comprising tetra-palmitoylated Aβ(1–15) re-formed in a liposome (ACI-24), MER5101 and AF205 are now in different phases of preclinical progression [56, 57, 58].
It is the monoclonal or polyclonal antibodies administration directed against Aβ. This treatment contains intravenous administration of anti-Aβ antibodies to the patient. The advantage of this approach is to match to active immunization is which the proinflammatory T cell-mediated immune response should not arise. Reports have shown that in transgenic animals passive immunization decreases the load of cerebral amyloid and recovers cognition, even when the amyloid plaque numbers are not suggestively decreased. This could be recognized to the soluble amyloid oligomers neutralization, that progressively identified to play an important role in the pathophysiology of AD.
Bapineuzumab and solanezumab are two monoclonal antibodies which are reach now present in advanced phase of development. Though, two phase III trials had failed in 2012 due to low effectiveness in patients with mild-to-moderate AD [59]. Both are humanized monoclonal antibodies against Aβ(1–6) and Aβ(12–28), respectively. In bapineuzumab, noteworthy decrease in brain amyloid plaques and phosphorylated Tau in cerebrospinal fluid was stated. Though, the treatment unsuccessful to give noteworthy developments of brain function. In a solanezumab trial, infusions of 400 mg of solanezumab or placebo were given for 80 weeks once a month in patients with mild-to-moderate AD. The outcomes recommended that solanezumab might recover cognition in mild AD; but statistical significance was not attained in study. Presently solanezumab present in phase III trials in patients with AD (NCT01127633 and NCT01900665) and in older persons who have common thinking and memory function but who might be at danger of AD developing in the future (NCT02008357, [60, 61]).
Crenezumab (MABT5102A) is a humanized monoclonal antibody that uses IgG4 backbone. In April 2014 a stage II trial to measure the safety and effectiveness in patients with mild-to-moderate AD (NCT01343966) was accomplished, while the outcomes are not yet openly accessible. The supreme stage II trial pointing to assess the safety and effectiveness of crenezumab in asymptomatic transporters of E280A autosomal-dominant mutation of PSEN1 initiated in November 2013 (NCT01998841).
Other monoclonal antibodies against Aβ established so far contain PF-04360365 (ponezumab) that targets the free carboxy terminal amino acids 33–40 of the Aβ peptide; MABT5102A, that binds to Aβ monomers, oligomers, and fibrils with similarly great affinity; GSK933776A, that is likewise to bapineuzumab in which it binds to the N-terminal Aβ(1–5). Additional, other passive immunotherapies typically in stage I clinical trial involve NI-101, SAR-228810, and BAN-2401 [58, 62].
In neurons Tau proteins are extremely soluble and abundant where they play a important role in stabilization of microtubule, mainly in axons [63]. Tau hyperphosphorylation resulting the insoluble paired helical filaments (PHF) development that form neurofibrillary tangles. The microtubule-binding capacity damage initiate destabilization of cytoskeleton, that ultimately develops neurodegeneration and neuronal death [64]. As a substitute to amyloidocentric strategies, this treatments goal to prevent the phosphorylation of Tau protein. Additional, microtubule-stabilizing drugs can be utilized as a disease-modifying approach in AD. In current years, immunomodulation was recommended as a feasible choice for stimulating operative Tau aggregates clearance [65].
All Tau proteins are a result of different splicing of a microtubule-associated protein Tau (MAPT) gene. Primary mechanism that controls Tau binding to microtubules is phosphorylation. The protein remains soluble under physiological circumstances; though, in this disease, pathological hyperphosphorylation of Tau compromises its regular functions [66, 67]. Imbalance between the catalytic activity of kinases and phosphatases occurs hyperphosphorylation. Enhanced expression of active forms of several kinases in the areas proximal to neurofibrillary tangles has been labeled in AD, comprising CDK5, GSK3β, Fyn, stress-activated protein kinases JNK and p38, and mitogen-activated protein kinases ERK1 and ERK2 [68]. Certain kinases promote continuation of tau phosphorylation in neurofibrillary tangles. Resulting, noteworthy research determinations have been dedicated to the kinase inhibitors development as a probable treatment approach for AD. For example, SP600125, a extensively utilized pan-JNK inhibitor, employs valuable effects on cognition and decreases neurodegeneration in an APP/PS1 transgenic mouse model of AD. It has been planned which precise inhibition of JNK3 can be adequate to carry comparable benefits as seen with SP600125 in rodent models. Human data in AD patients designate a positive correlation between the JNK3 and Aβ(1–42) levels in the brain. Moreover, JNK3 upregulation was distinguished in the CSF and was related with loss of memory. Consequently, inhibition of JNK3 remains a capable goal for future treatments [69, 70, 71].
Tau hyperphosphorylation contribute to neurotoxicity detected in AD brain. Methylene blue dye derivatives have revealed certain potential Tau aggregates formation inhibition. Methylene blue disturbs the Tau aggregation, has the capability to prevent amyloid aggregation, recovers the effectiveness of mitochondrial electron transport chain, decreases oxidative stress, stops mitochondrial impairment, and is also an autophagy modulator. The first-generation molecule resulting from methylene blue (Rember) seemed to stabilize AD development in a clinical trial that continued 50 weeks. These outcomes encouraged investigators to form a next-generation form of methylene blue, TRx 0237. This agents is a purified derivative of methylene blue that not only prevents aggregation of Tau protein but also liquefies brain tau aggregates. Various trials are presently ongoing (NCT01626391, NCT01689233, NCT01689246, NCT01626378) to assess the possible effectiveness of this agent in AD [72, 73].
Stabilization of microtubule might possibly attain a comparable end-result as which seen with the Tau hyperphosphorylation inhibitors. Paclitaxel is a microtubule-stabilizing agents presently in utilize in the oncology arena. Inappropriately, this agents is unable of BBB crossing and its utilize is related with major adverse events, that limits its efficacy in AD. In addition to paclitaxel, other microtubule-stabilizing agents like TPI 287 have been measured as a probable AD remedy. TPI 287 is a derivative of taxane, also utilize in the treatment of cancer. TPI 287 alleviates the microtubules by binding to tubulin. NCT01966666 trial will estimate TPI-287 safety, pharmacokinetic possessions, and tolerability by intravenous infusion in mild-to-moderate AD.
Epothilone D is a microtubule-stabilizing agent that enhanced axonal transport, decrease axonal dystrophy, reduced Tau neuropathology, and decreased hippocampal loss of neuron; though, in 2013 drug development for AD was discontinued after an unsuccessful clinical trial. With respect to Tau, more research are essential in order to better understand the exact molecular mechanisms elaborate in neurotoxicity of Tau. Current research associating the neurotoxic profiles of different forms of Tau recommend which is a soluble form is probable the greatest toxic. Thus, future therapeutic approaches should be focused on aiming Tau soluble forms [74].
Just as with the immunotherapies aiming Aβ, both passive and active immunization approaches against Tau have been measured. It was established that decrease in formation of Tau aggregate and enhanced Tau oligomers clearance and insoluble aggregates could all be reached with either active or passive immunotherapies. In rodents, treatment with monoclonal antibodies directed against hyperphosphorylated Tau has results to improvements in cognition and was not connected with noteworthy side effects.
Axon neuroscience began a stage I trial in 2013 to estimate the safety and tolerability of AADvac-1, an active immunotherapy that contains synthetic peptide derived from the Tau sequence coupled to keyhole limpet hemocyanin; the precise molecular nature of the antigen has not been disclosed (NCT01850238 and NCT02031198). AADvac-1 uses aluminum hydroxide as an adjuvant. At the 2014 Alzheimer’s Association International Conference (AAIC) in Copenhagen, good preclinical safety profile was reported for the treatment period of up to 6 months in rats, rabbits, and dogs. These initial outcomes are hopeful and it remains to be seen whether AADvac-1 will prove satisfactory safety and efficiency in patients [75, 76].
The hippocampus, the chief region of brain elaborate in memory processing, is influenced by modulation of cholinergic neurotransmitter. One of the well categorized irregularities linked with neurotransmitter deviations is the cholinergic neurons degeneration in the nucleus basalis of Meynert and the cholinergic inputs loss to the neocortex and hippocampus. Various studies reported reduced in choline acetyltransferase (ChAT), acetylcholine (ACh) release, as well as decreases in nicotinic and muscarinic receptors in the cerebral cortex and hippocampus of postmortem AD brains. Acetylcholinesterase inhibitors (AChEI), one of the only two classes of compounds that presently accepted for AD treatment, act by stimulating ACh bioavailability at the synapse. Inappropriately, none of these agents are proficient of withdrawing the course of AD nor of even noticeably reducing down the degree of disease development. Their clinical effect is basically palliative; though, their possible utilize in combination therapy with other disease-modifying agents should not be omitted [77, 78].
As revealed by clinical study data and research articles that diabetes is a one of the key factor that leads to AD pathology and unfolds the close connection between insulin-deficient diabetes and cerebral amyloidosis. These data also suggests about insulin signaling impairments (both peripheral and central) is possibly be existing in both diseases. Hence, considering insulin hormone at the core, “type 3 diabetes” hypothesis of AD was developed, observing metabolic phenotypes into a coherent framework [79].
The most anticipated mechanisms for the development of AD due to diabetes could be: glucose toxicity, insulin resistance, oxidative stress, elevated levels of advanced glycation end products, and cytokine-mediated neuroinflammation. Recently, Clarke and colleagues demonstrated that neuroinflammatory cascades can be initiated by the administration of soluble hypothalamic Aβ oligomers that ultimately causes disturbances in peripheral glucose homeostasis. Tumor necrosis factor α (TNFα) may have a significant role during this process [80].
Rosiglitazone and pioglitazone are used as antidiabetic drugs, which regulate glucose homeostasis by increasing insulin sensitivity, reducing blood glucose levels, and improving lipid metabolism. Both compounds have also been studied as potential therapeutics for AD treatment, with reported improvements in mitochondrial oxidative metabolism [81]. In animal models, pioglitazone modified various indices of brain aging but did not slow down the cognitive decline. Rosiglitazone and pioglitazone also induce the expression of peroxisome proliferator-activated receptor-γ co-activator 1 alpha (PGC-1α), a molecule that plays multiple roles in mitochondrial biogenesis, energy metabolism, and mitochondrial antioxidants expression. Previous studies have demonstrated that, in the human brain tissues, the expression of PGC-1α decreases with progression of AD dementia. Thus, PGC-1α upregulation may improve the mitochondrial energy metabolism and AD pathology [82, 83, 84, 85, 86].
In a small scale clinical trial on mild-to-moderate AD patients, it was found that pioglitazone enhances memory and cognition. On the other hand clinical trial (phase II) with larger group of patients (who did not possess an ApoE4 allele) were on treatment with rosiglitazone (6 months) shows improvement in memory retention and attention. However, similar study (phase III trial) using rosiglitazone failed to show efficacy in AD (NCT00550420). It is important to note that rosiglitazone was administered at much lower dosage than required to exert efficacious effects on AD pathophysiology in these trials, in rodent models of the disease. NCT00348140 recently completed clinical trial in which rosiglitazone was administrated in combination with AChEIs in patients with AD (mild-to-moderate) and until now no further outcome yet reported.
As a treatment possibility for AD, intranasal insulin have also been considered as it bypasses the BBB easily; adding the advantage of possibly minimum adverse events in peripheral tissues. Theoretically it is well established that direct delivery of insulin to the brain will activate cerebral insulin signaling leading to enhancements in memory processing resulting into neuroprotection. A recent ongoing clinical trial (with NCT017679090 is assessing long-term (12 months) efficacy of intranasal insulin (Humulin R U-100) among mild AD patients [87].
Also, it has been found that reduced plasma amylin concentrations may contribute in the progression of AD. As revealed by transgenic animal models of AD, amylin and pramlintide (amylin analog) reduced the brain Aβ levels and advances cognition. Interestingly, amylin inhibits β-secretase, whereas pramlintide did not [88].
Here is the number of herbal plants reported to might have anti-Alzheimer activity (Table 3).
Sr. No. | Work done | Plant used | Common name | Author | Year | Ref. |
---|---|---|---|---|---|---|
1. | Effects of the hydroethanolic extract of | Fir clubmoss | Valu et al. | 2021 | [89] | |
2. | Evaluation of traditional herb extract | Sage | Datta et al. | 2020 | [90] | |
3. | Protective effects of tenuifolin isolated from | Yuan zhi | Wang et al. | 2019 | [91] | |
4. | Shankhapushpi | Kizhakke et al. | 2019 | [92] | ||
5. | Cheeseweed | Jiménez et al. | 2019 | [93] | ||
6. | Antioxidant, anti-Alzheimer and anti-parkinson activity of | Indian wormwood | Pal and Pradeep | 2018 | [94] | |
7. | Antioxidant and anti-acetylcholinesterase activities of essential oils from garlic ( | Garlic | Akinyemi et al. | 2018 | [95] | |
8. | Nootropic activity of ethanolic extract of | Ankol | Parameshwari et al. | 2018 | [96] | |
9. | Drumstick tree | Mahaman et al. | 2018 | [97] | ||
10. | Ameliorative effect of | Shonna cabbage | Manasa et al. | 2017 | [98] | |
11. | Evaluation of nootropic activity of green peas in mice | Green peas | Kaura et al. | 2017 | [99] | |
12. | Ameliorative effect of | Celery | Phetcharat et al. | 2017 | [100] | |
13. | Evaluation of effect of alcoholic extract of | Guduchi | Jyothi et al. | 2016 | [101] | |
14 | Effect of | Green tea | Mahmoodzadeh et al. | 2016 | [102] | |
15. | Evaluation of nootropic activity of | Turmeric | Reddy et al. | 2015 | [103] | |
16. | Effect of ethanolic seed extract of | Orchid tree | Nemalapalli et al. | 2015 | [104] | |
17. | Mora | Kim et al. | 2015 | [105] | ||
18. | Anticholinesterase and antioxidant properties of aqueous extract of | Cola nut | Oboh et al. | 2014 | [106] | |
19. | Antiamnesic effect of piracetam potentiated with | Aamla | Ramachandran et al. | 2013 | [107] | |
20 | Antiamnesic activity of | Jamun | Alikatte et al. | 2012 | [108] | |
21 | Acetylcholine and memory-enhancing activity of | Cluster fig | Faiyaz et al. | 2011 | [109] | |
22 | Protective effect of | Noni | Muralidharan et al. | 2010 | [110] |
Plants studied in Alzheimer’s disease.
In 2021 USFDA approved
It was approved for medical use in the United States. Aducanumab has since been approved by the Ministry of Health and Prevention in the United Arab Emirates as of October 3, 2021, making it the second country in the world to approve the treatment.
It is suggested for mild cognitive impairment (MCI) or mild dementia stage of Alzheimer’s disease [112, 113].
Here is the figure that shows the agents which is in developing stage involve in the trials for the management of Alzheimer’s disease. Most of agents in the trial target disease modification [114] (Figure 2).
Drugs in clinical trials for treatment of Alzheimer’s disease in 2021. In which the shape of icons shows the population involve in trials; the outer ring shows drugs in Phase I; the middle rings shows drugs in Phase II; the inner most ring shows drugs in Phase III trials [
In which the shape of icons shows the population involve in trials; the outer ring shows drugs in phase I; the middle rings shows drugs in phase II; the inner most ring shows drugs in phase III trials [115].
Alzheimer’s disease is serious brain disorder, at present there is no cure for this disease but currently it can be controlled by using a drugs which symptomatically treat AD. AChE inhibitors are the first approved anti-AD drugs by the FDA, and they are also the first and the most useful drug used in the clinical treatment of AD. But now few of drugs also approved by USFDA in 2021 for the treatment of AD and few also in the trial phase. Results from clinical studies have shown different new drugs in pipeline and various novel approaches may also beneficial for treating AD. Interests in the utilization of different herbal products also increase day by day. This study provides the details about recent advancement the medicinal plants against the Alzheimer’s disease. Availability of these new medicinal plants for AD will further increase the treatment options and thus provide a significant benefit to patients who remain uncontrollable to existing therapy.
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Bouallègue, J. Haggège and M. Benrejeb",authors:[{id:"141915",title:"Dr.",name:"Soufiene",middleName:null,surname:"Bouallegue",slug:"soufiene-bouallegue",fullName:"Soufiene Bouallegue"}]},{id:"39435",doi:"10.5772/48529",title:"Fuzzy Control Systems: LMI-Based Design",slug:"fuzzy-control-systems-lmi-based-design",totalDownloads:4673,totalCrossrefCites:6,totalDimensionsCites:7,abstract:null,book:{id:"2229",slug:"fuzzy-controllers-recent-advances-in-theory-and-applications",title:"Fuzzy Controllers",fullTitle:"Fuzzy Controllers - Recent Advances in Theory and Applications"},signatures:"Morteza Seidi, Marzieh Hajiaghamemar and Bruce Segee",authors:[{id:"145408",title:"Mr.",name:"Morteza",middleName:null,surname:"Seidi",slug:"morteza-seidi",fullName:"Morteza Seidi"},{id:"147329",title:"Ms.",name:"Marzieh",middleName:null,surname:"Hajiaghamemar",slug:"marzieh-hajiaghamemar",fullName:"Marzieh Hajiaghamemar"},{id:"155198",title:"Dr.",name:"Bruce",middleName:null,surname:"Segee",slug:"bruce-segee",fullName:"Bruce Segee"}]},{id:"39429",doi:"10.5772/47798",title:"A Type-2 Fuzzy Model Based on Three Dimensional Membership Functions for Smart Thresholding in Control Systems",slug:"a-type-2-fuzzy-model-based-on-three-dimensional-membership-functions-for-smart-thresholding-in-contr",totalDownloads:3345,totalCrossrefCites:2,totalDimensionsCites:6,abstract:null,book:{id:"2229",slug:"fuzzy-controllers-recent-advances-in-theory-and-applications",title:"Fuzzy Controllers",fullTitle:"Fuzzy Controllers - Recent Advances in Theory and Applications"},signatures:"M.H. Fazel Zarandi, Fereidoon Moghadas Nejad and H. Zakeri",authors:[{id:"142009",title:"Prof.",name:"Mohammad Hossein",middleName:null,surname:"Fazel Zarandi",slug:"mohammad-hossein-fazel-zarandi",fullName:"Mohammad Hossein Fazel Zarandi"},{id:"160785",title:"Ph.D.",name:"H",middleName:null,surname:"Zakeri",slug:"h-zakeri",fullName:"H Zakeri"},{id:"160872",title:"Prof.",name:"Freeidon",middleName:null,surname:"Moghadas Nejad",slug:"freeidon-moghadas-nejad",fullName:"Freeidon Moghadas Nejad"}]},{id:"52178",doi:"10.5772/64951",title:"Adaptive Building Envelope: An Integral Approach to Indoor Environment Control in Buildings",slug:"adaptive-building-envelope-an-integral-approach-to-indoor-environment-control-in-buildings",totalDownloads:2112,totalCrossrefCites:5,totalDimensionsCites:4,abstract:"The problem of energy consumption of buildings is complex and multidimensional, as it is a cross section of building envelope performance, indoor environmental conditions and user demands and preferences. In order to fulfil the EU goal stated in the 2020 climate and energy package and beyond, the implementation of high-performance buildings is crucial. Part of the solution is properly designed, flexible and adequately controlled building envelope that can contribute to reduced energy consumption and to increased occupancy comfort. In the presented chapter first, a structured treatment of the indoor environment formation is proposed that can be used in order to define appropriate fields of interventions when designing building automation systems. Furthermore, interaction between adaptive building envelope elements, indoor and exterior environment is discussed and elaborated. Second, the conventional and artificial intelligence control approaches used in building automation are discussed and commented, whereas advantages and disadvantages of each group are discussed. At the end, an example of building automation system designed on the principles of a holistic treatment of indoor environment in buildings is presented. The discussed system was designed at the Faculty of Civil and Geodetic Engineering using a combination of conventional and artificial intelligence control methods.",book:{id:"5238",slug:"automation-and-control-trends",title:"Automation and Control Trends",fullTitle:"Automation and Control Trends"},signatures:"Mitja Košir",authors:[{id:"182476",title:"Dr.",name:"Mitja",middleName:null,surname:"Košir",slug:"mitja-kosir",fullName:"Mitja Košir"}]}],mostDownloadedChaptersLast30Days:[{id:"39423",title:"Output Tracking Control for Fuzzy Systems via Static-Output Feedback Design",slug:"output-tracking-control-for-fuzzy-systems-via-static-output-feedback-design",totalDownloads:2319,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"2229",slug:"fuzzy-controllers-recent-advances-in-theory-and-applications",title:"Fuzzy Controllers",fullTitle:"Fuzzy Controllers - Recent Advances in Theory and Applications"},signatures:"Meriem Nachidi and Ahmed El Hajjaji",authors:[{id:"25659",title:"Prof.",name:"Ahmed",middleName:null,surname:"El Hajjaji",slug:"ahmed-el-hajjaji",fullName:"Ahmed El Hajjaji"},{id:"141360",title:"Dr.",name:"Meriem",middleName:null,surname:"Nachidi",slug:"meriem-nachidi",fullName:"Meriem Nachidi"}]},{id:"51207",title:"Human Movement Control",slug:"human-movement-control",totalDownloads:2125,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Control theory is used to design automatic systems, which are able to maintain a desired behaviour despite of the disturbances. It is present in different machines we use every day; in fact, technical systems in our homes and all the industries are hard to imagine today without these concepts. Moreover, the same theories can be used for modelling life processes as a collection of inputs, outputs, plants and control loops. Feedback is one of the main concepts behind control; in particular, several examples of physiological control mechanisms for regulating life aspects can be found in the human anatomy, for example, blood pressure, cholesterol levels, body movements, the equilibrium, etc. Those processes can be damaged by the aging effects, diseases, accidents or when the mechanism has been broken and cannot be recovered naturally; consequently, it will be required external assistance. A relative new field in control theory is related with developing technology for helping with physiological and medicals problems. However, in comparison with machines, those physiological processes are highly nonlinear, with delays and slow responses. Another problem is when human becomes the operators using their capacities of decision making to close the control loop, as they are prone to errors and mistakes. For those reasons, the biomedical system needs to be carefully designed and several aspects have to be considered. This chapter gives a small review of some internal and external control processes within the human body and discusses how to interact with them for designing biomedical devices. Under this design scheme, a practical application of a smart electric wheelchair for assisting persons with strong disabilities is presented. These assistive robotic systems are in close contact with the user, and thus, it is determinant to have a user-friendly relation between the human and the interface. Therefore, intuitive interfaces were included in the design and an intelligent navigation assistant to guarantee a collision-free path.",book:{id:"5238",slug:"automation-and-control-trends",title:"Automation and Control Trends",fullTitle:"Automation and Control Trends"},signatures:"David Balderas and Mario Rojas",authors:[{id:"183076",title:"M.Sc.",name:"David",middleName:null,surname:"Balderas Silva",slug:"david-balderas-silva",fullName:"David Balderas Silva"},{id:"184877",title:"MSc.",name:"Mario",middleName:null,surname:"Rojas",slug:"mario-rojas",fullName:"Mario Rojas"}]},{id:"51070",title:"Fuzzy PD Controller in NAO System's Platform",slug:"fuzzy-pd-controller-in-nao-system-s-platform",totalDownloads:1588,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Humanoid robotic platforms rarely achieve the desire trajectory because of the deviation generated during the robot walking. This problem is due to different circumstances such as robot manufacturing, wear and tear of mechanic parts, or variations of floor flatness. Currently, one of the humanoid robots on the market is the robotic platform developed by Aldebaran Robotics called NAO robot, and it is used for different purposes where the robot needs to navigate into controlled spaces. NAO presents the issue of deviation during walking; therefore, a Fuzzy PD Controller is developed and implemented for this platform to reduce the orientation error and to ensure reliability during navigation. Inertial sensors are used to get the orientation reference and for feedback of the closed-loop control. Consequently, a robust control was implemented and tested in different conditions of floor and velocity during the robot’s navigation such as robot races and maze resolution. Experimental results show that fuzzy controller achieves significant improvements in the trajectories of NAO.",book:{id:"5238",slug:"automation-and-control-trends",title:"Automation and Control Trends",fullTitle:"Automation and Control Trends"},signatures:"Edgar Omar López‐Caudana and César Daniel González Gutiérrez",authors:[{id:"26464",title:"Dr.",name:"Edgar",middleName:"Omar",surname:"Lopez-Caudana",slug:"edgar-lopez-caudana",fullName:"Edgar Lopez-Caudana"},{id:"185936",title:"Mr.",name:"César Daniel",middleName:null,surname:"González Gutiérrez",slug:"cesar-daniel-gonzalez-gutierrez",fullName:"César Daniel González Gutiérrez"}]},{id:"51186",title:"Aircraft Landing Control Using the H-inf Control and the Dynamic Inversion Technique",slug:"aircraft-landing-control-using-the-h-inf-control-and-the-dynamic-inversion-technique",totalDownloads:1624,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The chapter presents the automatic control of aircraft during landing, taking into account the sensor errors and the wind shears. Both planes—longitudinal and lateral-directional—are treated; the new obtained automatic landing system (ALS) will consists of two subsystems—the first one controls aircraft motion in longitudinal plane, while the second one is for the control of aircraft motion in lateral-directional plane. These two systems can be treated separately, but in the same time, these can be put together to control all the parameters which interfere in the dynamics of aircraft landing. The two new ALSs are designed by using the H-inf control, the dynamic inversion, optimal observers, and reference models. To validate the new obtained ALS, one uses the dynamics associated to the landing of a Boeing 747, software implements the theoretical results and analyzes the accuracy of the results and the precision standards' achievement with respect to the requirements of the Federal Aviation Administration (FAA).",book:{id:"5238",slug:"automation-and-control-trends",title:"Automation and Control Trends",fullTitle:"Automation and Control Trends"},signatures:"Romulus Lungu and Mihai Lungu",authors:[{id:"181904",title:"Prof.",name:"Romulus",middleName:null,surname:"Lungu",slug:"romulus-lungu",fullName:"Romulus Lungu"}]},{id:"51936",title:"Models for the Reliability Analysis of Digital Instrumentation and Control Systems for Nuclear Power Plants",slug:"models-for-the-reliability-analysis-of-digital-instrumentation-and-control-systems-for-nuclear-power",totalDownloads:1805,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"The objective of this chapter is to discuss two approaches for reliability analysis of digital instrumentation and control systems in nuclear power plants taking into account the regulatory side. Dynamic Flowgraph Methodology (DFM) and Markov/Cell-to-Cell Mapping Technique (CCMT) are discussed and case studies developed are presented. These case studies involve simplified control systems for a steam generator and a pressurizer of a Pressurized Water Reactor (PWR) plant for the purpose of evaluating each method. Advantages and limitations of each approach are addressed. For the DFM approach, three concerns in the literature are addressed: modeling of the system itself, incorporation of the methodology results into existing Probabilistic Safety Assessments (PSA), and identification of software failures. The Markov/CCMT, which has been used in dynamic probabilistic safety assessments, is approached by means of a simplified digitally controlled water volume control system. The Markov/CCMT methodology results in detailed data of the system reliability behavior in relation to time. 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She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}}]}},subseries:{item:{id:"1",type:"subseries",title:"Oral Health",keywords:"Oral health, Dental care, Diagnosis, Diagnostic imaging, Early diagnosis, Oral cancer, Conservative treatment, Epidemiology, Comprehensive dental care, Complementary therapies, Holistic health",scope:"
\r\n This 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.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11397,editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",slug:"sandra-marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",biography:"Dr. Sandra A. Marinho is an Associate Professor and Brazilian researcher at the State University of Paraíba (Universidade Estadual da Paraíba- UEPB), Campus VIII, located in Araruna, state of Paraíba since 2011. She holds a degree in Dentistry from the Federal University of Alfenas (UNIFAL), while her specialization and professional improvement in Stomatology took place at Hospital Heliopolis (São Paulo, SP). 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). 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