\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"7639",leadTitle:null,fullTitle:"Bioinformatics Tools for Detection and Clinical Interpretation of Genomic Variations",title:"Bioinformatics Tools for Detection and Clinical Interpretation of Genomic Variations",subtitle:null,reviewType:"peer-reviewed",abstract:"Genomic variations and phenotypic diversity are closely linked and form the underlying mechanism for development of many human diseases. This book addresses the methods of detection, analysis, and interpretation of genomic variations in clinically relevant scenarios. If your research or clinical practice involves handling of genomic sequencing data, this book is for you. Topics covered include: methods for identifying genetic diversity, the workflow for analyzing whole exome and whole genome sequencing data, local ancestry deconvolution models, the value of molecular patterns and pattern biomarkers in cancer diagnosis and prognosis, and genotyping and profiling resistance-associated variants of hepatitis C. If your research or clinical practice involves handling of genomic sequencing data, this book is for you.",isbn:"978-1-78923-800-6",printIsbn:"978-1-78923-799-3",pdfIsbn:"978-1-83881-844-9",doi:"10.5772/intechopen.77443",price:100,priceEur:109,priceUsd:129,slug:"bioinformatics-tools-for-detection-and-clinical-interpretation-of-genomic-variations",numberOfPages:100,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"94f9f01b510ca80812f0eee467f9428b",bookSignature:"Ali Samadikuchaksaraei and Morteza Seifi",publishedDate:"September 4th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7639.jpg",numberOfDownloads:5483,numberOfWosCitations:11,numberOfCrossrefCitations:8,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:11,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:30,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 3rd 2018",dateEndSecondStepPublish:"November 5th 2018",dateEndThirdStepPublish:"January 4th 2019",dateEndFourthStepPublish:"March 25th 2019",dateEndFifthStepPublish:"May 24th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"187501",title:"Prof.",name:"Ali",middleName:null,surname:"Samadikuchaksaraei",slug:"ali-samadikuchaksaraei",fullName:"Ali Samadikuchaksaraei",profilePictureURL:"https://mts.intechopen.com/storage/users/187501/images/system/187501.jpeg",biography:"Professor Samadikuchaksaraei has received his MD degree from Iran University of Medical Sciences in 1998 and his Ph.D. degree from Imperial College London in 2005. His expertise is mainly focused on regenerative niche engineering for skeletal, integumentary and respiratory systems using stem cells and biomimetic materials. His publications, including book chapters, editorials, abstracts and original articles are published in collaboration with more than 300 scientists from more than 60 institutes in 10 different countries around the world. Some of his research outputs have been patented for commercial purposes. Prof. Samadikuchaksaraei serves on the editorial boards of several journals and regularly reviews for many high-profile publishers. Additionally, he reviews for granting bodies and patent and intellectual properties state organizations.",institutionString:"Iran University of Medical Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Iran University of Medical Sciences",institutionURL:null,country:{name:"Iran"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"144349",title:"Ph.D.",name:"Morteza",middleName:null,surname:"Seifi",slug:"morteza-seifi",fullName:"Morteza Seifi",profilePictureURL:"https://mts.intechopen.com/storage/users/144349/images/system/144349.jpg",biography:"Dr. Seifi has received his Ph.D. degree in Medical Genetics from the University of Alberta in 2017. Currently, he is doing his postdoctoral research fellow at the University of Alberta. His expertise is mainly focused on identification, characterization and interpretation of sequence variants in patients with genetics disorders. He has published numerous papers, several book chapters and books and presented his research at many national and international conferences. Dr. Seifi has received many prestigious awards including Izaak Walton Killam Memorial Scholarship, one of Canada\\'s largest and most prestigious endowments for scholarly activities. He has been invited to serve as judge in different symposiums and he is highly active in the peer-reviewing community and perform reviews for acclaimed journals.",institutionString:"University of Alberta",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Alberta",institutionURL:null,country:{name:"Canada"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"685",title:"Bioinformatics",slug:"engineering-biomedical-engineering-bioinformatics"}],chapters:[{id:"64947",title:"The Bioinformatics Tools for Discovery of Genetic Diversity by Means of Elastic Net and Hurst Exponent",doi:"10.5772/intechopen.82755",slug:"the-bioinformatics-tools-for-discovery-of-genetic-diversity-by-means-of-elastic-net-and-hurst-expone",totalDownloads:945,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The genome era allowed us to evaluate different aspects on genetic variation, with a precise manner followed by a valuable tip to guide the improvement of knowledge and direct to upgrade to human life. In order to scrutinize these treasured resources, some bioinformatics tools permit us a deep exploration of these data. Among them, we show the importance of the discrete non-decimated wavelet transform (NDWT). The wavelets have a better ability to capture hidden components of biological data and an efficient link between biological systems and the mathematical objects used to describe them. The decomposition of signals/sequences at different levels of resolution allows obtaining distinct characteristics in each level. The analysis using technique of wavelets has been growing increasingly in the study of genomes. One of the great advantages associated to this method corresponds to the computational gain, that is, the analyses are processed almost in real time. The applicability is in several areas of science, such as physics, mathematics, engineering, and genetics, among others. In this context, we believe that using R software and applied NDWT coupled with elastic net domains and Hurst exponent will be of valuable guideline to researchers of genetics in the investigation of the genetic variability.",signatures:"Leila Maria Ferreira, Thelma Sáfadi, Tesfahun Alemu Setotaw and Juliano Lino Ferreira",downloadPdfUrl:"/chapter/pdf-download/64947",previewPdfUrl:"/chapter/pdf-preview/64947",authors:[null],corrections:null},{id:"67673",title:"Bioinformatics Workflows for Genomic Variant Discovery, Interpretation and Prioritization",doi:"10.5772/intechopen.85524",slug:"bioinformatics-workflows-for-genomic-variant-discovery-interpretation-and-prioritization",totalDownloads:2009,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Next-generation sequencing (NGS) techniques allow high-throughput detection of a vast amount of variations in a cost-efficient manner. However, there still are inconsistencies and debates about how to process and analyse this ‘big data’. To accurately extract clinically relevant information from genomics data, choosing appropriate tools, knowing how to best utilize them and interpreting the results correctly is crucial. This chapter reviews state-of-the-art bioinformatics approaches in clinically relevant genomic variant detection. Best practices of reads-to-variant discovery workflows for germline and somatic short genomic variants are presented along with the most commonly utilized tools for each step. Additionally, methods for detecting structural variations are overviewed. Finally, approaches and current guidelines for clinical interpretation of genomic variants are discussed. As emphasized in this chapter, data processing and variant discovery steps are relatively well-understood. The differences in prioritization algorithms on the other hand can be perplexing, thus creating a bottleneck during interpretation. This review aims to shed light on the pros and cons of these differences to help experts give more informed decisions.",signatures:"Osman Ugur Sezerman, Ege Ulgen, Nogayhan Seymen and Ilknur Melis Durasi",downloadPdfUrl:"/chapter/pdf-download/67673",previewPdfUrl:"/chapter/pdf-preview/67673",authors:[{id:"283538",title:"Prof.",name:"Osman Ugur",surname:"Sezerman",slug:"osman-ugur-sezerman",fullName:"Osman Ugur Sezerman"}],corrections:null},{id:"64954",title:"Orienting Future Trends in Local Ancestry Deconvolution Models to Optimally Decipher Admixed Individual Genome Variations",doi:"10.5772/intechopen.82764",slug:"orienting-future-trends-in-local-ancestry-deconvolution-models-to-optimally-decipher-admixed-individ",totalDownloads:825,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Rapid advances in sequencing and genotyping technologies have significantly contributed to shaping the area of medical and population genetics. Several thousand genomes are completed with millions of variants identified in the human deoxyribonucleic acid (DNA) sequences. These genomic variations highly influence changes in phenotypic manifestations and physiological functions of different individuals or population groups. Of particular importance are variations introduced by admixture event, contributing significantly to a remarkable phenotypic variability with medical and/or evolutionary implications. In this case, knowledge of local ancestry estimates and date of admixture is of utmost importance for a better understanding of genomic variation patterns throughout modern human evolution and adaptive processes. In this chapter, we survey existing local ancestry deconvolution and dating admixture event models to identify possible gaps that still need to be filled and orient future trends in designing more effective models, which account for current challenges and produce more accurate and biological relevant estimates.",signatures:"Gaston K. Mazandu, Ephifania Geza, Milaine Seuneu and Emile R. Chimusa",downloadPdfUrl:"/chapter/pdf-download/64954",previewPdfUrl:"/chapter/pdf-preview/64954",authors:[null],corrections:null},{id:"65454",title:"Recognition of Multiomics-Based Molecule-Pattern Biomarker for Precise Prediction, Diagnosis, and Prognostic Assessment in Cancer",doi:"10.5772/intechopen.84221",slug:"recognition-of-multiomics-based-molecule-pattern-biomarker-for-precise-prediction-diagnosis-and-prog",totalDownloads:990,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Cancer is a complex whole-body chronic disease, is involved in multiple causes, multiple processes, and multiple consequences, which are associated with a series of molecular alterations in the different levels of genome, transcriptome, proteome, metabolome, and radiome, with between-molecule mutual interactions. Those molecule-panels are the important resources to recognize the reliable molecular pattern biomarkers for precise prediction, diagnosis, and prognostic assessment in cancer. Pattern recognition is an effective methodology to identify those molecule-panels. The rapid development of computation biology, systems biology, and multiomics is driving the development of pattern recognition to discover reliable molecular pattern biomarkers for cancer treatment. This book chapter addresses the concept of pattern recognition and pattern biomarkers, status of multiomics-based molecular patterns, and future perspective in prediction, diagnosis, and prognostic assessment of a cancer.",signatures:"Xanquan Zhan, Tian Zhou, Tingting Cheng and Miaolong Lu",downloadPdfUrl:"/chapter/pdf-download/65454",previewPdfUrl:"/chapter/pdf-preview/65454",authors:[null],corrections:null},{id:"65981",title:"HCV Genotyping with Concurrent Profiling of Resistance-Associated Variants by NGS Analysis",doi:"10.5772/intechopen.84577",slug:"hcv-genotyping-with-concurrent-profiling-of-resistance-associated-variants-by-ngs-analysis",totalDownloads:714,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Determination of viral characteristics including genotype (GT), subtype (ST) and resistance-associated variants (RAVs) profile is important in assigning direct-acting antivirals regimes in HCV patients. To help achieve the best clinical management of HCV patients, a routine diagnostic laboratory should aim at reporting accurate viral GT/ST and RAVs using a reliable diagnostic platform of choice. A laboratory study was conducted to evaluate performance characteristics of a new commercial next-generation sequencing (NGS)-based HCV genotyping assay in comparison to another widely used commercial line probe assay for HCV genotyping. Information on RAVs from deeply sequenced NS3, NS5A and NS5B regions in samples classified as HCV 1a and 1b was harnessed from the fully automated software. Perfect (100%) concordance at HCV genotype level was achieved in GT2 (N = 13), GT3 (N = 55) and GT5 (N = 7). NGS refined the ST assignment in GTs 1, 4 and 6, and resolved previously indeterminate GTs reported by line probe assay. NGS was found to have consistent intra- and inter-run reproducibility in terms of genotyping, subtyping and RAVs identification. Detection of infections with multiple HCV GTs or STs is feasible by NGS. Deep sequencing allows sensitive identification of RAVs in the GT 1a and 1b NS3, NS5A and NS5B regions, but the list of target RAVs is not exhaustive.",signatures:"Kok-Siong Poon, Julian Wei-Tze Tang and Evelyn Siew- Chuan Koay",downloadPdfUrl:"/chapter/pdf-download/65981",previewPdfUrl:"/chapter/pdf-preview/65981",authors:[null],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5450",title:"Polymerase Chain Reaction for Biomedical Applications",subtitle:null,isOpenForSubmission:!1,hash:"fcc7a13834f2748241be560e9c512a76",slug:"polymerase-chain-reaction-for-biomedical-applications",bookSignature:"Ali Samadikuchaksaraei",coverURL:"https://cdn.intechopen.com/books/images_new/5450.jpg",editedByType:"Edited by",editors:[{id:"187501",title:"Prof.",name:"Ali",surname:"Samadikuchaksaraei",slug:"ali-samadikuchaksaraei",fullName:"Ali Samadikuchaksaraei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3703",title:"New Developments in Biomedical Engineering",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"new-developments-in-biomedical-engineering",bookSignature:"Domenico Campolo",coverURL:"https://cdn.intechopen.com/books/images_new/3703.jpg",editedByType:"Edited by",editors:[{id:"1909",title:"Dr.",name:"Domenico",surname:"Campolo",slug:"domenico-campolo",fullName:"Domenico Campolo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3222",title:"State of the Art in Biosensors",subtitle:"General Aspects",isOpenForSubmission:!1,hash:"0057daafc7f0654587e99f5fc3f03a34",slug:"state-of-the-art-in-biosensors-general-aspects",bookSignature:"Toonika Rinken",coverURL:"https://cdn.intechopen.com/books/images_new/3222.jpg",editedByType:"Edited by",editors:[{id:"24687",title:"Dr.",name:"Toonika",surname:"Rinken",slug:"toonika-rinken",fullName:"Toonika Rinken"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"506",title:"Advanced Biomedical Engineering",subtitle:null,isOpenForSubmission:!1,hash:"8ae90cb19bbf5c0a612d7cf490464f8d",slug:"advanced-biomedical-engineering",bookSignature:"Gaetano D. 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\r\n\tToday, scientists describe the Universe mainly in terms of two theories: (1) Einstein's general theory of relativity (GTR), which describes the force of gravity and the large-scale structure of the Universe, and (2) quantum mechanics (QM), which describes the physics of the very small. However, as emphasized by Stephen Hawking and others, these two theories are known to be inconsistent with each other, so one needs to accommodate the gravitational force within the domain of QM by developing a quantum theory of gravity that will apply to both the large and small scales of the Universe. In a recent book entitled "The God Equation: The Quest for a Theory of Everything, Michio Kaku discusses the history and the nature of such a theory, which made significant progress during the 20th century through the development of the Standard Model (SM) of particle physics that represented the best understanding of the subatomic world at that time. Unfortunately, the SM makes no mention of the gravitational force. However, by removing several dubious assumptions made during the development of the SM, an alternative model, the Generation Model (GM), was developed from 2002-to 2019. The GM proposes that the gravitational force is not a fundamental force, as believed for centuries, but is a universal attractive, very weak residual interaction of the strong nuclear force, acting between the three massive particles, the proton, the neutron, and the electron, which are the constituents of a body of ordinary matter: this residual force provides a quantum theory of gravity. The main aim of this book is to discuss both the flaws of the SM and the GTR and also the considerable successes of the GM.
",isbn:"978-1-83768-018-4",printIsbn:"978-1-83768-017-7",pdfIsbn:"978-1-83768-019-1",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"085d4f6e00016fdad598675f825d6775",bookSignature:"Prof. Brian Albert Robson",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11861.jpg",keywords:"Standard Model, Twelve Elementary Particles, Higgs Boson Research, Universal Weak Force, CP-Violating Research, Big Bang Theory, Dark Matter, Dark Energy, Modified Gravity, Massless Elementary Particles, Quarks in Hadrons, Mixed Parity States",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 10th 2022",dateEndSecondStepPublish:"June 7th 2022",dateEndThirdStepPublish:"August 6th 2022",dateEndFourthStepPublish:"October 25th 2022",dateEndFifthStepPublish:"December 24th 2022",remainingDaysToSecondStep:"17 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"A pioneering researcher in theoretical nuclear physics and the scattering of polarized particles, recognized by Marquis Who’s Who Top Scientists for achievements and leadership in education and research. 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Currently he is an Honorary Professor in the Research School of Physics, The Australian National University, Canberra. During his academic career, he served for four years as Officer-in-Charge of the Australian National University’s first computer, for nine years as Head of the Department of Theoretical Physics, and for two years as Associate Director of the Research School of Physics and Engineering. 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The first technical shift is an outgrowth of the concept of
Technology shifts with SDN, integrated microwave photonic (IMWP) and function-transformable photonic devices are generating changes in the architecture, transport and module levels in the traditional fiber-optic links and systems.
Figure 2 shows one potential MPL in the context of a bigger configuration defined by SDN—a generic analog optical link, which we will refer to as SD-MPL. It consists of (i) a reconfigurable intensity-modulated direct-detection (IM-DD) link architecture, (ii) control plane, and (iii) network controller. The reconfigurable IM-DD comprises of three modules, namely (1) tunable transmitter, (2) fiber, and (3) receiver. The transmitter module consists of a tunable CW laser source, intensity modulator, RF driver, and RF amplifier, whereas the receiver module could be made up of fiber amplifier and photodetectors for a simple case, and might include DSP module with analog-to-digital converter (ADC) for a more sophisticated/advanced case.
\nA generic software defined IM-DD-based MPLs in context of a bigger configuration defined by SDN.
Within the context of SDN, the control plane assembles, enables, and coordinates all pertinent control signals coming from and through the transmitter and receiver modules. Then, the network controller accesses the control plane through OpenFlow interface [5, 17–20] to configure the transmitter and receiver modules. For this generic architecture to function back to traditional, standalone MPLs, the network controller and control plane can be removed and the individual control signals are now transferred to the transmitter and receiver modules of the MPLs.
\nThe second technical shift is the rapid growth of the field
The third technical shift is happening at the module level with the development of optical programmable devices and components. These programmable devices and components can have the traditional features of reconfigurability, tunability, or selectability. There are growing number of reports and demonstrations of so-called
Another implementation of these devices is based on the concept of a photonic field-programmable gate array (
However, to really support the march toward future IMWP-assisted, software-defined MPLs, it is imperative that these new photonic components not only have inherent
One of the most dominant optical transport schemes in MPLs is the intensity modulated direct detection (IM-DD) because of its simplicity and low cost. IM-DD scheme is shown in the upper portion of Figure 2. In its basic form, it consists of a RF data signal, laser source (either in the form of (i) directly modulated laser or (ii) externally modulated laser, using a combination of CW laser transmitter and optical modulator), optical fibers, optical and electrical amplifiers, and photodetector.
\nFor most low-bandwidth (<1 GHz) applications, the directly modulated laser is used as a laser source for economic reason. However, for applications that require higher linearity, larger link gain and wider bandwidth (e.g., 1–60 GHz), the use of an externally modulated laser is the most viable and common approach. It offers the best approach toward achieving higher link linearity compared with directly modulated lasers since CW lasers with very low RIN noise are commercially available. Furthermore, the high output power of a laser can act “as an indirect RF power booster” for the RF input signal to provide a positive gain rather than a negative gain (or equivalent loss) [41]. This important feature adds advantage to the link using an external modulator compared with a directly modulated laser.
The quality of the overall links performance is largely measured by four important figures-of-merit [42], namely: (1) its dynamic range in terms of the spurious-free-dynamic-range (SFDR), (2) link gain (G), (3) noise figure (NF), and (4) bandwidth. The link gain (G) describes the relationship of the RF input signal power to RF output signal power of the IM-DD link, whereas the noise figure (NF) defines the signal-to-noise ratio (SNR) degradation in the link. The SFDR depicts the RF signal power range that can be accommodated by the link, taking into account the effects of noise and nonlinear distortions. It represents the highest signal to noise ratio when the intermodulation signal power is equal to the noise floor. Thus, it combines noise and linearity performance of the link. More detailed technical discussions on these figures-of-merit are found in references [14–16, 43].
\nThe nonlinearities in any part of the links (such as laser, modulator, fiber, photodetector, amplifier, etc.) translate directly to signal noise and distortion. Nonlinear performance at the fiber occurs when the optical powers of the signals are high enough; hence, this is usually mitigated by proper engineering of the optical signal powers to avoid fiber-based nonlinearity. Similarly, detector nonlinearity is mitigated by proper optical power engineering so that the optical power impinging on the photodetector is within the linear response of the photodetector. The nonlinearity of the modulator affects the distortion and dynamic range of fiber optic links. From among these factors, the distortion produced by the external optical modulators has the most negative impact on the overall performance of the link. More specifically, the inherent nonlinear transfer function of the external intensity modulator is the dominant limitation in the performance of MPLs.
\nAs mentioned earlier, the major source of distortion in IMDD links is the nonlinearity of the intensity modulator. The quest to develop high linearity external modulator with wide bandwidth at low cost has been an on-going challenge for decades.
\nBesides linearity, other key and important attributes of an external intensity modulator include, (1) low half-wave (
Lastly, any linearized modulator must also have a high tolerance to changes in the RF power level, bias drifts, optical wavelength drifts, etc. This requirement calls for modulator with adaptive capability to provide better maintenance and stable operation of the overall MPLs.
\nThus, the focus of this book chapter is two-fold. First, it provides a comprehensive overview of the different linearization approaches that have been proposed and implemented to obtain a highly linear external intensity modulator. Second, it reviews a special type of intensity modulator called interferometric modulator with phase-modulating and cavity-modulating components (IMPACC) that is not only highly linear but also adaptive. These combined features, as far as we know, are not available with any previously reported intensity modulators.
\nThis chapter of the book is organized as follows. First, we give a brief outline of the different linearization technologies used for intensity modulator in Section 2. After a broad overview, we introduce the different optical approaches in linearizing the modulators. Then, we focus on one particular subgrouping known as MZI-based linearized modulator. In Section 3, we present a special type of MZI-based linearized modulator called IMPACC. IMPACC provides both superior linearity and unique adaptive feature. Here, we discuss its basic principle, configuration, and modeling. The comparison and discussion of the original IMPACC and ring-assisted Mach-Zenhder interferometer (RAMZI) modulator are also presented. In Section 4, we provide and analyze IMPACC and RAMZI’s respective performances before giving our conclusion in Section 5.
\nIn this section, we discuss the different linear intensity modulators. Before presenting these modulators, we first discuss an important figure-of-merit called spurious free dynamic range (SFDR) which quantifies the linearity of a given link. In Section 2.1, we discuss its derivation using a 2-tone test and graphically describe its significance. In Section 2.2, we provide an overview of the different general techniques to linearize intensity modulators before focusing on one general approach called optical linearization in Section 2.3. Optical linearization has many implementation flavors depending on the particular optical structure used for the modulator. In Section 2.4, we narrow down to a subgroup known as MZI-based modulator because of its popularity and mature technology. Within this subgroup, there are different configurations that have been proposed and implemented, and we spotlight one configuration called IMPACC.
\nA 2-tone frequency test is typically used to evaluate SFDR of the link. Figure 3(a) shows a typical IM-DD based MPL consisting of a laser, external modulator RF signal amplifier, optical fiber, photodetector, and RF output amplifier. Note that when the focus of the link is to establish the performance of the external modulator, the common practice is to consider only the intrinsic MPLs. Here, the calculation of dynamic range does not contain the effects of the optical fiber, electrical amplifiers, and optical amplifier, if present.
\n(a) Typical IMDD fiber optic link with input and output RF spectrum; (b) output RF power versus input RF power, showing the important MPL RF parameters/figures of merit, (A) fundamental curve with slope of 1, (B) second-order harmonics and intermodulation terms with slope of 2, (C) third-order intermodulation terms with slope of 3, (D) fifth-order intermodulation terms, with nonlinear slope and not the same slope in the entire frequency range, typical slope at the linear portion is 5 and corresponding SFDR calculations; (c) details of inset of (b) with the definition of the 1-dB compression point, and the
In Figure 3(a), RF input signal with two closely spaced RF frequencies, f1 and f2, of equal-power levels, are simultaneously injected into a nonlinear external optical modulator. The nonlinear interaction between these two signals will create new output frequencies, as shown in the bottom portion of Figure 3(a). Thus, the detected RF output signal will contain two fundamental frequencies, (e.g., f1 and f2) together with the second-order IMD output frequencies, (e.g., f1 + f2 and f2 −f1), second-order harmonics, (e.g., 2f1 and 2f2), and third-order IMD outputs (e.g., 2f1 − f2 and 2f2 − f1). Other higher order harmonics and IMD effects (e.g., fourth, fifth, etc.) can also be present, but their effects are generally small and can be filtered out. The second-order SFDR is only important for systems whose bandwidth is more than one octave because the second-order intermodulation products will fall outside the passband of a suboctave system. However, the most important and often most difficult to filter out are the third-order effects which occur very close to the fundamental frequencies within the system bandwidth of interest as shown in Figure 3(a).
\nInstead of giving the mathematical derivation of SFDR and other relevant parameters or merits, we present a graphical treatment in the discussion of SFDR [16]. For detailed mathematical derivation, we direct readers to relevant references [14–16]. Figure 3(b) depicts the output RF signal power versus the RF input power of the different frequency signals generated by the nonlinear interaction within the nonlinear external modulator. This single plot also demonstrates the relationships of the different parameters which we summarize below:
We should note here that
for a system limited by third-order IMD, where OIP3 is the output power at the third-order intercept point and B is the system bandwidth (with units Hz). It is simply two-thirds the difference between the largest distortion-less signal that can be input into the system and the smallest detectable signal in the system. The lower end of this range (the minimum discernable signal) is the sum of the output noise floor (PONF) and the system bandwidth, B. The measurement bandwidth is assumed to be 1 Hz. In this case, the units of SFDR are dB/Hz2/3. However, in the case of more linear systems that are limited by fifth-order IMD, SFDR is mathematically defined as [45]:
where OIP5 is the output power at the fifth-order intercept point. And, the units of SFDR for a system limited by fifth-order IMD are dB/Hz4/5. These respective SFDRs for the third-order and fifth-order are labeled as SFDR3 and SFDR5, respectively in Figure 3(b).
Note that in some new modulator designs, the fifth-order IMD curves are not always straight lines with a constant slope, but have a slight deviation from a straight line just above the noise floor. This is clearly seen in Figure 3(b), in the circled region just below the output system noise level (
Figure 4 summarizes the three general approaches used to linearize a generic external intensity modulator based on the physical mechanism used, namely: (1) electrical, (2) optical, and (3) digital (post detection). The electrical and digital linearization approaches can further be subdivided into smaller categories (as in the case of optical linearization) but we will not review this in much detail here, however more detailed information can be found in [13, 21–22, 41, 46–55].
\nGeneral classification of the different linearity approaches proposed/implemented in fiber-optics links.
Briefly speaking, the electrical linearization approach employs different techniques [46–49] such as: (i) RF predistortion, (ii) RF Feed-forward, (iii) combined RF Feed-forward and predistortion, and (iv) others. These techniques generate circuits with either (a) inverse function (ArcSin) of the modulator to predistort the RF signal before it is injected into the modulator, or (b) split a portion of the RF signal, amplify, reverse its sign, and add it to delayed original RF signal. The overall goal is to cancel or eliminate the original distorted components in the RF signal. These techniques are generally simple and inexpensive but they are limited by the frequency bandwidth of the electrical circuits [51, 53].
\nOn the other hand, a digital linearization approach is based on the application of digital signal processing, DSP [50, 52, 54] techniques to post-detected output signal. The digital approach is very promising because of its flexibility and future growth of DSP. However, its practical usefulness will depend on the progress and development in analog-to-digital converter (ADC) and digital-to-analog converter (DAC) technologies. Unfortunately, ADC is limited by the sampling rate of <10 G/sample at this time [55]. Although there are ADC/DAC technology with >10 G/sample rates, they are usually for instrument purposes [55] and not for field deployment.
\nIn contrast to electrical and digital linearization approaches, optical linearization is free from circuit frequency modulation limitation and does not utilize ADC/DAC technologies. For these reasons, we focus on the optical linearization approach in this chapter.
\nAs shown in Figure 4, the optical linearization approach can be subdivided further into 5 subgroupings, depending on the key optical structure of the modulator namely; (1) electroabsorption (EA) modulator [56–58], (2) directional coupler (DC) modulator [59–62], (3) all-optical-based approach [63–65], (4) ring resonator modulator [66–72], and (5) Mach-Zenhder interferometer (MZI)-based modulator [73–109]. These different modulators have been implemented and produced different varying degrees of linearity performance. From among these general configurations, the MZI-based modulator is the most well understood, most developed and popular optical structure in the technical community. Hence, we concentrate on the optical linearization approach with a focus on MZI-based linearized modulator.
\nTechnically speaking, the MZI-based modulator is the most well-studied type of modulator. A typical nonlinearized MZI modulator has a SFDR value of around 90–112 dB-Hz2/3. In the last decade, a wide range of linearization approaches has been proposed and implemented to improve the standard MZI modulator to have 120–130 dB-Hz2/3 SFDR range using different configurations [74–76, 78–79, 81–84]. Recently, the goal is to push the SFDR further toward >130 dB-Hz4/5. Nevertheless, most of them include complex designs and low modulation bandwidth.
\nFigure 5 shows these different types of MZI-based linearized electro-optic modulators, which can be divided into four groups depending on the actual implementations. The first group can be called dual-signal MZI-based modulator design [74–75, 83–84]. It comprises of one modulator but with two optical signals injected into the device, as depicted in Figure 5(a). The two input signal amplitudes and phases must be properly matched with predetermined values of the RF amplitude phase signal. These two injected optical signals could be implemented using (i) two polarizations [74–75], (ii) two wavelengths [84], or (iii) bidirectional signals [83]. The major advantage of this family of modulators is the relative simplicity and low cost. Its disadvantages are design inflexibility, nonoptimum performance, and tight tolerance requirements.
\nDifferent types of linear optical modulators based on MZI together with their respective implementation configurations for (a) dual-signal MZI modulator, (b) cascaded modulator, (c) RAMZI, and (d) IMPACC.
The second group can be referred to as cascaded modulator design which consists of two or more standard MZI modulators connected in series [76, 78–79, 80–82] or in parallel [100, 109] arrangements as illustrated in Figure 5(b). It is a generalization of the principle used in the first group. Its major drawbacks are the tight manufacturing tolerance requirements, higher optical loss, higher cost, due to use of multiple modulators, and complicated compensation arrangement.
\nThe third group is generally designated as RAMZI modulators [87–88, 97–99], which has received increased interest in recent years. Some implementations are shown in Figure 5(c). The RAMZI uses ring resonator(s) (RRs) instead of the standard phase modulator (PM) which is coupled in the arm(s) of the MZI. This design gives higher SFDR performance but often at higher manufacturing complexity, limited RF bandwidth range, and stricter transmission coefficient control requirement.
\nThe fourth and last group of optically linearized MZI-based modulators was introduced by our group [89, 93–94, 96, 101–105, 107–108]. This modulator design is a family of modulators which we referred to as
This section discusses the basic principle, configuration, and modeling of IMPACC. In Section 3.1, we present an overview of IMPACC configuration. For both educational as well as clarity purposes, we identify the different elements of IMPACC and discuss them separately in Section 3.2. Lastly, we bring all these elements together to come out with IMPACC modulator. While this section gives the basic principle of IMPACC, Section 4 presents its performance.
\nThe configuration of our modulator, known as IMPACC, is shown in Figure 6. IMPACC comprises of a MZI configuration, in which one of its arms (e.g., lower) has an active microring resonator (MRR) modulator, whereas the other arm (upper) has an active phase modulator (PM). It uses the standard PM as the phase modulating component and the MRR as the cavity modulating component within a MZI structure [89, 93–94, 96, 101–108]. The exact positions of the PM and MRR relative to one another offer some variations of the implementation, as shown in Figure 5(d).
\nBasic configuration of IMPACC.
Interestingly, the IMPACC configuration can be seen as a generalization of both MZI modulator and RAMZI. First, the normal combination of MZI structure and active PM in one of the arm of MZI leads to a typical
Another important aspect of IMPACC is that the RF power signal is split between the MRR and PM by the RF power splitter (PS) with a power split ratio of
The input and output optical splitters (OS and OC) in the MZI configurations are generally assumed to have a (50:50) split so that the optical signal is divided equally into two portions. However, in this chapter of the book, we generalize this condition by taking OS and OC to have arbitrary optical power split ratios namely,
The details of the design of IMPACC have been previously described [77, 89, 93–94, 101–108]. Structurally speaking, IMPACC comprises of four important building blocks namely; (1) Mach Zehnder interferometer (MZI), (2) phase modulator (PM), (3) microring resonator (MRR) modulator, and (4) RF power splitter. In order to appreciate its rich properties, we will first briefly discuss the fundamentals of each of the four important constituents namely; (i) PM, (ii) MZM, (iii) RR, and (iv) RAMZI, before they are combined and operated under certain conditions to create IMPACC.
\nThe basic principle of phase modulators is based on the Pockels or linear electro-optic effect [73]. Depending on the material used, the specific axes orientations and the relative alignment of the incoming polarization to the index ellipsoid of the material used, the net effect is the refractive index modulation based on the external applied field. There are two typical configurations, the longitudinal electro-optic modulation and the transverse electro-optic modulation. In the first case, the electric field of the modulating field is parallel to the direction of the optical beam propagation (except near the edges of the electrodes). In the second case, the electric field of the modulating field is perpendicular to the direction of the optical beam propagation. This second case offers refractive index changes induced by the external electric field
Referring to Figure 7, an incident beam propagating along the y-direction, with polarization along the
(a) Bulk electro-optic phase modulator, (b) photonic integrated waveguide electro-optic phase modulator in perspective view, (c) waveguide electro-optic phase modulator in cross-section view.
where
If the applied voltage
where
We should note here that the phase modulator in a photonic integrated waveguide circuit is slightly different as it has to be modified to accommodate a substrate structure and the electrodes. A typical, but not the only, configuration is shown in Figure 7(b) and (c). The optical waveguide is placed at the center of the gap between the two electrodes. In the optical waveguide, the direction of the field of the applied electric field is parallel to the substrate surface along the
A typical external modulator is usually in the form of an integrated optical modulator, which includes a waveguide MZI structure that is fabricated on a slab of lithium niobate (LiNbO3). To ensure that light is channeled through the waveguide, the area is typically doped with impurities in order to increase the index of refraction.
\nFigure 8 shows a typical MZI modulator configuration where the incident light is split by a Y-branch optical splitrer (OS) into the two arms of the interferometer structure. The light traversing the first arm is modulated by a RF signal. As described in the previous section, the applied electric signal induces a change in the index of refraction of the first waveguide and hence the optical signal experiences a phase shift as it propagates through the waveguide. The magnitude of the phase delay is proportional to the applied voltage and is given by [14]:
\n(a) Integrated electro-optic modulation using waveguide Mach-Zehnder Interferometer (MZI) structure, and (b) typical transfer function of a MZI.
where
where
The basic formulation for the physics of microring resonators (MRR) has been extensively discussed [85–86, 90]. We follow this analysis, in which an MRR has a total circumference length equal to
Microring Resonator (MRR) with one bus waveguide, (a) top view showing the field amplitudes at the input and output of the coupling region, (b) perspective view of the MRR with RF electrode.
In Figure 9(a), the electric fields
where
The output electric field E2, after
Here,
After
Repeating this circulation around the MRR
And finally, after infinite roundtrips, we have got the output electric field
Thus, its corresponding normalized transmission transfer function
Accordingly, the corresponding phase response,
Eqs. (14) and (16) will be handy in the analysis of the new modulator that we discuss in Section 4.
\n(A).Passive (steady-state) operation
\nThe relationship between the magnitude of the bus waveguide-to-MRR transmission coupling coefficient (
(a)The three different operating coupling conditions of MRR under critical-coupling (CC) at
(B). Dynamic operation
\nIf a voltage
where θ0 =
The parameter
For a sinusoidal voltage,
where
For a traveling wave electrode, the modulation index is given by [91–92]:
\nWhere
Figure 11(a) illustrates a RAMZI configuration where MRR is coupled to a MZI in one of its arms. We assumed that the OS and OC of the MZI have balanced (50:50) power split ratios. Then, the transfer function of RAMZI is given as [66–67, 91–92, 98]:
\n(a)Schematic of RAMZI, and (b) typical transfer function of a RAMZI under steady state condition in comparison with standard MZI.
where
On the other hand, under dynamic state (DS) where a modulating sinusoidal RF voltage
where
for a lumped electrode case. The dynamic performance of RAMZI will be shown in Section 4 together with IMPACC performance side-by-side for clear comparison.
\nAs described briefly in Section 3.1, IMPACC is a generalization of standard MZI modulator and RAMZI. Figure 12(a) shows the IMPACC configuration (a) together with its linearized transfer function (b) under its steady-state condition. Here, we assume that both OS and OC have 50:50 optical power split ratios, although later we will relax this restriction and consider arbitrary optical power split ratios namely,
(a) IMPACC configuration, and (b) its transfer function in comparison with standard MZI.
Structurally speaking, IMPACC is very much like the RAMZI configuration except for two big differences. First, the passive path-difference,
The dynamic transfer function of IMPACC,
where
\nand
\nThe parameters
Unlike RAMZI, IMPACC has an external control of either the RF power split ratio or the RF bias. As we will show in the next section, while both of these modulator designs can result in high SFDR performance, IMPACC has an additional and unique property—an adaptive, inherent compensation capability that can be used to maintain its high SFDR under three nonideal parameter conditions namely: (1) increasing MRR waveguide loss factor, (2) unfavorable MRR coupling operating conditions, and (3) unbalanced input power split ratios of either the optical splitter, OS or optical combiner, OC. This adaptive property provides an additional level of design flexibility and can greatly simplify the overall operation of high-performing modulator.
\nThis section provides details of the linearity performance of IMPACC in terms of SFDR, and compares it with RAMZI and standard MZI modulators. Unlike RAMZI and MZI modulators, IMPACC modulator has two different operational modes, namely: (i) the typical basic mode, and (ii) the unique adaptive mode. As far as we know, IMPACC is the only intensity modulator that has an adaptive mode. In Section 4.1, we focus on its basic operating mode, whereas in Section 4.2 we discuss the adaptive mode.
\nIn the basic mode, IMPACC operates under fixed, predetermined parameter conditions aimed to optimize its performance. This mode of operation is typical in all intensity modulators. Here, we investigate the effects of the different parameter variations (from these optimum conditions) on IMPACC’s SFDR performance, as well as its bandwidth capability, to assess its performance limits. These parameters include (i) MRR loss factor
Any MRR waveguide has an intrinsic loss, (expressed as loss factor,
(a) Effect of MRR waveguide loss, α on the SFDRs of IMPACC and RAMZI for ωm = 1Hz (
Figure 13(b) summarizes the full effect of MRR loss factor
The SFDR performance of any MRR-based devices, including IMPACC and RAMZI, depends highly on the relative ratio between the MRR coupling coefficient strength (
Here, we selected the three regions with the following parameters; (i) OC condition (
Briefly speaking, the SFDR performance of both IMPACC and RAMZI under OC condition is shown in Figure 14(a). IMPACC has superior linearity with SFDR =130 dB which is far better than RAMZI (e.g., 110 dB). This superior SFDR value is maintained (e.g., 129.7 dB) under CC condition as shown in Figure 14(b). Lastly, the SFDR performance of both IMPACC and RAMZI under UC condition is also shown in Figure 14(c). Under UC condition, both IMPACC and RAMZI are no better than the typical nonlinearized MZI modulator having SFDR value in the range of 110–113 dB. However, we can state that IMPACC’s SFDR value (e.g., 113 dB) is still 3 dB higher when compared with RAMZI (e.g., 110 dB). Thus, the takeaway from Figure 14 is that the huge SFDR advantage of IMPACC to RAMZI exists only when MRR is operated either in OC or CC condition.
\nSFDR performance at (a) over-coupling, (b) critical-coupling and (c) under-coupling condition for 23 GHz modulation frequency (analysis assumes a resolution BW of 1 Hz).
This section studies the effect on nonideal, unbalanced split ratios of the optical splitter (OS) or optical combiner (OC) on the SFDR performance of IMPACC for three different MRR operating conditions (OC, UC, CC) [110]. To simplify the analysis, we limit our study to unbalanced OS by maintaining OC to have 50:50 power split ratio. Note that we use the same parameters as found in Section 4.1.2 with
Figure 15(a) shows the effect of the unbalanced power split ratio (e.g., 55:45) of OS on SFDR performance of IMPACC. The SFDR value drops by 6 dB from 130 dB-Hz under balanced condition to 124 dB-Hz under unbalanced case. Figure 15(b) depicts the SFDR performance for various split ratios. It is plotted as a function of the offset from the ideal optical splitter balanced condition (0 deviation corresponds to an ideal power split ratio of 50:50) to a very unbalanced condition (e.g., 0.20 corresponds to power split ratio of 70:30 and −0.20 corresponds to power split ratio of 30:70). One conclusion from Figure 15(b) is that in order to maintain a SFDR value of above 124 dB-Hz, we need to ensure that the OS power split ratio deviation should be no greater than ± 0.08 or no more than 58:42 or 42:58 power split ratio. Note that the results of Figure 15(b) were obtained without changing any external IMPACC parameters (e.g., RF power split ratio-
(a) SFDR degradation due to particular unbalanced optical power splitter (55:45) when MRR is operated under over-coupling condition, (b) SFDR performance for different unbalanced optical power split ratios.
Figure 16 shows IMPACC’s SFDR performance under (a) CC and (b) UC conditions for balanced (i.e., 50:50) and unbalanced (e.g., 55:45) cases. We see that the SFDR value of the OC condition degrades by 11 dB from balanced case of 129 dB-Hz to 118 dB-Hz for unbalanced case. Compared with the OC case (Figure 15a) where the SFDR drops only by 6 dB, the CC condition implies higher sensitivity to OS split ratio deviation. On the other hand, Figure 16(b) illustrates that OS split ratio deviation has no effect in the balanced or unbalanced cases for UC condition. However, IMPACC has only low SFDR value of 113dB-Hz.
\nSFDR of IMPACC at over-coupling condition (a), and under-coupling condition (b) for both unbalanced and balanced scenarios (modulation frequency 23 GHz,
We know that the modulation bandwidth of all ring resonator based modulators, such as RAMZI and IMPACC is typically limited by the MRR’s free-spectral range (FSR) [91, 102, 104–105]. Here, we describe the SFDR-vs-modulation bandwidth capability of both IMPACC and RAMZI, and assess their respective performance limits. We evaluate the SFDR-vs-modulation bandwidth under lossless case (A), and under the three MRR operating conditions (B).
\nHere, we assume that the loss factor
First, Figure 17(a) shows the SFDR-vs-Modulation frequency of IMPACC (blue line), RAMZI (red line), and MZI modulator (green line) for modulation frequencies up to 75 GHz. IMPACC has an increasingly higher SFDR, (e.g., 3.7 dB to 13.7 dB) compared with RAMZI and standard MZI modulators for these increasing resonant frequencies. It is important to note that the resonance enhancement in IMPACC is accomplished without resorting to a smaller ring size. Smaller ring size not only makes the fabrication more challenging, but would also introduce larger resonator waveguide losses.
\n(a) Frequency response for the IMPACC, RAMZI, and MZI, (b) resonant region around a central modulation frequency of 23.3 GHz, (c) resonant region around a central modulation frequency of 70 GHz, (d) non-resonance region around 58 GHz. (analysis assumes a 1 Hz resolution bandwidth).
Next, we identify two frequency regions of operation: (i) the resonance region at around ~23 GHz (shown in Figure 17(b) and ~70GHz (shown in Figure 17(c)), and (ii) the non-resonance region at around 56 GHz (shown in Figure 17(d)) [105]. The resonance region is defined as the region where the SFDR is greater than that obtained from an ideal MZI, which has a relative flat response as a function of frequency. These resonant regions occur at multiples of the FSR of the modulator (e.g., 23.3 GHz, 69.9 GHz).
\nAs shown in Figure 17(a), IMPACC provides an increasingly higher SFDR, (e.g., 3.7 dB to 13.7 dB) compared with RAMZI and MZI at these resonant frequency regions. Figures 17(b) and (c) depict the respective IMPACC’s SFDR performance when the central RF modulation frequencies are set to 23 GHz and 69.9 GHz, respectively. We note that the modulation linewidth around the central frequency 23 GHz is wider compared with case of central frequency of 69.9 GHz. On the other hand, in the non-resonance region, (defined as the region between the resonance regions), the SFDR is typically less than that obtained from the ideal MZI as shown in Figure 17(d). However, the IMPACC still shows an improved SFDR performance by 0.5 to 2.0 dB compared to RAMZI.
\nFigure 18 depicts the SFDR performance of both IMPACC and RAMZI under over-coupled (OC), critical-coupled (CC), and under-coupled (UC) conditions. Figure 18(a) shows the OC IMPACC (
(a) SFDR comparison of IMPACC and RAMZI at (a) over-coupled condition, (b) critical-coupling condition, and (c) under-coupling condition for modulation frequency 23 GHz,
The case of CC IMPACC is shown in Figure 18(b). IMPACC also outperforms RAMZI within or in the resonant peak regions. Outside the resonant regions, both IMPACC and RAMZI have nearly the same performance. Lastly, Figure 18(c) shows IMPACC performance versus RAMZI in the case of UC condition at the same resonance region as above (e.g., modulation frequency ~23 GHz). In regions close to the resonance peak, the IMPACC still outperforms the ideal over-coupled RAMZI, but now the maximum difference is much smaller (e.g., ~4 dB). We note that in all these situations, we did not optimize the performance of IMPACC by changing its external parameters (e.g.,
IMPACC’s adaptive operating mode is all about using dynamically the two built-in, adjustable, and externally controllable two parameters to maintain IMPACC’s 130 dB SFDR performance under unfavorable parameter conditions such as: (i) intrinsic RR loss, (ii) parameter variation of
The ability to adjust the control parameters
(a) IMPACC compensates for MRR intrinsic losses to obtain SFDR values above 130 dB, (b) RF power split ratio adjustments required to achieve high SFDR (e.g., >130 dB) performance under MRR with exhibited insertion losses.
The result of this adaptive mode is to maintain the SFDR value to higher than 130 dB by dynamically changing the required
In this section, we highlight IMPACC’s ability to compensate the negative effect due to unbalanced optical splitter performance [110, 113]. Figure 20(a) shows the SFDR performance of OC IMPACC (
SFDR comparison of (a) over-coupled and (b) critical-coupling condition for RAMZI and IMPACC for both unbalanced and balanced scenarios (modulation frequency 23 GHz, ξPM = 1.3893π,
This is emphasized in Figure 20(a) where the original drop of 6 dB in the SFDR performance, when the optical splitter is nonideal (55:45), can be compensated to return to SFDR value equal to 129 dB by adjusting the external parameters,
In UC condition, the inherent compensation capability of IMPACC is severely limited and cannot increase the SFDR of IMPACC for the unbalanced case. Adjusting the external parameters,
As discussed earlier in Section 4.1.3, all ring resonator based modulators (e.g., RAMZI and IMPACC) are limited by the FSR of the ring resonator [88, 91–92, 94,102,104–108]. This is graphically represented by the narrow Lorentzian shape of its SDFR profile as depicted in Figures 17 and 18. This limitation is troublesome, especially for wideband RF link applications. Fortunately, the IMPACC has significant advantage compared with RAMZI and other linear modulators that relaxes this built-in RF modulation bandwidth limitation due to MRR.
\nIMPACC can broaden the SFDR profile at its peak value by dynamically adjusting both
Changing the power split ratio
In summary, electro-optic modulators are critical part of optical communications. They will continue to play an important role in fiber optic links. However, an essential requirement is that they have linear response with a high dynamic range of input RF powers of multiple tones. We have shown that IMPACC can operate with highly linear response with peak SFDR value of 132 dB.
\nAnother important requirement in the link design is the inherent versatility of the device or link to compensate for unexpected changes or unavoidable parameter variations due to environmental temperature change, device aging, and fabrication errors. In this regard, IMPACC has a unique place among previously reported linear intensity modulators since it is the only linear modulator design, as far as we know, that has an inherent compensation capability. We demonstrated this inherent feature by compensating various nonideal and often detrimental effects in the modulator from RR waveguide loss and unbalanced optical inputs to various coupling conditions that could lower manufacturing tolerance and degrade linearity performance if not mitigated. The ability to maintain high SFDR (e.g., >130 dB) under these conditions makes IMPACC a viable candidate for many high-bandwidth RF FO-link applications, and well positioned as ideal linear intensity modulator for software-defined MPLs
\nNM would like to thank partial support from the European Committee under program FP7-MC-CIG 333829.
\nMammalian central nervous system (CNS) consists of brain and spinal cord. The neuronal network extends from the brain to all over the body and various neurotransmitters help transmit the message to target cells in different tissues. The part of the nervous system located in our gut is called the enteric nervous system (ENS). In all animals, gut brain axis is a lesser known nervous system so far. Our gut or “second brain” (ENS) chemically connects with the brain through neurons, secreted chemicals like hormones and neurotransmitters that send messages to the brain. The enteric nervous system’s network of neurons and neurotransmitters extends along the entire digestive tract – it starts from the esophagus to the stomach and intestines, and down to the anus. The “gut microbiome” comprises of microorganisms living in the gut (bacteria, viruses, and fungi) that can affect the chemical messages that pass between the gut and the brain. Microorganisms residing in the gut help regulate the body’s immune response. Since, the brain and the gastrointestinal (GI) system are intimately connected, therefore, they play key roles in certain diseases and to maintain our overall health to regulate cognitive and digestive behavior. The bidirectional communication between the brain and digestive system hence, are opening up avenues to think about diseases considering this angle.
Gut has recently become a subject of research in medical sciences wherein subjects with depressive symptoms, Parkinson’s and Alzheimer’s disease, autism, amyotrophic lateral sclerosis, multiple sclerosis, pain, anxiety and other neurodegenerative conditions are beginning to be looked to see what is going on in the gut. Effects of conditions like ulcers, constipation, and other GI problems have been a focus of research on aspects of brain functioning. The enteric microbiota impacts the gut brain axis (GBA), interacts locally with the intestinal cells and ENS as well as with the CNS through neuroendocrine and metabolic pathways. These studies suggest that GBA plays a vital role in maintaining mental health and can affect the feeding behavior when nutrient detection or absorption does not function properly as in case of metabolic conditions.
To ensure stability in the internal environment of body and drive adaptive changes, control mechanisms are key to animal’s survival. Recently GI has been recognized as a major source of signals modulating feeding behaviors, food intake, metabolism, insulin secretion and energy balance. Through its interaction with microbiota, it can shape our physiology and behavior in complex and sometimes unexpected ways. A growing scientific community has exploited the genetic amenability of
Easy genetic manipulation and effortless genetic tools make flies an insect of choice to study inter organ neuronal signaling including gut-brain axis neuronal connectivity. To understand human metabolic diseases and how a GI play a key role there is a recent focus of research. Some progressive studies also draw a link between neurodegenerative disorders and gut microbiota of humans and other insects.
Fruit flies have a simple and similar to humans- gut system (Figure 1). In mammals including humans, the esophagus (
Comparison between human and
The adult
Fly gut anatomy. (A) the
The fly midgut has been segmented into the anterior, middle and the posterior midgut (Figures 1,2A and B). It has been further subdivided morphologically and molecularly into 10–14 regions (Figure 2B) [11, 12, 13]. Midgut regionalization has been seen in the muscles, trachea and neurons that surround it [12, 13, 14, 15]. Physical properties (
The Malpighian tubules release at the junction between the midgut and hindgut (Figures 1,2A and B). The water/ion exchange occurs in the hindgut which consist of pylorus (a second valve-like structure), ileum, and rectum [7, 8]. The muscles that surround the epithelium in flies are striated, as opposed to the smooth muscles found in mammalian intestines [18]. An outer layer of longitudinal muscles found surrounding the midgut. Circular muscles are found to be present throughout the fly tract. Physiology of the intestine is maintained and regulated by autonomic innervation and by hormones. The tracheal system forms a branched structure surrounding the gut during development [15] and may influence epithelial regeneration in the adult. Owning to similarity of flies and human gut, we will be discussing further how gut of the flies is handled and controlled to understand about neural circuitry drawing it closer to the brain and diseases related to intestinal illnesses.
Both humans and fly intestines share similar tissue, anatomy and physiological function [19, 20]. Their gut are of endothelial origin in nature [21, 22] and comprise of an epithelial monolayer of columnar or cuboidal ECs. A series of sequential depressions called the crypts of Lieberkühn, along the small and large intestine, and protruding villi along the internal surface of the small intestine in mammalian intestinal epithelium maximize its surface area [23]. Extensive folding has not been reported in the
In both flies and mammals, the epithelial monolayer is associated on its basal side on an extracellular collagenous matrix (known as basement membrane) [29]. A checkerboard of innervated and trachea-oxygenated longitudinal and circular muscles tissue underneath the basement membrane in flies drive the peristaltic movements [30] (Figure 2C). Mammalian intestine has a similar organization of intestinal external musculature in the outer layers where musculature is also innervated and oxygenated by a plexus of vasculature [31, 32]. Layers including, the submucosa, (a dense layer of connective tissue containing nerves and lymphatic and blood vessels); muscularis mucosae (an additional muscle layer); and the lamina propria underling the intestinal epithelium and contains connective tissue, lymph nodes (Peyer’s patches), immune cells (leukocytes, and dendritic and mast cells), vessels and myofibroblasts [33], fill the space between the outer musculature and the basement membrane in mammals.
About 65% of human-disease causing genes are shared as a functional homolog in fruit flies. This shows conservation of genes and function at an evolutionary level. Fundamental processes such as digestion is also conserved from flies to humans.
The lineage of fly posterior midgut with only one type of mature absorptive cell and one main type of secretory cell is very simple. Although asymmetric ISC divisions in the fly midgut produce transient cells (EBs), these cells do not undergo further cell division and remain close to the ISCs before maturation. Fly midgut ISCs are situated basally and are broadly dispersed in the intestinal epithelium. The cellular composition and regeneration in
Like the regional specialization of digestive functions, the expression of digestive enzymes has also been found to confined to specific segments of the digestive tract in flies [12, 46, 47]. In addition to its roles in nutrient extraction and utilization, the digestive tract responds to the food and bacteria in its lumen. Digestion takes place in fly midgut [48] which can be further modulated by various factors like temperature, redox potential, pH, and intestinal transit [8, 48]. It has been shown that the expression and activity of digestive enzymes are tightly regulated in many insects like enzymes involved in the breakdown of sugars in flies are enriched in anterior (R1/R3) portions of the adult midgut and Peptidase genes express more posteriorly [47].
The enzymatic activity of the intestine is a key factor determining availability of certain nutrients. A substantial reduction of intestinal digestive enzyme activities (trypsin, chymotrypsin, aminopeptidase, and acetate esterase) has been reported in flies lacking EE cells [49]. Though not extensively investigated in
Changes in the expression of p38 kinase or the Atf3 and Foxo transcription factors cause accumulation of neutral lipid in ECs [58, 84]. It has been shown that neutral lipid increase following depletion of the EE hormone Tk [85], or in sterile female flies after mating [86]. It has been suggested that activation of intestinal lipogenesis is key to survival in diet-restricted flies. Indeed, nutrient scarcity induces expression of the sugar sensor transcription factor
Many animals generate localized regions of low pH inside the intestinal lumen to facilitate protein breakdown, absorption of minerals and metals, and limit the survival of ingested microbes. While mammalian digestion takes place in acidic conditions, insect digestion occurs at neutral or basic pH including
The contribution of five ion transporters enriched in the acidic region have been studied [88]. These include: the potassium/chloride symporter Kazachoc (Kcc), a member the Slc12 family of electroneutral cation-chloride transporters (express in intestine) [91, 92]; the Slowpoke pore-forming subunit of a calcium-activated K+ channel (express in neurons, muscles, tracheal cells, and two types of midgut ECs in the copper and iron cell regions) [93]; the ligand-gated chloride channel pHCL-2 which, in addition to regulating fluid secretion in malpighian tubules (express in the copper cell, iron, and large flat cell regions of the midgut) [94, 95]; the carbonic anhydrase CAH1; and the bicarbonate/chloride exchanger CG8177, belonging to the Slc4a1–3 subfamily of anion exchangers (express in a specific midgut pattern similar to that of pHCl-2) [96]. Collectively, these findings suggest that the transport of H+, Cl−, K+, and HCO3− contributes to acid generation in the
Flies extract water from their diet to maintain hydration and ionic balance. This compensates for substantial water loss resulting from metabolic and physiological processes. Although malpighian tubules are important for this process, but intestine also contributes. Water absorption from the food occurs in the insect midgut and in rectal pads of rectum [8]. The rectal pads are also the crucial site for reabsorption of ions. Ions and water can cross the intestinal epithelium through or between cells and their transport play an important role in the maintenance of ion gradients that sustain active transport in the intestinal epithelium. The scanning ion-selective electrode technique (SIET) provides a way to probe intestinal gradients for ions such as K+, Na+, H+, or Cl− [24, 97]. K+ and Na+ absorption occur largely in the large flat cell and posterior regions of the midgut and, also in the anterior hindgut in the case of Na+ [97]. The two
Metal ions such as copper, iron and zinc are essential micronutrients required for the correct folding and activity of a broad range of enzymes. The contribution of the intestine to metal homeostasis has not been extensively investigated but midgut regions, the Cu cell and Fe regions, are the most proposed sites of metal ion absorption. The Cu cell region turns bright luminescent orange upon Cu ingestion due to the fixation of copper by metallothionein [101, 102], and appears to be an important site of accumulation of ingested radioactively labeled Cu [101, 103]. The Fe cell region in R4a stains by Prussian blue and also accumulates exogenously administered radioactive Fe [101, 104]. Many studies have confirmed the roles for the Cu/Fe regions by exploring the molecular machinery involved in the intestinal uptake, intracellular trafficking, and efflux of metal ions.
Nutrient extraction and utilization may get affected by the passage of food along the alimentary canal and by its subsequent excretion. Transport of food to travel the entire length of the digestive tract takes less than 1 hour [105] in flies. As suggested, the amount of food retained in the crop is much larger in starved flies then refed flies than in flies fed
The ENS in humans, equivalent to GBA in flies is a part of the peripheral nervous system (PNS) that governs the running of the neurons which influence the GI. It is exploited nowadays in flies to understand more about how the two organs affect one another and lead to decisions regarding appetite, feeding mechanisms, taste preference and how to deal with hunger and satiety. How taste receptors detect different nutrients in the gut remains to be explored.
In humans, G-protein coupled receptors (GPCR) are involved in detection of five common tastes- sweet, salty, bitter, sour and umami. T1R family of taste receptors determine sweet and umami flavor. T2R family includes the bitter receptors [110]. Sweet taste receptors (T1R family) are found in intestinal tract as well as EE cells [111]. T1R1, T1R2, T1R3 and α-gustducin are expressed in the stomach, intestine and colon of humans and mice [112]. Cells of duodenal villi show co-localization of T1R1, T1R3 and α-gustuducin. Mammalian Gustducin protein is involved in bitter and sweet taste signaling and detection [113, 114]. α-subunit of gustducin is expressed in gastric cells and may play a role in nutrient detection [115, 116, 117] in rats and mice. Present in the mucosal lining of mammals and taste cells of the epithelium suggesting its possible role in taste uncovering on exposure to luminal contents [118]. Expression of T2R receptors in mouse GI tract including mT2R119 and mT2R108 has been looked into. mT2R119 expression is found in gastric and intestinal tissues, tongue and liver [115] like mT2R134 [118]. mT2R108, mT2R138 are present in the fundus, antrum, duodenum and tongue (not in liver) [119].
It has been found that sweet taste receptors stimulated in rat intestine influence and increase glucose absorption [120] through GLUT (glucose transporter) [121]. Presence of sugar in the diet galvanizes ECs into action to release hormones which in turn activate SGLT (Na+ / glucose cotransporter) [122, 123]. Similar results are shown in sheep where sugar receptor / sensor present on the luminal membrane stimulates SGLT1 via cAMP and G-protein dependent pathway [124]. Equine T1R2 (homologous to cows and pigs) is expressed on the luminal membrane of EE cells in the small intestine. In response to increased sugars, T1R2 along with T1R3, stimulates SGLT1 and enhances the ability of gut to absorb more glucose [125]. Analysis of in vitro line of ECs suggest that T1R2 and T1R3 detect sweet taste and exposure to sucralose increases release of hormones such as GIP (Gastric Inhibitory Polypeptide) and GLP (Glucagon like peptide) which further activate glucose activation and metabolism. An inhibitor of these receptors inhibits glucose metabolism suggesting these receptors present in the gut alter feeding mechanisms and post-ingestion decisions [120, 121].
Gustatory system in
Nutrient signaling and sensing are fundamental processes that animals including humans and flies undergo [131]. Proper coordination and communication between gut and brain is necessary to regulate metabolic homeostasis and physiology in all animals. In this regard, many research groups have shown the role of enteric neurons and endocrine signals as important mediators of these processes. The way the enteric nervous system communicates to the brain via neural circuits is a multifaceted question and poorly explored. In mammals such as humans, alterations in neuropeptides and brain – gut hormone levels can derail people otherwise on the path to a healthy life. These changes can also lead to diseases such as neurodegenerative diseases, metabolic syndrome and diabetes [132].
Gluconeogenesis is a biochemical pathway by which animals make sugars from non-carbohydrate precursors and sources [133]. It is used to regulate homeostasis and a stable internal state in post – fed state [134]. Studies in rats showed that stimulation of intestinal gluconeogenesis (IGN) sends a signal from sodium – glucose co- transporters present at the intestinal mucosa to the brain, initiating a neural gut – brain axis [135, 136, 137]. Diets rich in protein [138, 139, 140] and fiber [141] promote IGN stressing on the importance of nutrient sensing for initiating several gut – brain axis [137]. It has been found that μ – opoid receptors (MOR) regulate IGN. These receptors (present in the nerves in the portal vein wall) react to neuropeptides to stimulate a gut – brain neural circuit that affects IGN, hunger and satiety mechanisms [141]. Further analysis of MOR deficient mice shows the role of MORs in regulating food intake, referred as “reward” system [142, 143]. Analyses of MOR-knockouts (MOR-KO) demonstrate how they play a role in managing satiety effects of alimentary proteins, through a neural gut-brain circuit [140].
Vagus nerve (VN; pneumogastric nerve) is the longest cranial nerve [144] in humans which runs from the medulla oblongata in brain to colon in GI [145]. It innervates other structures as well such as larynx, pharynx, heart and lungs thus affects digestive, cardiovascular and respiratory system – all at one [146]. Vagal efferent send down signals from the brain to gut, which accounts for about 10% – 20% of all the nerve fibers. Remaining 80% is accounted for by the vagal afferents carrying information from the gut to the brain [147]. Vagal sensory neurons in the GI keep an eye on stomach volume and luminal contents through different neural circuits [148]. VN contains and branches into several sensory neurons (~2300 in mouse) that further innervate and render support and supply to other internal organs. A variety of sensory neurons, one side facing the brainstem and the terminal one facing the organ such as GI [149] have been revealed. Free terminals of vagal afferents are rooted within lamina propria of intestinal villi [148]. Some mammalian models like in cat and rat, it has been shown how these sensory neurons detect different nutrients in diets with the help of unambiguous and explicit fibers [150, 151, 152]. Vagal afferent endings in the intestine express several mechanosensitive as well as chemical receptors [153]. Glucagon- like peptide 1 (GLP1) is a gut hormone receptor that intercedes the nutrient sensing mechanism via VN [154]. GLP1R (GLP1 receptor) is present in many cells [155]. Agonists for GLP1R show how it affects brain further proving its presence in both, gut and brain [156]. Another receptor of vagal afferents, GPR65 near the intestinal villi, plays a role in nutrient detection drawing attention to how these sensory neurons are a part of the gut – brain axis [157, 158]. It detects serotonin and impact gut motility [147]. Such receptors detect several hormones present in the gut, like choleocystokinin (CKK), ghrelin and leptin which play a role in the regulation of hunger and satiety [159, 160, 161]. Because of its role in gut motility and mobility, VN and its afferent neurons present in the gut play a role in Intestinal Bowel Syndrome (IBS) [162] and new treatment plans around the same are being looked at in rat [162] and mice [158] models.
To take the findings in vagal nerves forward, nerves allowing communication of cNST (caudal nucleus of the solitary tract) with gut were focused on. Information about sugar detection to cNST via gut – brain axis is a topic of research nowadays. In live mice, it is noticed that glucose detection by cNST is robust and VN transaction silences that activation [163]. Nodose ganglion of vagus nerve when silenced prevents the sugar preference of cNST [163] suggesting the presence of a physical gut – brain axis. It has been shown that inactivation of sugar-activated cSNT prevents the mice to choose sugar from water or an artificial sweetener [163]. This study specifically calls attention to how organisms have paths for detecting nutrient signals, sensing them in the diet and also have circuitries to carry forward the signals and communicate with the rest of the body, purposely the brain.
With the help of several markers and reporter genes, it is found that
In the anterior portion of adult and larval midgut, serotonin positive neurites and various neuropeptides including Akh, Dh44, Myosuppressin, and possibly Allatostatin C and FMRFamide (or an FMRFamide-like peptide such as the NPY-like neuropeptide short neuropeptide F [sNPF]) [131, 168, 172, 180, 181, 182] have been described suggesting chemical diversity of enteric innervation. Four serotonergic neurons are found to innervate the enteric nervous system in fly larva. These neurons project from the antennal nerve (AN) near the SEZ and extend throughout the ENs [14]. These projections end at the anterior region of the midgut and are primarily around the proventriculus region and the foregut. These innervations are considered structurally analogous to the mammalian VN because of similar projections from the brain to the different structures of the foregut. It is yet to be seen if there are functional similarities as well [172].
Pigment- dispersing factor (Pdf), Ion transport peptide, and Proctolin positive neurites have been reported in the larval and adult hindgut [169, 183, 184, 185, 186]. All three innervated regions receive insulinergic innervation from the CNS; the
Innervation of adult
Functional studies of insect innervation have primarily focused on the control of peristalsis and peptide hormone secretion so far. Studies of peristaltic regulation in flies have primarily concerned the effects of neuropeptides (Allatostatins, Myosuppressin, or Drosulfakinins) on
Recently epithelial roles for gut-innervating neurons e.g. role in the control of fluid balance have been revealed by a semi-automated analysis of defecation behavior in adult flies, providing quantitative readouts for food intake, fluid/ion balance, and intestinal transit [14, 193]. The HGN1 neurons (2–5 CNS neurons located in the posterior segments of the abdominal ganglion) innervate the hindgut and the rectum (Figure 3), with a subset of their neurites projecting through the visceral muscles to reach the underlying epithelium [14]. HGN1 neuronal silencing experiments resulted in increased defecation rate. These neurons are shown to be required for the post-mating changes in intestinal fluid retention due to their epithelial innervation. It has been established that HGN1 neurons and the Pdf hindgut-innervating neurons have their direct action on the hindgut and anal sphincter muscles [192]. A role for gut-innervating neurons in the maintenance of epithelial turnover has also been suggested by the finding of anatomical proximity between enteric neurites in the posterior midgut and adult somatic intestinal progenitors, and the reduced ISC to EC differentiation resulting from downregulating Hedgehog (Hh) signaling (albeit pan-neuronally) [194]. The more anterior innervation of the proventriculus may also play a role in maintaining gut permeability. This is inferred from the finding that inactivation of a relatively broad subset of neurons, including a subset of anterior midgut-innervating neurons results in an abnormal proventricular structure, increased permeability of the epithelial barrier, and increased susceptibility to oral bacterial infection: all suggestive of defects in the production of peritrophic matrix [175].
In adult flies, inactivation of insulin-producing neurons results in contrasting effects on the hyperphagic response triggered by nutrient scarcity. Silencing of the insulin-producing cells of the brain PI that innervates the anterior midgut lowered this response, whereas silencing of the hindgut-innervating Ilp7 neurons increased it, and also resulted in higher circulating glucose [14, 195]. Not much is known about the importance of sparse sensory innervation of the intestine. One remarkable exception are the pharyngeal taste neurons.
Post-ingestive sensory feedback from the gut has been assumed to inhibit feeding based on work in other insects for example severing the recurrent nerve or the medial abdominal nerve, which transmit information from the gut to the brain, results in overconsumption in blowflies [199]. Work done in flies lends support to this idea; whereas severing the medial abdominal nerve did not disturb food consumption, severing the recurrent nerve elevated consumption of sucrose but not water or bitter tasting solutions [200]. The existence of neuronal stretch receptors on the gut that monitor the volume of ingested food is supported by both neurophysiological and anatomical data in numerous other insects [4, 80, 199, 201]. However, the existence and molecular nature of these receptors in
The gut–brain transmission systems involve both circulation-based endocrine-like and neuronal communication routes [205]. Neuropeptides (transmitters or neurosecretory) act as messenger molecules of enteric, sensory, autonomic and central neurons. Several peptide families have been found in both brain and gut. They act as neuropeptides and/or gut hormones and have significantly contributed to the understanding of gut brain interaction. Central and peripheral neurons together with EE cells in the GI tract and other endocrinologically active cells produce variety of peptides [206, 207, 208, 209, 210, 211] including hormones peptide YY (PYY) and pancreatic polypeptide (PP); neuropeptide Y (NPY), on the other hand [212]. These and other peptide families represented by glucagon-like peptide (GLP), ghrelin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), leptin, osteocalcin and insulin (the last three are extra intestinal endocrine peptides) act on specific and genetically related groups of receptors that are expressed by distinct cells in the periphery and CNS. For their functional roles, endocrine peptides and neuropeptides are relevant for the regulation of digestion, control of food intake, metabolic homeostasis, and the impact of GI signals on sensation, emotion, affect, and cognition. Disturbances of the gut microbiota–brain axis result in changes of the expression and activity of many neuropeptides and their receptors in the CNS. Neuropeptides are therefore important secondary messengers of gut microbes in cerebral neuro circuitries that mediate the alterations in brain function and behavior that take place in response to changes in the GI microbial community [212]. Together it is emerging that neuropeptide systems such as NPY, CRF, ghrelin, and brain-derived neurotrophic factor (BDNF) play a particular role in the cerebral manifestations of gut microbiota perturbations.
In rats, choleocystokinin and glutamate neuro-epithelial circuit makes the communication between the brain and intestinal lumen possible stressing on the importance of a physical gut – brain axis [213]. It has been proposed that the physical connection between vagal nodose neurons and EE cells is present in rats which leads to regulation of gastrointestinal functions [213]. Intragastric nutrient infusion and optical readings of AgRP (Agouti-related protein) neurons in live and awake mice [214] suggest AgRP neurons affect long term homesostasis and energy balance of the body and do not get altered by minute changes in nutrient levels [215]. AgRP neurons get inhibited by high levels of satiation signals such as CCK and PYY (peptide YY). Receptors for both CCK and PYY are expressed by vagal afferent neurons’ terminals that innervate GI [159] suggesting a possibility of a physical connection between the gut and brain carrying the message from one point to another [216].
Apart from using neurons, fly intestine can also communicate with other organs through systemic signals. Intestinal physiology is modulated by both extrinsic hormonal signals (emanating from endocrine glands, neuroendocrine structures, or organs such as the fat body) and by its own peptide hormones, produced by EE cells. In turn, gut-derived signals such as EE cell-derived peptide hormones can have long-range effects on other internal organs. EE cells accounts for 5–10% of midgut epithelial cells in flies compared to 0.4–0.6% in the mammalian small intestine [217, 218, 219]. Majority of them express peptide hormones, often more than one and with regional stereotypy [219, 220, 221, 222]. The developmental program of EE cells shares similarities with that of neurons, probably reflecting a common phylogenetic origin [223, 224, 225]. Consistent with this idea, all known EE peptide hormones (exception insect CCHamides) [226] are also produced by the brain. Acting through these hormones, EE cells may play “neural-like” roles in regulating intestinal physiology and conveying intestinal as well as nutritional state to other cell types or organs. These roles are particularly prominent in the midgut given the relatively sparse innervation of midgut region.
A role for EE cells on muscle peristalsis has been suggested by the finding that ablation of Diuretic hormone 31 (Dh31)-expressing EE cells or Dh31 downregulation both reduce muscle peristalsis in the larval anterior midgut, which may function as a valve to minimize mixing of acidified and non-acidified food in the acidic region of the midgut [227]. Adult EE cells produce Bursicon. Signaling through the Bursicon/DLGR2 receptor in visceral muscle, represses the production of the visceral muscle-derived mitogen Vein and, consequently, ISC proliferation. Another study found in
A high-sugar diet leads to increased midgut EE cell number and enhanced production of EE-derived Activin ligand (Activin-β not Daw) [230] suggesting systemic roles for EE-derived peptide hormones. Mirroring the activin-mediated fat-to-gut signaling involved in sucrose repression, midgut-derived Activin-β binds to the TGF-β receptor Baboon in fat cells which, in turn, leads to enhancement of Akh signaling it the fat body and consequent hyperglycemia [230]. CCHamides are insect hormones [231, 232] and their expression is promoted by nutrient availability and sites of expression include the gut EE cells, a subset of central neurons and, possibly, the fat body [226, 233, 234]. Their receptors are expressed in the nervous system including the insulin-producing neurons, and are absent from the gut [226, 234]. Although not strictly gut-derived, a new peptide hormone produced not by EE cells, but by an adjacent secretory gland may have provided the most compelling example to date of gut-to-brain communication. Indeed, Limostatin (Lst) peptide is produced by the
In animals with a vascular system, peptides secreted from EE cells can enter the bloodstream and reach tissues at a considerable distance, ranging from other cells in the digestive tract to brain centers regulating appetite [236]. Nutrient availability can also affect the number of EE cells; signaling through the nuclear hormone receptor Hr96, dietary lipids control EE differentiation during the first few days of adult life, providing another way to couple nutrient availability with tissue architecture and physiology [237]. Modulation of intestinal physiology by systemic signals has also been looked into [220, 221]. Control of epithelial turnover by insulin-like peptides or JH (juvenile hormone), and the coupling of dietary availability of sugars with EC digestive enzyme production via the fat body-derived Activin ligand Daw are some examples. The actions of the diuretic peptide Leucokinin (Lk), secreted into the circulation from CNS-derived nerves that terminate at the abdominal wall [14, 238, 239] is an another example. Downregulation of either this peptide or its receptor leads to abnormal excreta and extreme fluid retention that can rupture the abdominal wall [14]. Finally, a link between energy balance, intestinal permeability, and immunity has been suggested by the finding that sNPF is a target of the Crtc/CREB energy sensing pathway, and functions to maintain epithelial barrier integrity acting through its receptor in ECs [240]. Although the precise source of sNPF remains to be established, tissue-specific genetic and expression data points to roles in neurosecretory cells [240], consistent with roles as a neuroendocrine hormone or in gut-innervating neurons. Gut can also produce long-range signals to affect the physiology of other organs, for example by production of the signaling protein Hh by larval EC. Circulating Hh regulates developmental timing by controlling ecdysteroid production in the prothoracic gland, and is required for mobilization of fat body TAG stores during starvation [241].
Other functions of brain-gut peptides and hormones include detection and utilization of nutrients during hunger, stress or normal conditions. Diuretic hormone 44 (Dh44), a homolog of the mammalian corticotropin –releasing -hormone (CRH) activate by nutritive sugars. Disturbed activity of Dh44 neurons leads to fail to select nutritive sugars [131]. These neurons localized to PI in adult brain, counterpart of mammalian hypothalamus [242] are filled with neurosecretory cells [131]. Dh44 conveys information from Dh44 neurons to Dh44 receptor R1 neurons in the brain and R2 cells in the gut suggesting requirement for nutrient selection. Artificial activation of these neurons causes rapid PER and it has been suggested that Dh44 is necessary and sufficient for gut motility and excretion in flies [131]. Both Dh44 neurons and the gut-innervating insulin-producing neurons of the PI are innervated by Hugin-producing neurons that suppress food intake and induce locomotion, providing a possible link between food-related behaviors and intestinal physiology [243]. It is seen later that Dh44+ neurons rapidly activate during amino acid feeding and are a direct sensor of dietary amino acids [244].
Fly gut peptide Dromyosuppressin [181] expresses in the number of cells in central nervous system (CNS) in adult stage, extending into the rectum, near the anus; part of the adult gut. Their immunoreactive fibers also project into the crop and show expression of Dromyosuppressin [172] and crop abundantly expresses Dromyosuppressin receptors (Dromyosuppressin receptor I) [220]. The effects of neuropeptide on neural regulation of crop motility and contractions have been shown [245]. Serotonergic neurons have also been shown to regulate insulin producing cells (IPC) located in the PI of the adult brain of the fly [246]. DILP2, 3 and 5 express particularly in midgut [187, 220, 247] and extend their axons to proventriculus, crop and corpora cardiaca [248]. DILP2 is particularly involved in carbohydrate metabolism [249]. Decreased levels of DILP2 affects stored trehalose as well [248]. IPC knockdown flies show increased glycogen storage, high levels of circulating triglycerides and extended lifespan [248].
Mammalian neuropeptide NPY (Neuropeptide – Y- precursor) has an invertebrate homologous peptide called NPF due to characteristic C- terminal F residue [250]. NPF has been shown to co- localize within midgut cells in
Other neuropeptides include Allatostatin characterized into three kinds namely Allatostatin A/B/C [258, 259, 260]. The endocrine cells producing Allatostatin are found in the posterior midgut and is innervated by axons from thoracico-abdominal ganglion [220]. Its receptors, DAR1 and DAR2 are predominantly located in the central nervous system and gastrointestinal tract (including crop, midgut and hindgut) respectively [261, 262]. Allatostain is also present throughout midgut. Another major peptide is PDF. It is expressed in central nervous system [263] and its neurons are also found in thoracico-abdominal ganglion [184]. Axons from these neurons innervate midgut and hindgut and in the crop. These neuropeptides are closely associated to circadian rhythm [264] and locomotor activity as well.
Various studies have suggested that intestinal health has a significant impact on neurodegeneration. Specifically, dysregulation of GBA cross talk has been associated with metabolic syndrome [265, 266] and psychiatric disorders. GBA is largely mediated by CNS, ENS and intestinal microbiota. With its much simpler gut microbiota (1–30 taxa) as opposed to vertebrates intestine (1–500 taxa) [267],
Most genes and pathways that play crucial roles in metabolic diseases are conserved between flies and humans [268]. Diet-induced obesity in flies is associated with many of the pathophysiological consequences found in humans, including hyperglycemia, insulin resistance, cardiac arrhythmia and fibrosis, reduced longevity [269, 270] and nephrosis [271]. The gut is crucial for peripheral body fat storage and serves as a major site of dietary lipid absorption and absorbs other dietary macronutrients (sugars, proteins and fats). It also metabolizes both glucose and lipids into metabolic intermediates, which after loading into hemolymph get used in other tissues and organs. In flies, lipoprotein complexes containing apolipophorins carry sterols and diacylglycerols from the gut to other tissues [81]. Fly lipoproteins also contain Hh, a cholesterol-linked, gut-derived ligand that binds the transmembrane receptor Patched on fat body target cells to promote lipolysis during larval starvation [241, 272]. The human anti-obesity drug orlistat, a gastric lipase inhibitor, has been shown to reduce body fat accumulation in adult flies [56]. Supporting a crucial role for lipolysis, midgut lipid accumulation and global fat storage are reduced by the insulin signaling pathway inhibitor Foxo in enterocytes, via reducing the expression of
The gut microbiota and its metabolism plays an important role in modulation of fat storage in the fly. As seen in humans, fly gut is enriched in
Recently
In the recent past, data from the intestinal mechanisms found in flies have been shown to be active in mammals, and may therefore become relevant in the context of human pathologies including diabetes, obesity, neurodegenerative diseases, gastrointestinal cancers, or aging. Parallel findings of communication between gut and brain via neuropeptides in
Developing new techniques and behavioral assays can help us explore physiological drives: what is the gut function to maintain the overall health of the animal. It would be interesting to find out the key intestinal sensors. How the physical association between gut and brain via neural micro circuits regulate decisions regarding nutrition, hunger and satiety is under question. Better “holistic” and quantitative methods, integration of spatial and temporal information about genetic events more comprehensively are required, so that cause and effect can be uncoupled in a physiological context [306]. We anticipate and hope that fly models of intestinal pathology, in addition to uncovering newly identified genes (chemosensory and others) and basic biology mechanisms will emphasize the most conserved aspects of human intestinal biology. As a result, fly will contribute to translational research investigating drug effects, and microbial and host genetic component analyses, leading to biological findings that are broadly applicable to human health and disease.
The authors declare no conflict of interest.
This work is supported by Wellcome Trust/DBT India Alliance Fellowship (grant number IA/I/15/2/502074) awarded to PK.
ZS, SK and PK all substantially contributed to the conception and design of the work. Everybody participated in drafting and revising the work, made the figures, wrote the chapter and approved the final version for publication.
ENS | Enteric nervous system |
GI | Gastrointestinal |
GBA | Gut brain axis |
CNS | Central nervous system |
ISCs | Intestinal stem cells |
ECs | Enterocytes |
EE | Enteroendocrine |
EBs | Enteroblasts |
TA | Transient amplifying |
AMP-5′ | Adenosine monophosphate |
AMPK- 5’ | AMP activated kinase |
TAG | Triacylglyceride |
Sug | Sugarbabe |
CD36 | Cluster of differentiation 36 |
Npc1 | Niemann-Pick C1 |
SREBPs | Sterol regulatory element-binding proteins |
Akh | Adipokinetic hormone |
RNAi | RNA interference |
Kcc | Kazachoc |
SIET | Scanning ion-selective electrode technique |
Dh44 | Diuretic hormone 44 |
GPCR | G-protein coupled receptors |
PNS | Peripheral nervous system |
GLUT | Glucose transporter |
SGLT | Na+/glucose cotransporter |
GIP | Gastric inhibitory polypeptide |
GLP | Glucagon like peptide |
TK | Tachykinin |
MOR | μ – opoid receptors |
IGN | Intestinal gluconeogenesis |
MOR-KO | MOR-knockouts |
cNST | Caudal nucleus of the solitary tract |
GLP1 | Glucagon- like peptide 1 |
sNPF | Short neuropeptide F |
AN | Antennal nerve |
Ilp7 | Insulin-like peptide 7 |
VN | Vagus nerve |
IBS | Intestinal bowel syndrome |
HGN1 | Hindgut neuron1 |
Hh | Hedgehog |
Poxn | Pox-neuro |
Dh31 | Diuretic hormone 31 |
Lst | Limostatin |
Lk | Leucokinin |
JH | Juvenile hormone |
Crtc/CREB | cAMP-regulated transcriptional co-activator/ cyclic AMP-responsive element-binding protein |
SEZ | Suboesophageal zone |
CRH | Corticotropin –releasing -hormone |
PI | Pars intercerebralis |
IPC | Insulin producing cells |
DILP | Drosophila insulin- like- peptide |
5-HT1A-5 | Hydroxy tryptamine /serotonin |
AKH | Adipokinetic hormone |
PYY | Peptide YY |
AgRP | Agouti-related protein |
CCK | Choleocystokinin |
PP | Pancreatic polypeptide |
NPY | Neuropeptide Y |
Pigment- dispersing factor | |
CRF | Corticotropin-releasing factor |
BDNF | Brain-derived neurotrophic factor |
SCFAs | Short-chain fatty acid |
AMP | Anti-microbial peptide |
ROS | Reactive oxygen species |
DUOX | Dual oxidase |
IMD | Immune deficiency |
APC | Adenomatous polyposis coli gene |
CRC | Colorectal cancer |
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This approach is now an international priority that proceeds together with the inclusion of the structuring species in numerous directives.",book:{id:"5765",slug:"corals-in-a-changing-world",title:"Corals in a Changing World",fullTitle:"Corals in a Changing World"},signatures:"Michela Angiolillo and Simonepietro Canese",authors:[{id:"197032",title:"Ph.D.",name:"Michela",middleName:null,surname:"Angiolillo",slug:"michela-angiolillo",fullName:"Michela Angiolillo"},{id:"197763",title:"Dr.",name:"Simonepietro",middleName:null,surname:"Canese",slug:"simonepietro-canese",fullName:"Simonepietro Canese"}]},{id:"60698",doi:"10.5772/intechopen.74923",title:"Overview on Mediterranean Shark’s Fisheries: Impact on the Biodiversity",slug:"overview-on-mediterranean-shark-s-fisheries-impact-on-the-biodiversity",totalDownloads:1092,totalCrossrefCites:12,totalDimensionsCites:16,abstract:"Bibliographic analysis shows that the Mediterranean Sea is a hot spot for cartilaginous species biodiversity, including sharks, rays, and chimaeras; 49 sharks and 36 rays were recorded in this region. However, they are by far the most endangered group of marine fish in the Mediterranean Sea. The IUCN Red List shows clearly the vulnerability of elasmobranchs and the lack of data; 39 species (53% of 73 assessed species) are critically endangered, endangered, or vulnerable. The biological characteristics of elasmobranchs (low fecundity, late maturity, and slow growth) make them more vulnerable to fishing pressure than most teleost fish. Overfishing, the wide use of nonselective fishing practices, and habitat degradation are leading to dramatic declines of these species in the Mediterranean Sea. In general, elasmobranchs are not targeted but are caught incidentally. In many fisheries, they are, however, often landed and marketed. A decline in cartilaginous fish species landings has been observed while fishing effort has generally increased. Better understanding of the composition of incidental and targeted catches of sharks by commercial fisheries are fundamentally important for the conservation of these populations. Moreover, problems encountered by elasmobranchs in the area are highlighted, and conservation measures are suggested.",book:{id:"6266",slug:"marine-ecology-biotic-and-abiotic-interactions",title:"Marine Ecology",fullTitle:"Marine Ecology - Biotic and Abiotic Interactions"},signatures:"Mohamed Nejmeddine Bradai, Bechir Saidi and Samira Enajjar",authors:null}],mostDownloadedChaptersLast30Days:[{id:"60368",title:"Biological and Medicinal Importance of Sponge",slug:"biological-and-medicinal-importance-of-sponge",totalDownloads:2505,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Sponges are multicellular, heterotrophic parazoan organisms, characterized by the possession of unique feeding system among the animals. They are the most primitive types of animals in existence, featuring a cell-based organization where different cells have different tasks, but do not form tissues. Sponges (Porifera) are a predominantly marine phylum living from the intertidal to the abyssal (deepest ocean) zone. There are approximately 8500 described species of sponges worldwide with a prominent role in many reef coral communities. Several ecological studies reported have shown that secondary metabolites isolated from sponges often serve defensive purposes to protect them from threats such as predator attacks, biofouling, microbial infections, and overgrowth by other sessile organisms. In the recent years, interest in marine sponges has risen considerably due to presence of high number of interesting biologically active natural products. More than 5300 different natural products are known from sponges and their associated microorganisms, and every year hundreds of new substances are discovered. In addition to the unusual nucleosides, other classes of substances such as bioactive terpenes, sterols, fatty acids, alkaloids, cyclic peptides, peroxides, and amino acid derivatives (which are frequently halogenated) have been described from sponges or from their associated microorganisms. Many of these natural products from sponges have shown a wide range of pharmacological activities such as anticancer, antifungal, antiviral, anthelmintic, antiprotozoal, anti-inflammatory, immunosuppressive, neurosuppressive, and antifouling activities. This chapter covers extensive work published regarding new compounds isolated from marine sponges and biological activities associated with them.",book:{id:"6344",slug:"biological-resources-of-water",title:"Biological Resources of Water",fullTitle:"Biological Resources of Water"},signatures:"Musarat Amina and Nawal M. Al Musayeib",authors:[{id:"213049",title:"Dr.",name:"Musarat",middleName:null,surname:"Amina",slug:"musarat-amina",fullName:"Musarat Amina"},{id:"213050",title:"Dr.",name:"Nawal",middleName:null,surname:"M. Al Musayeib",slug:"nawal-m.-al-musayeib",fullName:"Nawal M. Al Musayeib"}]},{id:"59865",title:"Marine Fisheries in Nigeria: A Review",slug:"marine-fisheries-in-nigeria-a-review",totalDownloads:3852,totalCrossrefCites:8,totalDimensionsCites:10,abstract:"Fisheries production especially from marine is important for the socio-economic development of Nigerians and its contribution to the nation’s economic growth through the Gross Domestic Product (GDP). Nigeria is blessed with enough marine fisheries resources that could enhance increased fish production. Yet, fish supply from domestic production is far below the fish demand of her citizens. This chapter is therefore focused on marine fisheries in Nigeria. We adopted a desk review approach. This chapter is divided into different sections such as the Nigerian fisheries sector, marine fisheries resources in Nigeria, status of marine fisheries production in Nigeria, marine fisheries regulations, and constraints to optimal marine fisheries production in Nigeria. We concluded that the contribution of aquaculture to marine fisheries production has been low, compared to the marine capture fisheries production. Also, we noted that despite the availability of regulations, noncompliance by fisher folks has not helped to optimize marine fisheries production. We therefore recommended that the culture of marine fishes should be intensified. Marine waters should also be protected against destruction and pollution as a result of human activities. Available marine fisheries regulations should be enforced and violators of the regulations should be punished as stipulated in the regulations.",book:{id:"6266",slug:"marine-ecology-biotic-and-abiotic-interactions",title:"Marine Ecology",fullTitle:"Marine Ecology - Biotic and Abiotic Interactions"},signatures:"Olalekan Jacob Olaoye and Wahab Gbenga Ojebiyi",authors:null},{id:"57327",title:"Closed Aquaculture System: Zero Water Discharge for Shrimp and Prawn Farming in Indonesia",slug:"closed-aquaculture-system-zero-water-discharge-for-shrimp-and-prawn-farming-in-indonesia",totalDownloads:2465,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"This chapter focuses on the development and application of zero water discharge (ZWD) system, which has become an alternative solution to conventional methods of aquaculture production. With this system, it is expected to answer many issues in aquaculture cultivation, such as environmental damage, disease outbreak, and land-use change, and to create a sustainable aquaculture cultivation system. ZWD system is an improved batch system with an emphasis on microbial manipulation in rearing tank. The principle of microbial selection is based on the role of each microbial component in nutrient cycle in the rearing tank. This chapter contains in detail how methods and stages are performed in order to conduct this system, including design of construction system, cultivation of microbial components, initial conditioning of this system, and microbial manipulation. The performance of the system was tested in crustacean culture such as white shrimp and giant freshwater prawns, and it showed that the system can increase the average survival rate of 10–20%. In addition, the technical and economic feasibility of this system was evaluated to illustrate the production efficiency upon the application of this system in the industry.",book:{id:"6344",slug:"biological-resources-of-water",title:"Biological Resources of Water",fullTitle:"Biological Resources of Water"},signatures:"Gede Suantika, Magdalena Lenny Situmorang, Pingkan Aditiawati,\nDea Indriani Astuti, Fahma Fiqhiyyah Nur Azizah and Harish\nMuhammad",authors:[{id:"216920",title:"Dr.",name:"Gede",middleName:null,surname:"Suantika",slug:"gede-suantika",fullName:"Gede Suantika"},{id:"220079",title:"Dr.",name:"Magdalena Lenny",middleName:null,surname:"Situmorang",slug:"magdalena-lenny-situmorang",fullName:"Magdalena Lenny Situmorang"},{id:"220081",title:"Dr.",name:"Pingkan",middleName:null,surname:"Aditiawati",slug:"pingkan-aditiawati",fullName:"Pingkan Aditiawati"},{id:"220082",title:"Dr.",name:"Dea Indriani",middleName:null,surname:"Astuti",slug:"dea-indriani-astuti",fullName:"Dea Indriani Astuti"},{id:"220083",title:"MSc.",name:"Fahma Fiqhiyyah Nur",middleName:null,surname:"Azizah",slug:"fahma-fiqhiyyah-nur-azizah",fullName:"Fahma Fiqhiyyah Nur Azizah"}]},{id:"59973",title:"Genetic Applications in the Conservation of Neotropical Freshwater Fish",slug:"genetic-applications-in-the-conservation-of-neotropical-freshwater-fish",totalDownloads:1626,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"Neotropical fish correspond to approximately 30% of all fish species worldwide. The diversity of fish species found in Neotropical basins reflects variations in life-history strategies and exhibition of particular morphological, physiological and ecological attributes. These attributes are mainly related to different forms of feeding, life maintenance and reproduction. Today, fish populations are being threatened by anthropogenic actions that are having a visible impact on the natural state of continental aquatic ecosystems. The main causes are overfishing, non-native species introduction, reservoir-dam systems, mining, pollution and deforestation. The biology and population dynamics of the species are still unclear due to lack of research. Genetic tools can be useful resources for the conservation of Neotropical fish species in several ways. Molecular genetic markers are considered powerful tools to identify cryptic and hybrid fish and also allow the evaluation of the genetic variability and structure of populations of Neotropical ichthyofauna. Several analyses of molecular markers have been performed on Neotropical fish, including allozyme analysis, restriction fragment length polymorphisms in regions of DNA (RFLP), randomly amplified polymorphic DNA (AFLP), randomly amplified polymorphic DNA (RAPD), microsatellites, single nucleotide polymorphisms (SNPs) and mitochondrial DNA (mtDNA) markers. In order to analyse a high number of markers, next generation sequencing has allowed researchers to generate a large amount of genomic information that can be applied to the conservation of Neotropical fish.",book:{id:"6344",slug:"biological-resources-of-water",title:"Biological Resources of Water",fullTitle:"Biological Resources of Water"},signatures:"Vito Antonio Mastrochirico Filho, Milena V. Freitas, Raquel B.\nAriede, Lieschen V.G. Lira, Natália J. Mendes and Diogo T.\nHashimoto",authors:[{id:"215385",title:"Dr.",name:"Diogo",middleName:null,surname:"Hashimoto",slug:"diogo-hashimoto",fullName:"Diogo Hashimoto"},{id:"226741",title:"MSc.",name:"Vito",middleName:null,surname:"Matrochirico-Filho",slug:"vito-matrochirico-filho",fullName:"Vito Matrochirico-Filho"},{id:"226743",title:"MSc.",name:"Milena",middleName:null,surname:"Freitas",slug:"milena-freitas",fullName:"Milena Freitas"},{id:"226744",title:"MSc.",name:"Raquel",middleName:null,surname:"Ariede",slug:"raquel-ariede",fullName:"Raquel Ariede"},{id:"226745",title:"MSc.",name:"Natália",middleName:null,surname:"Mendes",slug:"natalia-mendes",fullName:"Natália Mendes"},{id:"226746",title:"MSc.",name:"Lieschen",middleName:null,surname:"Lira",slug:"lieschen-lira",fullName:"Lieschen Lira"}]},{id:"62582",title:"Mangrove Species Distribution and Composition, Adaptive Strategies and Ecosystem Services in the Niger River Delta, Nigeria",slug:"mangrove-species-distribution-and-composition-adaptive-strategies-and-ecosystem-services-in-the-nige",totalDownloads:2139,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Mangroves of the Niger River Delta grade into several plant communities from land to sea. This mangrove is a biodiversity hot spot, and one of the richest in ecosystem services in the world, but due to lack of data it is often not mentioned in many global mangrove studies. Inland areas are sandy and mostly inhabited by button wood mangroves (Conocarpus erectus) and grass species while seaward areas are mostly inhabited by red (Rhizophora racemosa), black (Laguncularia racemosa) and white (Avicennia germinans) mangroves species. Anthropogenic activities such as oil and gas exploration, deforestation, dredging, urbanization and invasive nypa palms had changed the soil type from swampy to sandy mud soil. Muddy soil supports nypa palms while sandy soil supports different grass species, core mangrove soil supports red mangroves (R. racemosa), which are the most dominant of all species, with importance value (Iv) of 52.02. The red mangroves are adapted to the swampy soils. They possess long root system (i.e. 10 m) that originates from the tree stem to the ground, to provide extra support. The red mangrove trees are economically most viable as the main source of fire wood for cooking, medicinal herbs and dyes for clothes.",book:{id:"6411",slug:"mangrove-ecosystem-ecology-and-function",title:"Mangrove Ecosystem Ecology and Function",fullTitle:"Mangrove Ecosystem Ecology and Function"},signatures:"Aroloye O. Numbere",authors:[{id:"215285",title:"Dr.",name:"Aroloye O.",middleName:null,surname:"Numbere",slug:"aroloye-o.-numbere",fullName:"Aroloye O. Numbere"}]}],onlineFirstChaptersFilter:{topicId:"659",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:249,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"13",type:"subseries",title:"Plant Physiology",keywords:"Plant Nutrition, Plant Hormone, Photosynthesis, Respiration, Plant Stress, Multi-omics, High-throughput Technology, Genome Editing",scope:"Plant Physiology explores fundamental processes in plants, and it includes subtopics such as plant nutrition, plant hormone, photosynthesis, respiration, and plant stress. In recent years, emerging technologies such as multi-omics, high-throughput technologies, and genome editing tools could assist plant physiologists in unraveling molecular mechanisms in specific critical pathways. The global picture of physiological processes in plants needs to be investigated continually to increase our knowledge, and the resulting technologies will benefit sustainable agriculture.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. 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