Histological classification of ovarian sex cord-stromal tumorsa.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"10882",leadTitle:null,fullTitle:"Smart Drug Delivery",title:"Smart Drug Delivery",subtitle:null,reviewType:"peer-reviewed",abstract:"This book brings together recent developments in the field of drug delivery. Technological advancements in the field of pharmaceutical sciences have revolutionized the patient care industry. The book serves to bridge the gap between the current research scenario and the technical knowledge provided at the pharmaceutical institutions to maximize the skills of individuals involved at any level in this domain. Chapters address topics related to the formulation and evaluation of drug delivery systems, various targeting approaches and novel tools, and design and statistical techniques employed to develop robust and effective dosage forms.",isbn:"978-1-83969-539-1",printIsbn:"978-1-83969-538-4",pdfIsbn:"978-1-83969-540-7",doi:"10.5772/intechopen.95191",price:119,priceEur:129,priceUsd:155,slug:"smart-drug-delivery",numberOfPages:208,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"70c3ce4256324b3c58db970d446ddac4",bookSignature:"Usama Ahmad, Md. Faheem Haider and Juber Akhtar",publishedDate:"July 6th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10882.jpg",numberOfDownloads:1056,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:1,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:2,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 18th 2021",dateEndSecondStepPublish:"March 18th 2021",dateEndThirdStepPublish:"May 17th 2021",dateEndFourthStepPublish:"August 5th 2021",dateEndFifthStepPublish:"October 4th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Integral University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Integral University",institutionURL:null,country:{name:"India"}}},coeditorTwo:{id:"252107",title:"Dr.",name:"Juber",middleName:null,surname:"Akhtar",slug:"juber-akhtar",fullName:"Juber Akhtar",profilePictureURL:"https://mts.intechopen.com/storage/users/252107/images/system/252107.jpg",biography:"Dr. Juber Akhtar obtained a BPharm from Jamia Hamdard University, New Delhi, in 2005, MPharm from Manipal University, Karnataka, in 2007, and Ph.D. from Integral University, Lucknow, in 2014. He is currently an associate professor at Integral University. From 2014 to 2016, Dr. Akhtar was head of the Faculty of Pharmacy, Integral University. He also served as chairman cum biological scientist for Institutional Animal Ethics Committee (IAEC) from October 2015 to May 2017. He has experience teaching abroad and was previously a professor at Buraydah College of Pharmacy and Dentistry, Kingdom of Saudi Arabia (KSA). Dr. Akhtar has more than eighty publications in reputed journals and is an editorial board member for many esteemed journals. He has supervised a dozen Ph.D. and MPharm students in research projects. Dr. Akhtar’s areas of research interest include the development of nanoparticulate drug delivery systems.",institutionString:"Integral University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Integral University",institutionURL:null,country:{name:"India"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1194",title:"Drug Delivery System",slug:"drug-delivery-system"}],chapters:[{id:"78928",title:"Drug Delivery through Liposomes",doi:"10.5772/intechopen.97727",slug:"drug-delivery-through-liposomes",totalDownloads:16,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Several efforts have been focused on targeted drug delivery systems for delivering a drug to a particular region of the body for better control of systemic as well as local action. Liposomes have proven their efficiency as a choice of carrier for targeting the drugs to the site of action. The main reason for continuous research on liposomes drug delivery is they largely attributed to the fact that they can mimic biological cells. This also means that liposomes are highly biocompatible, making them an ideal candidate for a drug delivery system. The uses found for liposomes have been wide-spread and even include drug delivery systems for cosmetics. Several reports have shown the applicability of liposomal drug delivery systems for their safe and effective administration of different classes of drugs like anti tubercular, anti cancer, antifungal, antiviral, antimicrobial, antisense, lung therapeutics, skin care, vaccines and gene therapy. Liposomes are proven to be effective in active or passive targeting. Modification of the bilayer further found to increase the circulation time, improve elasticity, Trigger sensitive release such as pH, ultrasound, heat or light with appropriate lipid compositions. The present chapter focuses on the fundamental aspects of liposomes, their structural components, preparation, characterization and applications.",signatures:"Srinivas Lankalapalli and V.S. Vinai Kumar Tenneti",downloadPdfUrl:"/chapter/pdf-download/78928",previewPdfUrl:"/chapter/pdf-preview/78928",authors:[{id:"231435",title:"Prof.",name:"Srinivas",surname:"Lankalapalli",slug:"srinivas-lankalapalli",fullName:"Srinivas Lankalapalli"},{id:"351733",title:"Dr.",name:"V.S. Vinai",surname:"Kumar Tenneti",slug:"v.s.-vinai-kumar-tenneti",fullName:"V.S. Vinai Kumar Tenneti"}],corrections:null},{id:"78379",title:"Protein and Peptide Drug Delivery",doi:"10.5772/intechopen.99608",slug:"protein-and-peptide-drug-delivery",totalDownloads:18,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Protein and peptide-based drugs have great potential applications as therapeutic agents since they have higher efficacy and lower toxicity than chemical drugs. However, difficulty with their delivery has limited their use. In particular, their oral bioavailability is very low, and the transdermal delivery faces absorption limitations. Therefore, most of the protein and peptide-based drugs are administered by the parenteral route. However, this route also has some problems, such as patient discomfort, especially for pediatric use. Extensive research has been performed over the past few decades to develop protein and peptide delivery systems that circumvent the problems mentioned above. Various strategies that have been employed during this time include nanoparticle carriers, absorption enhancers, enzyme inhibitors, mucoadhesive polymers, and chemical modification of protein or peptide structures. However, most of these strategies are focused on the delivery of proteins or peptides via the oral route since it is the most preferred route considering its high level of patient acceptance, long-term compliance, and simplicity. However, other routes of administration such as transdermal, nasal, pulmonary can also be attractive alternatives for protein and peptide delivery. This chapter will discuss the most effective approaches used to develop protein and peptide drug delivery systems.",signatures:"Nitai Charan Giri",downloadPdfUrl:"/chapter/pdf-download/78379",previewPdfUrl:"/chapter/pdf-preview/78379",authors:[{id:"356406",title:"Assistant Prof.",name:"Nitai",surname:"Charan Giri",slug:"nitai-charan-giri",fullName:"Nitai Charan Giri"}],corrections:null},{id:"78313",title:"Smart Drug-Delivery Systems in the Treatment of Rheumatoid Arthritis: Current, Future Perspectives",doi:"10.5772/intechopen.99641",slug:"smart-drug-delivery-systems-in-the-treatment-of-rheumatoid-arthritis-current-future-perspectives",totalDownloads:232,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Rheumatoid arthritis (RA) is a progressive autoimmune inflammatory disorder characterized by cellular infiltration in synovium causing joint destruction and bone erosion. The heterogeneous nature of the disease manifests in different clinical forms, hence treatment of RA still remains obscure. Treatments are limited owing to systemic toxicity by dose-escalation and lack of selectivity. To overcome these limitations, Smart drug delivery systems (SDDS) are under investigation to exploit the arthritic microenvironment either by passive targeting or active targeting to the inflamed joints via folate receptor, CD44, angiogenesis, integrins. This review comprehensively deliberates upon understanding the pathophysiology of RA and role of SDDSs, highlighting the emerging trends for RA nanotherapeutics.",signatures:"Largee Biswas, Vikas Shukla, Vijay Kumar and Anita Kamra Verma",downloadPdfUrl:"/chapter/pdf-download/78313",previewPdfUrl:"/chapter/pdf-preview/78313",authors:[{id:"351722",title:"Associate Prof.",name:"Anita",surname:"Kamra Verma",slug:"anita-kamra-verma",fullName:"Anita Kamra Verma"},{id:"419119",title:"MSc.",name:"Largee",surname:"Biswas",slug:"largee-biswas",fullName:"Largee Biswas"},{id:"419120",title:"Mr.",name:"Vikas",surname:"Shukla",slug:"vikas-shukla",fullName:"Vikas Shukla"},{id:"419121",title:"Dr.",name:"Vijay",surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar"}],corrections:null},{id:"79411",title:"Phospholipid Based Nano Drug Delivery Systems of Phytoconstituents",doi:"10.5772/intechopen.101040",slug:"phospholipid-based-nano-drug-delivery-systems-of-phytoconstituents",totalDownloads:157,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"The development of phytochemistry and phyto-pharmacology has enabled elucidation of composition and biological activities of several medicinal plant constituents. However phytoconstituents are poorly absorbed due to their low aqueous solubility, large molecular size and poor membrane permeability when taken orally. Nanotechnology based drug delivery systems can be used to improve the dissolution rate, permeability and stability of these phytoconstituents. The current chapter aims to present the extraction of phytoconstituents, their identifications, and development/utilization of phospholipid based nano drug delivery systems (PBNDDS). The content of the chapter also provides characteristic features, in-vitro, in-vivo evaluations and stability performance of PBNDDS. The results from the UHPLC and GC-MS showed different phytoconstituents in the extracted samples with quantitative value. Dynamic light scattering (DLS) data showed PBNDDS of different phytoconstituents in the range of 50–250 nm with PDI value of 0.02–0.5, which was also confirmed by the electron microscopic data. Phytoconstituents loading or entrapment for PBNDDS was in the range of 60–95%. PBNDDS exhibited better in-vitro and in-vivo performance with improved Physico-chemical stability.",signatures:"Mohammad Hossain Shariare and Mohsin Kazi",downloadPdfUrl:"/chapter/pdf-download/79411",previewPdfUrl:"/chapter/pdf-preview/79411",authors:[{id:"187082",title:"Prof.",name:"Mohsin",surname:"Kazi",slug:"mohsin-kazi",fullName:"Mohsin Kazi"},{id:"355488",title:"Associate Prof.",name:"Mohammad Hossain",surname:"Shariare",slug:"mohammad-hossain-shariare",fullName:"Mohammad Hossain Shariare"}],corrections:null},{id:"79292",title:"Aliphatic Polyester Nanoparticles for Drug Delivery Systems",doi:"10.5772/intechopen.100977",slug:"aliphatic-polyester-nanoparticles-for-drug-delivery-systems",totalDownloads:134,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Drug delivery systems using aliphatic polyester nanoparticles are usually prepared via an emulsion process. These nanoparticles can control drug release and improve pharmacokinetics. Aliphatic polyesters are linear polymers containing ester linkages, showing sensitivity to hydrolytic degradation. The byproducts then promote autocatalytic degradation. These byproducts could enter the Krebs cycle and be eliminated from the body, resulting in the high biocompatibility of these nanoparticles. The properties of these polyesters are linked to the drug release rate due to biodegradation, i.e., polymer crystallinity, glass transition temperature, polymer hydrophobicity, and molecular weight (MW), all of which relatively influence hydrolysis. Mathematical equations have been used to study the factors and mechanisms that affect drug dissolution compared to experimental release data. The equations used as models for predicting the kinetics of drug release include the zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas equations. Aliphatic polyester-based controlled drug delivery has surrounded much of the current activity in the estimation parameters of nanoparticles and stimulated additional research. Polymeric nanoparticles have potential in a wide range of applications, such as in biotechnology, vaccine systems, and the pharmaceutical industry. The main goal of this chapter is to discuss aliphatic polyester nanoparticles as drug carrier systems.",signatures:"Narumol Kreua-ongarjnukool, Nopparuj Soomherun, Saowapa Thumsing Niyomthai and Sorayouth Chumnanvej",downloadPdfUrl:"/chapter/pdf-download/79292",previewPdfUrl:"/chapter/pdf-preview/79292",authors:[{id:"418423",title:"Dr.",name:"Nopparuj",surname:"Soomherun",slug:"nopparuj-soomherun",fullName:"Nopparuj Soomherun"},{id:"419970",title:"Prof.",name:"Narumol",surname:"Kreua-ongarjnukool",slug:"narumol-kreua-ongarjnukool",fullName:"Narumol Kreua-ongarjnukool"},{id:"419971",title:"Dr.",name:"Saowapa",surname:"Thumsing Niyomthai",slug:"saowapa-thumsing-niyomthai",fullName:"Saowapa Thumsing Niyomthai"},{id:"419972",title:"Prof.",name:"Sorayouth",surname:"Chumnanvej",slug:"sorayouth-chumnanvej",fullName:"Sorayouth Chumnanvej"}],corrections:null},{id:"78619",title:"Strategies to Develop Cyclodextrin-Based Nanosponges for Smart Drug Delivery",doi:"10.5772/intechopen.100182",slug:"strategies-to-develop-cyclodextrin-based-nanosponges-for-smart-drug-delivery",totalDownloads:147,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In recent years, the development of various cyclodextrin (CD)-based nanosponges (NSs) has gained great importance in the controlled and-or targeted release of drugs due to their versatility and simple preparation. In this chapter, an introduction of different administration routes is explained. Further, different ways to obtain CD-NSs and their classification are shown with a brief explanation of the characterization of the inclusion complexes. Finally, illustrative examples in diverse processes or diseases will be reviewed and explained to demonstrate the potential of CD-NSs. Therefore, this division will serve to compile information on CD-NSs in recent years and to illustrate to readers how to generate and apply different derivatives of interest.",signatures:"Gjylije Hoti, Silvia Lucia Appleton, Alberto Rubin Pedrazzo, Claudio Cecone, Adrián Matencio, Francesco Trotta and Fabrizio Caldera",downloadPdfUrl:"/chapter/pdf-download/78619",previewPdfUrl:"/chapter/pdf-preview/78619",authors:[{id:"354544",title:"Prof.",name:"Francesco",surname:"Trotta",slug:"francesco-trotta",fullName:"Francesco Trotta"},{id:"418841",title:"Ms.",name:"Gjylije",surname:"Hoti",slug:"gjylije-hoti",fullName:"Gjylije Hoti"},{id:"418842",title:"Ms.",name:"Silvia",surname:"Lucia Appleton",slug:"silvia-lucia-appleton",fullName:"Silvia Lucia Appleton"},{id:"418844",title:"Dr.",name:"Alberto",surname:"Rubin Pedrazzo",slug:"alberto-rubin-pedrazzo",fullName:"Alberto Rubin Pedrazzo"},{id:"418845",title:"Dr.",name:"Claudio",surname:"Cecone",slug:"claudio-cecone",fullName:"Claudio Cecone"},{id:"418846",title:"Dr.",name:"Adrián",surname:"Matencio",slug:"adrian-matencio",fullName:"Adrián Matencio"},{id:"418847",title:"Dr.",name:"Fabrizio",surname:"Caldera",slug:"fabrizio-caldera",fullName:"Fabrizio Caldera"}],corrections:null},{id:"78844",title:"Targeted Nano-Drug Delivery System to Colon Cancer",doi:"10.5772/intechopen.100059",slug:"targeted-nano-drug-delivery-system-to-colon-cancer",totalDownloads:136,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cancer has been considered as the most cause of death in world. Employing of nanocarriers as drug delivery systems provide a platform for delivering drugs with increasing the anti-cancer efficacy, enhancing bioavailability of drugs, reducing side effects, enhancing the circulation half-life of drugs, improving the distribution of drugs and overcoming drug resistance. A number of nanocarriers have been studied as drug delivery systems for improving the treatment of cancer including liposomes, micelle, polymeric nanoparticles, carbon nanotubes, dendrimers, solid lipid nanoparticle (SLN) and nanostructure lipid carrier (NLC). In order to enhance recognition and internalization of nanocarriers by the target tissues, their surfaces can be modified with targeting ligands such as integrins, transferrin, folic acid, polysaccharides and antibodies. In this chapter, we are going to introduce the targeted nanocarriers for improving the cytotoxic action of drugs with further attempt of decreasing dose to achieve higher anticancer activity. Targeted nanocarriers would provide a promising therapeutic approach for cancer.",signatures:"Eskandar Moghimipour and Somayeh Handali",downloadPdfUrl:"/chapter/pdf-download/78844",previewPdfUrl:"/chapter/pdf-preview/78844",authors:[{id:"65036",title:"Prof.",name:"Eskandar",surname:"Moghimipour",slug:"eskandar-moghimipour",fullName:"Eskandar Moghimipour"},{id:"356504",title:"Dr.",name:"Somayeh",surname:"Handali",slug:"somayeh-handali",fullName:"Somayeh Handali"}],corrections:null},{id:"81238",title:"Artificial Intelligence in Healthcare: An Overview",doi:"10.5772/intechopen.102768",slug:"artificial-intelligence-in-healthcare-an-overview",totalDownloads:53,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The healthcare industry is advancing ahead swiftly. For many healthcare organizations, being able to forecast which treatment techniques are likely to be successful with patients based on their makeup and treatment framework is a big step forward. Artificial intelligence has the potential to help healthcare providers in a variety of ways, including patient care and administrative tasks. The technology aims to mimic human cognitive functions, as it offers numerous advantages over traditional analytics and other clinical decision-making tools. Data becomes more precise and accurate, allowing the healthcare industry to have more insights into the theranostic processes and patient outcomes. This chapter is an overview of the use of artificial intelligence in radiology, cardiology, ophthalmology, and drug discovery process.",signatures:"Syed Shahwar Anwar, Usama Ahmad, Mohd Muazzam Khan, Md. Faheem Haider and Juber Akhtar",downloadPdfUrl:"/chapter/pdf-download/81238",previewPdfUrl:"/chapter/pdf-preview/81238",authors:[{id:"255360",title:"Dr.",name:"Usama",surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad"},{id:"329248",title:"Dr.",name:"Md. Faheem",surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider"},{id:"252107",title:"Dr.",name:"Juber",surname:"Akhtar",slug:"juber-akhtar",fullName:"Juber Akhtar"},{id:"329247",title:"Dr.",name:"Mohd",surname:"Muazzam Khan",slug:"mohd-muazzam-khan",fullName:"Mohd Muazzam Khan"},{id:"463784",title:"Dr.",name:"Syed Shahwar",surname:"Anwar",slug:"syed-shahwar-anwar",fullName:"Syed Shahwar Anwar"}],corrections:null},{id:"78091",title:"Applications of Statistical Tools for Optimization and Development of Smart Drug Delivery System",doi:"10.5772/intechopen.99632",slug:"applications-of-statistical-tools-for-optimization-and-development-of-smart-drug-delivery-system",totalDownloads:165,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In the novel dosage form development, quality is the key criterion in pharmaceutical industry. The quality by design tools used for development of the quality products with tight specification and rigid process. The specifications of statistical tools are essentially based upon critical process parameters (CPPs), critical material attributes (CMAs), and critical quality attributes (CQAs) for the development of quality products. The application of quality by design in pharmaceutical dosage form development is systematic, requiring multivariate experiments employing process analytical technology (PAT) and other experiments to recognize critical quality attributes depend upon risk assessments (RAs). The quality by design is a modern technique to stabilize the quality of pharmaceutical dosage form. The elements of quality by design such as process analytical techniques, risk assessment, and design of experiment support for assurance of the strategy control for every dosage form with a choice of regular monitoring and enhancement for a quality dosage form. This chapter represents the concepts and applications of the most common screening of designs/experiments, comparative experiments, response surface methodology, and regression analysis. The data collected from the dosage form designing during laboratory experiments, provide the substructure for pivotal or pilot scale development. Statistical tools help not only in understanding and identifying CMAs and CPPs in product designing, but also in comprehension of the role and relationship between these in attaining a target quality. 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\r\n\tNowadays, all types of businesses ranging from the smallest e-com stores to the biggest corporations, use data to run operations. There are billions of bytes of data getting generated every minute. However, raw data doesn’t come in that handy on its own. There are many data management tools and applications. SQL or Structured Query Language is one of the programming languages which is used to communicate with the databases for the creation, deletion, and retrieval of data from it. The ability to use SQL will help you get more out of your data than just reading it. It can be used for ad-hoc data analysis and reporting and more extensive projects involving multiple tables and complex applications.
\r\n\r\n\t
\r\n\tSQL is worth learning because it’s a programming language that’s in demand in the tech industry and in other sectors that need technology. Most software developers who know SQL earn respectable salaries. Learning SQL can not only enhance your skills, but it can also give you a better understanding of the applications you work with daily. In this book, we will go through the details of SQL and how to use it effectively. The goal of this book is to have many practical application examples that will help learners easily acquire and self-study SQL.
In the context of this chapter, a satellite is a spacecraft (SC) that orbits around a celestial body such as the earth. A spacecraft has several design constraints placed upon it before it can be placed in an orbit around the intended celestial body. First, satellite designs are limited in their mass and volume to fit on the launch vehicle that places them into orbit. Secondly, the mass and volume limits affect the size of the power system on the spacecraft; therefore, the amount of power available to the satellite is also limited. In addition, the space environment (thermal, radiation, atomic oxygen, space debris, micrometeoroids, etc.) imposes constraints on the design such as parts and material selection.
A spacecraft is consisted of two parts: the spacecraft bus and the payload (PL) [1, 2]. The spacecraft bus provides control of the satellite and support services to the mission payload, while the mission payload provides the mission part of the satellite including payload control, mission data processing, and mission data downlink dissemination. Examples of mission payloads (or payloads or PLs) are: scientific instruments, remote sensing instruments, navigation service transmitters, or communications equipment. A satellite may have one type of PL or a combination of payload types to accomplish its mission such as navigation, remote sensing, and communications. Shown below in Figure 1 is a typical imaging satellite used for the remote sensing mission. Note the clear separation between the spacecraft bus that provides solar power and maneuvering capability via thruster, while the payload consisting of the camera and supporting communication devices such as antennas and guidance devices such as star trackers.
A typical satellite with bus and payload separation.
Regardless of the mission type1 and the payload that a spacecraft carries, a subsystem that must exist in all satellites is the communication subsystem that enables the spacecraft to communicate with the ground stations that control the satellite and to deliver the data that the mission requires. This chapter focuses on architecture and functionalities of the communications subsystem that usually resides on the satellite.
There are three specific segments shown in Figure 2 below that must work together for the larger overall system to provide communication, navigation, or any other type of missions:
The space segment consisting of all satellites and associated equipment required for the mission applications and the launch vehicles used to deliver those satellites to orbit.
The satellite control (or control) segment consisting of all the personnel, facilities, and equipment that are used to monitor and control all the assets in space. Practically, the control segment is also referred to as satellite ground segment because it is usually located on the ground.
The user segment consisting of all the individuals and groups who use and benefit from the data and services provided by the payloads of the satellite and the equipment that allows this use.
The three main segments for satellite system.
In general, the space mission dictates the type of orbit2, satellite design and its expected life cycle, and its operational scenarios. The PL design includes dimensions, interfaces, weight, physical characteristics, and basic utility needs (e.g., power consumption), which usually influences spacecraft (SC) bus design. The PL is often a unique and one-of-a-kind design tailored to meet specific mission requirements, frequently relying heavily on newer technology, while the satellite bus has the supporting function, and as such relies largely on existing or modified hardware such as batteries, inertial devices, and star trackers. Since PLs and their missions vary widely, so is this satellite bus supporting role.
Traditionally, the PL is considered a subsystem of the satellite bus that is designed to generally satisfy the corresponding mission requirements. The PL operational requirements sometimes impose specific requirements on the satellite bus that must be satisfied for the PL to accomplish its mission. This interdependence between satellite bus and PL subsystems has historically resulted in many nonstandard interfaces developed and implemented by the incumbent spacecraft builders. As a result, the aerospace industry has been moving toward a more standardized and commodity satellite bus framework that can potentially result in a tremendous cost saving approach.
As shown in Figure 3 below, a satellite bus typically consists of the following subsystems: command and data handling subsystem (C&DHS); communications subsystem (CS); electrical power subsystem (EPS); propulsion subsystem (PS); thermal control subsystem (TCS); attitude control subsystem (ACS) also known as guidance, navigation and control (GNC) subsystem; structures and mechanics subsystem (S&MS); and life support subsystem for manned missions if required. The C&DHS will be described in detail below. The CS provides the satellite bus with the necessary communication functionalities to connect the user and ground segments to different satellite subsystems. The EPS provides the electrical power generation and distribution for various spacecraft subsystems. The PS provides maneuvers necessary for altitude, inclination adjustment, and momentum management adjustments. The TCS provides active thermal control from electrical heaters and actuators to control temperature ranges of equipment within specific ranges. The ACS provides proper pointing directions for the satellite subsystems, such as sun pointing for EPS to the solar arrays and earth pointing for CS. The S&MS provides the necessary mechanical structure to withstand launch loads by the launch vehicle, during orbital maneuvers, as well as loads imparted by entry into the atmosphere of earth or another planetary body.
A typical satellite bus and payload subsystem.
On the other hand, a PL is tailored to a specific mission type. For example, a remote sensing satellite can have as its payload an electro-optical (EO) camera to take day-time pictures of the earth and then convert them to electrical signals that can be captured. Alternatively, the camera may also have infra-red (IR) sensors that enable the PL to see the earth at night, or microwave sensors that will let the PL “see” radio frequency (RF) signals from the earth at several radio frequencies (RFs). These sensors can be classified as passive or active, and each of them can be further classified as imaging or sounding3. Figure 4 below illustrates a generic imaging PL that will convert the sensor analog data into electrical signals that can be captured and transmitted to a ground station. Note the existence of a communication subsystem as part of this imaging payload.
A typical and generic sensor payload.
In this section, the different typical modules of a satellite communication subsystem are discussed. In addition, the command and data handling subsystem, and command, telemetry and mission data processing subsystem will also be described in detail.
At the physical layer, the communications subsystem starts with an antenna and the RF front-end transceiver. The antenna is the most important component of the communications subsystem where the electromagnetic (EM) signals are originated or received. The RF front-end/back-end is where the EM signal is being down/up-converted to baseband/RF signal to be demodulated/modulated for baseband signal recovery or downlink transmission, respectively. Figure 5 below depicts a typical transmitter and receiver (transceiver) chain with the modulation and demodulation (MODEM), followed by the RF front-end and the antennas. The baseband communications function is carried out by the MODEM, whereas the RF portion is handled in the transceiver, RF front-end, and antenna sections.
Typical RF front-end chain.
Modulation is the name given to the process of impressing the wanted signal to be transported onto a radio frequency (RF) carrier, which is then conveyed over the satellite link and demodulated at the receiving terminal to extract the wanted signal from the carrier. Thus, modulation translates a baseband spectrum (at zero frequency) to a carrier spectrum (at RF range) and demodulation is the process of recovering the data at the receiver end of the link. Thus, the process requires a modulator and a demodulator, collectively known as a MODEM. The input to the modulator may require some initial processing such as filtering and amplitude limiting.
Before the RF signal is sent to the antenna, a traveling wave tube amplifier (TWTA) or solid-state power amplifier (SSPA) is needed to amplify the RF signal to a desired level for transmission. Conversely, after the RF signal is received by the antenna, a low noise amplifier (LNA) is needed to ensure that the received signal is brought up to the desired signal level with minimum noise before demodulation.
In addition to being lighter than TWTA, the achievable power efficiency for SSPAs is a major factor to support transmit phased arrays. Currently, the tube-based TWTA implementations are still the most cost-effective design, even though both options might be viable for lower power systems.
In increasing technical maturation over the years, the following types of spacecraft antennas have been used for satellite communications:
Low-gain omni and squinted-beam antennas for large earth coverage.
Increased gain types of satellite antennas (horn type and helix antennas) for medium earth coverage.
Parabolic reflectors, including multi-beam antennas with multiple feed systems for multiple user and small area coverage.
Deployable antennas, particularly to achieve more highly focused beams and support much high-gain multi-beam antennas.
Phased array feed and phased array antennas for scanning and hopping beams.
Optical communications systems, which have been used for intersatellite links and interplanetary communications, and increasingly being considered for earth-to-space systems.
In general, there are many different types of antennas, but the one most commonly associated with satellite communications is the parabolic dish antenna. These dish antennas have a narrow beam width, concentrating the energy of the radiated main beam into a smaller solid angle. This means more of the radiated energy reaches, or “illuminates,” the satellite when using a dish antenna as compared to an omnidirectional, or “omni” for short, antenna. An example of dish antenna used on satellite is shown below in Figure 6 for a Ku-band space to ground antenna (SGANT) mounted on the external stowage platform of the International Space Station (ISS).
Example of a satellite dish antenna.
There are several factors driving the design and development of satellite antennas. These include the need to reuse frequency bands because of limited spectrum allocations; the need to have antennas that can operate at higher frequencies with higher bandwidth; and the desire to deploy higher gain antennas at the same time minimizing the required size, weight, and power (SWAP) constrains. In practice, there are substantially more SWAP constrains for satellite antennas than on the ground stations, and this results in several design trade-offs between the space and control/user segments.
For example, the GEO orbit allows a high gain antenna to be pointed at a satellite with a minimum of tracking. Thus, a large dish can be used and remain virtually stationary without tracking a satellite as it moves around in its orbit. On the other hand, a low earth orbit (LEO) satellite that can cross from horizon to horizon in a few seconds can result in ground antenna installations that can be quite complex and expensive. Consequently, trade-offs need to be made to support the mission parameters of the whole satellite network.
The term “command and data handling subsystem” (C&DHS) was referred to as “On-board Computer” (OBC), which is a legacy of the past in which many satellite functions were performed by analog circuits with the help of an OBC. With the current shift toward the digital domain, the term OBC does not fully cover the topic anymore thus C&DHS is being used instead. An appropriate analogy to describe the C&DHS subsystem is to regard it as the brain and nervous system of the spacecraft.
The function of a C&DHS subsystem is to perform onboard processing and operations and internal communication [3, 4]. The task of managing the operations of the spacecraft subsystems is nowadays performed mostly by software in an autonomous manner and is generally categorized as onboard operations. The software is also responsible for preparing the data to be downlinked and handling any commands that are received from satellite operators on the ground. Lastly, the C&DHS facilitates and controls all internal communications (consisting of commands, telemetry, and tracking data) between the different satellite subsystems. The basic functions of the C&DHS can be summarized below:
Receives commands from the command or user segment through the telemetry, tracking, and control (TT&C) subsystem.
Decodes, executes, and/or distributes those commands to/from the onboard computer.
Collects and formats telemetry data from all space vehicle (SV) units.
Distributes telemetry for downlinking. Provides a platform for bus flight software (FSW).
Additional functions include ranging processing for satellite tracking purpose, satellite timekeeping, computer health monitoring (watchdog), and security interfaces.
An overview of the architecture of C&DHS in a typical satellite is provided in Figure 7 below. In this figure, all components are connected to each other via a common low-speed data bus in red color, typically compliant with MIL-STD 1553 or other standards. Also shown is the data connection in blue from the C&DHS to other components, which is more customized and high-speed in nature depending on the design.
Block diagram of a typical command and data handling subsystem.
The heart of the system is the C&DHS’ onboard computer (or OBC) that runs the software responsible for managing the onboard operations. The OBC is tightly linked to the electrical power subsystem (EPS). The main reason is the importance of the available and consumed power for managing onboard spacecraft operations. For instance, by continuously querying the EPS on the available power, the OBC can decide to turn off non-critical subsystems to prevent vital systems from shutting down from lack of power. Secondly, the OBC must be able to command the EPS to disable or enable different subsystems throughout the various phases of the mission. Since the amount of transmitted data between these two subsystems is small, a low-speed data link is sufficient, although there is a new trend to incorporate high-speed standard link such as SpaceWire4 to satisfy increasing demand for data volume.
The OBC is also responsible for receiving, interpreting, and executing commands from ground operators via the radio receiver. Using low-speed radio transmitters, the OBC also sends packets of housekeeping data, or telemetry, to the ground station. The purpose of the housekeeping data is to give the operators on the ground an overview of the spacecraft health and its general condition.
Some small satellites only have a single low-speed transmitter, so the housekeeping and payload data are combined over the same link. For larger satellites with payloads capable of producing vast amounts of data, a dedicated high-speed data link is used to store the data on an onboard storage system. When the satellites pass over a ground station, the OBC commands the high-speed radio transmitter to retrieve and transmit the previously stored payload data through another dedicated high-speed link from the onboard storage system. This approach frees the OBC from having to process large amounts of data and allows it to devote its internal resources for time critical operations and communicates with the PL and all other subsystems through the low-speed data links. This would include the requirements to retrieve information on the health, perform critical interventions as well as to command these subsystems to perform various actions according to the operational arrangement of the mission.
The telemetry, tracking, and control (TT&C) subsystem of a satellite provides a connection between the satellite (space segment) and the ground facilities (control or user segment). The purpose of the TT&C function is to ensure the satellite performs correctly. As part of the satellite bus, the TT&C subsystem is required for all satellites regardless of the mission type. The TT&C subsystem has three specific tasks that must be performed to ensure a successful mission:
Telemetry: the collection, processing of health, and status data of all spacecraft subsystems, and the transmission of these data to the control segment on the ground. This requires not only a telemetry system on the spacecraft but also a global network of ground stations around the world, unless the satellite space network includes intersatellite links that can relay the data to designated satellite and downlink to the appropriate ground station. Figure 8 below illustrates the processing of telemetry data by the C&DHS. Here the different health information and status information sent from various subsystems are collected by the telemetry input interface, fed to the C&DHS processor, buffered, encrypted, and sent down to the ground station.
Tracking: the determination of the satellite’s exact location by the control segment and where it is going via the reception, processing, and transmitting of ranging signals. This requires a ranging system on the spacecraft and a data collection ground network for this tracking function to work.
Command and control: the reception and processing of commands for continuous operation of the satellite. Usually a ground system is required, although advanced spacecraft designs have evolved toward “autonomous operations” so that many of the control functions can be automated onboard and do not require ground intervention except under emergency conditions. A typical command processing scenario is illustrated in Figure 9 where serial command bit stream from the command receiver is received by the command input interface, where the relevant commands are extracted and sent to the appropriate subsystems via a serial or parallel interface.
Telemetry processing by C&DHS.
Command and control message processing by C&DHS.
For communications payload, the onboard switching systems are designed to make more efficient use of a satellite communication network, especially those that employ multi-beam technology that entails onboard switching to interconnect uplink and downlink beams with a high degree of efficiency.
Figure 10 below summarizes the functional block diagram of a channelized transponder processor assuming a digital implementation of the channelized transponder filtering and switching function. Any signal within the receiver bandwidth is down-converted to an intermediate frequency (IF) or baseband and digitally sampled. These samples are digitally filtered, stored, and routed to the switch port corresponding to the desired downlink beam. This routing is achieved by a simple readdressing of the stored digital samples within a common output buffer memory or by a more traditional digital switch implementation.
Channelized processor for communications payload.
For most sensing payload and as shown in Figure 4 above, the sensor analog data are collected onboard, digitized, buffered if necessary, and transmitted down to ground station for processing. This is due to the complexity of sensing mission data processing and the lack of onboard computational power to accomplish these tasks. An example of onboard PL processing for passive electro-optical (EO) remote sensing is shown in Figure 11 below, where the reflected light from earth is passing through a combination of optical lenses and charge coupled device5 (CCD) whose output is an analog signal that would be conditioned by analog filters before being digitized, compressed, and sent down via a mission data downlink to the ground station for processing. There, the data are decompressed, and image is enhanced by appropriate algorithms and displayed for users.
Onboard image processing for an EO application.
Typical data volume collected by sensing payload is large, and peak rates can produce data at much higher speeds than TT&C; thus, a separate downlink for mission data is needed. Depending on the system, this mission data downlink to a ground station can either be performed using a dedicated mission direct downlink, or indirectly via a relay broadband communications satellite. Sensing satellite can be positioned in GEO, MEO, or LEO orbits, and can have many possible mission data downlink architectures based on mission requirements. For example, a LEO sensing satellite can either buffer its mission data until within view of a dedicated ground station for downlink, or it can forward its mission data to a relay satellite that can ensure that the mission data can be downlinked to a designated ground station.
Another example of active remote sensing is a synthetic aperture radar (SAR) mission, where returned radar signals are collected onboard and sent to the ground to be correlated and form an image of the ground surface. This type of remote sensing does not heavily depend on sun light and other weather affects. Applications for SAR include agriculture, geology, geohazards, ice, oil spills, and flood monitoring. Several emerging applications such as forestry, ship detection, and others are possible [1]. An example of a SAR mission is the NASA-ISRO Synthetic Aperture Radar (NISAR) [5], which is a collaborative earth-science mission between NASA and the Indian Space Research Organization (ISRO). The sensing payload features an L-band SAR instrument and an S-band SAR instrument. The simultaneous dual-frequency radar system at peak rates will produce data at gigabit-per second speeds, which drives the data-volume requirements at a minimum of 35 Terabits per day of radar science data to the ground. This is a direct mission downlink system with three designated ground stations. The payload communication system uses a 70-cm high-gain antenna with two synchronized transmitters in a dual-polarization configuration with each transmitter providing 2.4 Gbps of coded data with an aggregate rate of 4.8 Gbps.
Traditional communications systems are designed for and constrained to a specific waveform(s) operating over predetermined frequencies, bandwidths, and signal modulation types. This paradigm works well when the requirements and constraints of the communication link and network protocol are well understood prior to design.
As a result, most radios in today’s world have very dedicated uses. A car key fob is designed only to unlock or lock your car door, while a smart phone radio connects to the Internet through various wireless communication protocols. Although these examples vary in complexity of the hardware, they both cannot operate outside the confines of their physical layer implementation. Consequently, RF hardware with a narrow focus is not suitable for applications with a broader communication scope.
A single software defined radio (SDR) with a flexible RF front-end combined with modern computing power can be used for the above applications plus more. In addition, a radio with a flexible hardware and software architecture can also lead to more innovation in the communications industry. Because of the rapid development nature of software, an engineer or researcher can experiment with novel ideas and SDR waveforms that would not be achievable with a traditional radio.
SDR in the satellite communications industry has become a growing trend, particularly in the commercial and defense industries. In the following section, an overview of SDR will be given and applications of SDR in satellite communications will be discussed.
Before going into SDR basics, some of the SDR advantages are [6]:
Interoperability: an SDR can seamlessly communicate with incompatible radios, or work as a bridge between them. For example, different branches of the military and law enforcement can use many incompatible radios, thus hindering communications during joint operations. A single multichannel SDR can work with all these different radios and provide interoperability.
Efficient use of resources under varying conditions: for example, a low-power waveform can be selected if the radio is running low on battery, while a high-throughput waveform can be used to quickly download a file. This flexibility is one of the first reasons why SDR became popular.
Opportunistic frequency reuse in SDR using cognitive radio6 (CR) technology: if the “owner” (or primary user) of a spectrum band is not using it, an SDR-CR can “borrow” the spectrum until the owner comes back. This technique has the potential to dramatically increase efficient use of radio frequency spectrum.
Reduced obsolescence: an SDR can be field upgraded to support the latest communications standards. This capability is especially important to radio with long life cycles such as those in satellite communications.
Lower cost: a single SDR can be adapted for use in multiple markets and for multiple applications. For example, a single radio can be sold to cell phone and automobile manufacturers to significantly reduce cost.
Research and development: SDR can be used to implement many different advanced waveforms, e.g., code division multiplexing access (CDMA) or orthogonal frequency division multiplexing (OFDM), for real-time performance analysis. Performance studies can be conducted much faster and often with higher fidelity than simulations.
On the other hand, some of the disadvantages for SDR are:
Cost is the most common argument against SDR. A single key fob is based on a very inexpensive ASIC7; however SDR is heavily reliant on FPGA,8 which is much more expensive. This is even more significant for high-volume, low-margin consumer products.
The second most common argument against SDR is increased power consumption with increased DSP complexity and higher mixed-signal/RF bandwidth. Power consumption in an FPGA or GPP for flexible signal processing can easily be 10 times higher than in ASIC. Also, wideband analog-to-digital converters (ADCs), digital-to-analog converters (DACs), and RF front-ends consume more power than their narrowband equivalents.
Increased time and cost to implement the radio: it can take much more engineering effort to develop software/firmware for multiple waveforms than for one, especially if it must be compliant with a military standard such as JTRS9.
Changing specifications and requirements: this usually happens when the SDR design must support not only a set of baseline waveforms but also anticipate additional waveforms.
Increased schedule risks: since SDR is still a relatively new technology, it is more difficult to anticipate schedule problems. Also, it is difficult to thoroughly test the radio in all the supported and anticipated modes.
Limited technical scope: SDR only addresses the physical layer and will require cooperation from upper layers for throughput improvements.
The general definition for a SDR is
A radio can be categorically separated into receivers and transmitters. For this section, the receiver implementation will be considered as it is generally more interesting and complex. A block diagram of an SDR receiver is shown below in Figure 12. The following sections will present the anatomy of the SDR that differentiates it from a traditionally designed radio.
A block diagram of an SDR.
The purpose of the RF front-end (RFFE) is to isolate the desired signal received by the antenna from interference signals. To achieve this, the signal of interest must be brought down to lower frequency for digital conversion while mitigating the side effects from filtering during the frequency conversion process. A flexible RFFE for SDR must be designed so that the frequency and bandwidth are controllable by software. Depending on the system requirements and the available RF component specifications, there are several ways to achieve this.
One of the most common RFFE designs for analog radios is the heterodyne receiver. A heterodyne receiver, shown in Figure 13 below, works by mixing down the received signal from its carrier frequency to a lower intermediate frequency (IF). The signal at IF can now be more conveniently filtered, amplified, and processed. A super-heterodyne receiver uses a fixed IF that is lower than the carrier frequency but higher than the signal bandwidth and often uses two stages of down conversion to reduce the filtering requirements at each stage.
Heterodyne receiver.
Another popular RF front-end architecture generally used for low-power applications is called zero-IF. A zero-IF receiver, shown in Figure 14 below, uses a single mixing stage with the local oscillator (LO) set directly to the desired carrier frequency to convert directly to baseband in-phase and quadrature signals. Because mixers tend to have high power consumption and only low-pass filters are required, the simpler zero-IF provides improved power efficiency over a heterodyne architecture. However, the zero-IF implementation is more susceptible to IQ imbalances of the in-phase and quadrature oscillators, which will produce anomalies in the signal constellation. LO leakage may also self-mix through the RF ports creating a large DC bias. Both issues can be corrected using digital signal processing.
Zero-IF receiver.
The analog-to-digital converter (ADC) is responsible for converting a continuous-time signal to a discrete-time one. To translate signals from the analog to digital domain, an ADC must perform two fundamental steps: sampling and quantization. Sampling is the process of reading voltages at discrete-time intervals. Quantization is the process of converting these voltage readings into binary outputs. ADC performance can be evaluated based on various parameters, such as: signal-to-noise ratio (SNR), dynamic range, bit resolution, sampling rate, and power dissipation. The ADC dictates the DSP limitations of the SDR. Generally, the sampling rate should be at least twice the desired bandwidth of your signal. The ADC should be chosen to match the capability of your processor and specifications of the signals of interest.
The two main functions of a digital front-end are sample rate conversion (SRC) and channelization. Once a signal has become digitally converted, the samples need to be further primed for digital processing. Operating the ADC at a fixed rate simplifies its clock generation; however, it may be necessary to convert the sampling rate to match the sampling rate required to demodulate certain waveforms. Most wireless signals generally operate with specific symbol or chip rates that are specified by their respective standard. Depending on the RFFE design and signal type, channelization may be required to select the channel of interest.
SRC represents a classic sampling theorem problem. Converting sampling rates can introduce undesirable effects such as aliasing, an effect that causes frequency components to overlap. SRC can be achieved digitally through the processes of decimation and interpolation. To mitigate aliasing, decimation is performed by using an anti-aliasing filter followed by subsampling, which is essentially removing samples at certain intervals. Interpolation is a method of calculating values to add values in between samples. Channelization works by using digital down conversion, the process of digitally mixing down a signal to baseband with a numerically controlled oscillator.
SDRs have an array of devices to choose from for the required DSP application, each with their own strengths and weaknesses. An SDR may integrate multiple processor types and partition the signal processing chain to optimize each processor. The following criteria should be considered when evaluating the various processor types: flexibility, modularity, and performance. The three digital hardware choices this section will consider are the general-purpose processor (GPP), digital signal processor (DSP), and the field programmable gate array (FPGA).
A GPP is the typical microprocessor designed to handle a wide variety of generic tasks that can be found in your everyday personal computer. They are generally designed to have large instruction sets and highly capable of implementing and performing complex arithmetic tasks such as modulation/demodulation, filtering, fixed/floating point math, and encoding/decoding. Some commonly used GPP architectures are x86/64 and Advanced RISC Machine (ARM). The advantage of using a GPP is the wide availability, flexibility, and ease of programmability. Several GPP-based SDRs, such as Universal Software Radio Peripheral (USRP) and the LimeSDR, operate by digitizing the baseband signal and performing the required digital signal processing on computers. These types of SDRs are popular among university researchers and hobbyists due to the relative ease of obtaining and developing their applications.
Because the GPP was designed with such a broad focus, latency, speed, and power efficiency may be a limiting factor depending on the application. Many wireless communication standards have strict real-time and large processing bandwidth requirements that most modern CPUs cannot meet due to processor architecture and operating system design. .
A DSP is a microprocessor optimized for digital signal processing applications with the ability to be programmed with high-level languages. Although a GPP can contain much of the same functionality, the DSP performs the same digital signal processing operations more quickly and efficiently due to its reduced instruction set computer (RISC) architecture and parallel processing. The reduced instruction set limits the essentials but contains optimizations for common DSP operations such as multiply accumulate (MAC), filtering, matrix operations, and fast Fourier transform (FFT). DSPs are commonly sold in two variants: optimized for power efficiency and optimized for performance; and are used in applications such as base stations and edge devices. Power consumption is also minimized by reducing the silicon footprint that would be in GPPs sophisticated cache and peripheral subsystems.
Although DSPs have been commonly deployed in the past decades, they serve as a middle ground between GPPs and FPGAs with regard to flexibility, performance and efficiency. Field-programmable gate array (FPGA) offers more parallelism, higher data rates, and better power efficiency than DSP, but is not well suited for control applications, such as implementing the network/protocol stack. This is due to the limited amount of memory in FPGA and for this reason it is often paired with GPP.
A FPGA is an array of programmable hardware logic blocks, such as general logic, memory, and multiplier blocks, that are wired together via a reconfigurable interconnect to generate an integrated circuit for several designs with the ability to quickly switch between configurations. FPGA configurations are programmed using hardware description language (HDL), which is also used for ASIC. Because a FPGA functionality is defined at the hardware level and can be implemented using parallelism, it can perform DSP algorithms at much higher rates than DSPs and GPPs. FPGA consumes more power and requires more space than ASICs but provides more programmability and flexibility than ASIC. A big consideration for using FPGAs for SDR is the domain knowledge requirement for developers. Developing on FPGAs can be time consuming and require an extensive understanding of the target hardware architecture.
When the system requirements exceed the capabilities of a singular processor type, a comprehensive solution may include a combination of the above processor types. A common processing architecture in the defense industry comprises of a FPGA, DSP, and GPP. In this paradigm, the FPGA is responsible for high data rate signal processing tasks, such as sampling and filtering, the DSP handles demodulation and protocol, and the GPP performs control-related tasks, such as the user interface and algorithmic processing. Implementing such a system can become a complex management task to coordinate the processing flow; however, the system can benefit greatly by optimizing overall performance based on the strength of each processor.
For space applications, SDR has unique challenges such as extreme radiation and temperature environment, autonomous operational requirements, limitations on size, weight and power (SWAP), and the need for reduced development time and increased reliability in agile prototyping. In this section, recent applications of software defined radio to satellite, as well as the current status of radiation-hardened SDR components, are presented.
Recognizing early on that a standard and open architecture is needed to encourage reuse and portability of software, NASA developed an open architecture specification for space and ground SDRs called the Space Telecommunications Radio System (STRS) [9]. From this standard, several compliant systems have been built and demonstrated in radios on the International Space Station (ISS) and several ground stations. It was also the intention of NASA that the STRS architecture should be used as baseline for many future NASA space communications technologies.
In a nutshell, the STRS standard consists of hardware, configurable hardware design, and software architectures with accompanying description, guidance, and requirements. The three main hardware functionalities are connected by the Hardware Interface Description10 (HID) and described and shown in Figure 15 below:
General processing module (GPM) consists of the general-purpose processor; appropriate memory; spacecraft bus (e.g., MILSTD-1553, Space Wire); interconnection bus (e.g., PCI); and the components to support the configuration of the radio.
Signal processing module (SPM) where signal processing is used to handle the transformation of digital signals into data packets. Its components include ASICs, FPGAs, DSPs, memory, and connection fabric/bus (e.g., PCI, flex-fabric).
RF module (RFM) handles the RF functionality to transmit/receive the appropriate digital signal. Its components include RF switches, digital-to-analog converter (DAC), analog-to-digital converter (ADC), diplexer, filters, low-noise amplifiers (LNAs), and power amplifiers (PAs).
NASA STRS’ three main hardware functionalities.
In STRS terminology, software includes source code, object code, executables, etc. implemented on a processor. As shown in Figure 16, the STRS software architecture uses three primary interfaces: the STRS APIs, STRS hardware abstraction layer11 (HAL) specification, and the Portable Operating System Interface12 (POSIX®). The STRS APIs provide the interfaces that allow applications to be instantiated and use platform services.
STRS software architecture layers.
Configurable hardware designs are the items and designs, such as hardware description language (HDL) source, loadable files, data tables, etc., implemented in a configurable hardware device such as a FPGA.
STRS encourages the development of applications that are modular, portable, reconfigurable, and reusable. The STRS software, configurable hardware design, metadata, documentation for STRS applications, STRS devices, and operating environments (OEs) are submitted to NASA STRS Application Repository to allow applications to be reused in the future with appropriate release agreements.
CubeSats13 are increasingly popular spacecraft platforms for mission-oriented experiments that can be accomplished via quick prototyping and launches [10, 11, 12]. This short development timeline is due to the use of commercial-off-the-shelf (COTS) technology that typically has limited resilience to the space environment. Therefore, CubeSat usage has largely been limited to experiments or applications where high availability is not the main objective.
In general, SDR technology will allow for on-orbit flexibility via reconfigurability of data management, protocols, multiple access methods, waveforms, and data protection. SDR processing requirements are inherently scaled to the application. The availability of modular, high-performance sequential and parallel processors that are resilient to radiation upsets allows the tailoring of hardware architectures to the application and to the CubeSat platform. This is especially suitable for missions that require the flexibility to support multiple TT&C and mission data from multiple satellites and ground stations [13, 14, 15].
Given the provided mission flexibility, implementing an SDR on a CubeSat could significantly increase the required processing capacity and thus the size, weight, power and cost (SWAP-C) of the SDR implementation. Consequently, most current CubeSat SDR design and implementation are still customized depending on the mission requirements. In [16], some of the current COTS SDR hardware and software platforms such as GomSpace, Ettus Research USRP, EPIQ Solutions, Lime Microsystems, FunCube, and RTL SDR are described and categorized in decreasing cost and mass to illustrate the heterogeneous nature of SDR in CubeSat applications. Also described are a number of space and ground segment systems built to be (or have been) launched using these COTS SDRs or components thereof. What would be needed is a standard for CubeSat SDR similar to NASA STRS to ensure that hardware and software reuse can be incorporated into future CubeSat developments.
A pioneering commercial application of SDR in space is the HawkEye 360 (HE360) system [17] that was launched on 3 December 2018. HE360 system consists of three identical spacecrafts and their primary payload is a SDR with custom RF front-end along with VHF Ku-band antennas. This Pathfinder mission14 was to enable onboard reception and geolocation of different types of terrestrial RF signals using signal processing technique to combine received data from all three payloads15.
One commercial application of this mission is the detection and geolocation of a maritime vessel’s automatic identification system (AIS), which broadcasts the locations generated by GPS-enabled receiver. The locations generated by AIS can be disabled or spoofed, therefore not reliable. Another application would be to allow regulators, telecommunications companies, and broadcasters to globally monitor spectrum usage and identify areas of interference. The system can also be used to help large area search and rescue operations by quickly locating activated emergency beacons.
The SDR developed for the Pathfinder payload consists of an embedded processor system and three baseband processors. The baseband processor was built around the Analog Devices 9361 (AD9361) System on Chip (SoC) product, which is a highly integrated RF transceiver that combines high-speed ADCs and DACs, RF amplifiers, filtering, switching plus more. The HE360 payload supported up to three receiver channels (one AD9361 per channel) that can be simultaneously processed on separate frequencies. In addition, the signal processing subsystem takes advantage of open-source software and firmware code to allow system development to proceed without knowing the final space hardware. GNURadio16 was selected for being a free and open-source toolkit for SDR and widely used in small space projects for ground software processing.
In space, most semiconductor electronic components are susceptible to radiation damage, thus radiation-hardened (or rad-hard) components are required and normally developed based on their COTS equivalents with variations in design and manufacturing17 to reduce the susceptibility to radiation. Consequently, rad-hard components tend to lag behind most recent COTS developments. Depending on mission requirements, rad-hard products are typically selected and tested using popular metrics such as total ionizing dose18 (TID), and single event effects19 (SEEs).
Per US DoD MIL-PRF-38535 J standard [18], an ideal integrated circuit for space applications is the qualified manufacturing line20 (QML) Class V with radiation hardness assurance21 (RHA) level identified in the part specification. From the perspective of payload designer and developer, only Class V is space quality and should be the main factor for selecting SDR hardware components.
The FPGA is perhaps the most important component of an SDR and has a long history for manufactured QML class V parts where rad-hard Xilinx and Actel (now Microsemi) FPGAs were studied [19]. Currently, Xilinx is the major player for space-qualified QML level V products used in actual payloads with many more devices under development. The rad-hard DSP products also follow the QML process, with Texas Instrument (TI) currently taking the lead for in-flight payloads with many offerings in space-qualified RF components in addition to DSP. Similarly, space-qualified GPP follows the same QML path as FPGA and DSP, and the current on-flight rad-hard GPPs based on the following architecture are [20].
RISC PowerPC: RAD750, RAD5500.
RISC MIPS: RH-32, Mongoose-V, KOMDIV-32.
Motorola 68,000 Series: Coldfire M5208
ARM Microcontroller: Vorago VA10820
In the first section of this chapter, an overview of the satellite bus and payload subsystems are presented for command and data handling subsystem (C&DHS); communications subsystem (CS); electrical power subsystem (EPS); propulsion subsystem (PS); thermal control subsystem (TCS); attitude control subsystem (ACS) also known as guidance, navigation and control (GNC) subsystem; and structures and mechanics subsystem (S&MS). A significant portion is spent on describing the C&DHS and CS with much details on how they are related to other satellite subsystems for continuous operation.
There are distinctive functional separations between the satellite bus and payload that are discussed at a high level with some examples given; however, there are currently no existing standard on their interfaces due to legacy satellite design and development. Examples were given for mission-specific sensing and communications payloads, showing that pretty much all mission payloads are very customized in design in legacy systems.
The second section of this chapter covers software defined radio (SDR) as a new technology with an overview and how SDR is being applied to satellite design and development in both space and ground segments. There has been a NASA standard for SDR that has been used for traditional and large satellites and shown to have some advantages over non-SDR approach.
However, recent rapid developments of Small Satellites (SmallSats), which CubeSat is a subset of, have resulted in an explosion of SDR applications to build Pathfinder missions that can lead to successful follow-on projects. There remains to be a standard to be defined for SDR for this CubeSat application. Regardless, SDR is providing a path forward to a common framework that may enable a more generic building block for a future concept called Software Defined Satellite that will change missions based on a software upload.
Since SDR is becoming an important part of a satellite, radiation hardening of the relevant SDR components is described in some detail. The area is evolving slowly despite fast changing technology due to the additional design and manufacturing steps taken to ensure minimum effects of radiation on microelectronics. The selection of the appropriate rad-hard FPGA, DSP, and GPP components should be an important factor in design trade-offs when SDR is being considered for future missions.
The first author, Dr. Hung H. Nguyen, would like to express bountiful appreciation for his wife, Thuy Le Nguyen, for her constant support during this effort.
Ovarian sex cord-stromal tumors (SCST) are a clinically significant group of uncommon neoplasms that represent approximately 8% of ovarian cancers. They are thought to arise primarily from the gonadal sex-cord (granulosa and Sertoli cells) and/or gonadal stromal cells (theca cells) [1]. Malignant ovarian tumors are a group of morphologically, genetically and functionally distinct diseases, but associated with the same organ, the ovary. Epithelial ovarian cancers (EOC) represent the majority of ovarian cancers (accounting for 85–90%), the other two primary classifications are the SCST and the rarer germ cell tumors [2]. Ovarian SCST are primarily classified histologically as granulosa cell tumors (GCT), Sertoli stromal tumors and SCST of mixed or unclassified cell type, theca-fibroma. In the most recent World Health Organization (WHO) classification of female reproductive tract tumors, SCSTs are separated into pure stromal, pure sex cord and mixed SCST [3] with the sub-classifications of these groups as shown in Table 1. GCT are the most common accounting for approximately 90% of all malignant SCST. The clinical and molecular features of GCT has been extensively reviewed by Jamieson and Fuller [2]. Although recurrent and advanced stage GCT are associated with a very high mortality [2], they remain a relatively neglected subset of tumors. The high mortality rate of advanced disease has not been helped by the tendency to group these ovarian cancers with EOC, and apply treatment regimens that are based on therapeutic approaches for EOC, rather than tailoring treatment to the specific SCST [2]. Thus, understanding the genetics and hence the biology of these distinct tumors has an immediacy beyond just understanding tumor biology, with targeted therapeutics urgently needed for women with SCST. In this review we will provide an overview of studies that explore insights into the genetics and genomics of these tumors, with the aim to seek to identify key unanswered questions.
A. Granulosa-stromal cell tumors 1. Granulosa cell tumor a. Adult granulosa cell tumor b. Juvenile granulosa cell tumor 2. Tumors in the thecoma-fibroma group a. Thecoma i. typical ii. luteinized b. Fibroma c. Unclassified B. Sertoli–Leydig cell tumors 1. Well-differentiated a. Sertoli cell tumor b. Sertoli cell tumor with lipid storage c. Sertoli–Leydig cell tumor (tubular adenoma with Leydig cells) 2. Moderately differentiated 3. Poorly differentiated (sarcomatoid) 4. Retiform with heterologous elements C. Gynandroblastoma D. Unclassified |
Granulosa cell tumors (GCT) of the ovary are the most common type of SCST, accounting for approximately 5% of all ovarian cancers [4]. GCT are subdivided into two types: the more common adult (aGCT) and the rarer juvenile (jGCT) form. The jGCT subtype represents approximately 5% of all GCT. The two subtypes have different etiologies, and classification for either are not based on age alone as either tumor type can occur at any age. GCT arise from the granulosa cells (GC) of the ovarian follicle, and exhibit many features of normal GC, including expression of the follicle stimulating hormone (FSH) receptor gene, estrogen synthesis, ERβ expression, inhibin subunit expression with synthesis of biologically active inhibin, and anti-Müllerian hormone (AMH) expression [2]. Their presentation may include endocrine manifestations such as features of estrogen excess in prepubertal girls and postmenopausal women. The gonadal peptides inhibin and anti- Müllerian hormone (AMH) can be used in diagnosis and more specifically as tumor markers [2]. Studies from our laboratory as well as those of others have examined gene expression and signaling pathways involved in GC development, and have provided compelling support that not only are GC the cell type of origin for GCT, but that GCT also have consistent features with proliferating GC of the early antral follicle [5].
GCT are classified as low-grade malignancies, that are commonly detected at an early stage, providing a relatively favorable prognosis due to their overt clinical symptoms and indolent course. However, GCT have an unusual propensity for fatal late relapse, ~80% of women with aggressive or recurrent tumors will succumb to the disease [6]. At present, there are no standard methods for predicting relapse, no efficacious targeted therapies (aside from surgery) and no comprehensive understanding of the exact etiology of this disease.
Ovarian fibromas are the most common benign solid ovarian tumors, they represent 4% of all ovarian tumors. They are well-circumscribed masses that encompass spindle-shaped fibroblastic cells and abundant collagen bundles [1]. Ovarian fibromas can occur at any age but usually after menopause and rarely before 30 years old. The most common recommended treatment is surgery [7, 8]. However, preoperative diagnosis is often difficult due to their solid nature and the lack of specific clinical signs which can result in misdiagnosis as uterine myoma [8, 9]. Ovarian fibromas can also be associated with hydrothorax and ascites causing Meigs’ syndrome, a rare condition which is usually misdiagnosed as a malignant myoma [9, 10].
Ovarian thecoma was first described by Loeffer and Priesel in 1932 who observed that these tumors resembled thecal cells, lutein cells and fibroblasts [11]. Thecoma accounts for 0.5% - 1% of all ovarian cancers. It occurs in mostly postmenopausal women with a mean age of 59 years with only 10% of patients younger than 30 years [12]. Thecomas can be divided into two main types; typical or luteinized, which are thecomas that contain steroid-type cells resembling luteinized theca and stromal cells [12]. The most common symptom experienced by patients is postmenopausal bleeding [13]. The tumors range in size from small to solid masses larger than 15cm [12]. Burnandt
Sertoli–Leydig cell tumors (SLCT) also called androblastomas and arrhenoblastomas, exhibit cellular and molecular markers consistent with a dysgenesis of the ovarian stromal cells, reminiscent of disorders of gonadal dysgenesis [14]. They are rare, accounting for less than 0.5% of all ovarian cancers [3] and can occur in women of all age groups, but they are more often encountered in women under 40 years of age [15]. Patients usually present with symptoms related to androgen excess but can also present with estrogenic manifestations or have an asymptomatic clinical profile. SLCT are typically unilateral tumors and over 97% are diagnosed at Stage 1 [3, 15]. The prognosis is correlated with the degree of differentiation and stage of the tumor with the five year survival rate of well differentiated SLCT being ~100% [3]. In contrast to GCT, patients with SLCT relapse early, approximately two to three years following initial diagnosis [16]. Many SLCT are associated with somatic or germline mutations in a gene encoding an RNase III endoribonuclease, DICER1, which is involved in the generation of microRNAs (miRNAs) that modulate gene expression at the post-transcriptional level [17, 18, 19, 20]. Some studies have reported that 60% of SLCT harbor a DICER1 mutation [21], whereas others have reported that up to 97% of SLCT are DICER1 related [22]. It has been suggested that up to 100% of moderately and poorly differentiated SLCT have DICER1 mutations [17]. A whole exome sequencing study of 17 Chinese patients found somatic mutations in CDC27 (52.6%), DICER1 (21.1%) and MUC22 (21.1%) [23]. Germline and somatic mutations of DICER1 were higher in patients who were younger than 18 years than those in older patients [23].
Taking into consideration that the majority of patients presenting with SLCT are premenopausal with well differentiated tumors at an early stage, fertility sparing surgery with the removal of the affected ovary is recommended [21]. More aggressive surgery and chemotherapy is considered in patients with advanced stage or stage 1 patients with the presence of risk factors such as intermediate and poorly differentiated tumors, heterologous elements, increased mitotic rate, rupture or spillage of the tumor or presence of metastatic tumor [16].
The term gynandroblastoma was coined in 1930 by Robert Meyer, who deemed them as an extremely rare variant of SCST comprising of both ovarian (granulosa cell) and testicular (Sertoli cell) histological features [24]. These low-grade hormonally active tumors may also exhibit morphological evidence of stromal theca cells and luteinized cells resembling Leydig cells [24]. Since their first description, only a further 29 cases have been documented [25]. Based on the exceedingly low prevalence of gynandroblastomas, it appears they have a relatively benign disease course [26].
Currently, molecular insights into the histogenesis and pathogenesis of gynandroblastomas are lacking, but it has been postulated that they originate from a single progenitor cell that undergoes differentiation into both female and male elements [27]. This tumor type also shares many clinicopathologic features with other SCST including GCT and SLCT, as previously reported by Jang et al. [26]. Patients typically present with hormonal dysfunction with either estrogenic or androgenic symptoms [28].
The diagnostic criteria for this tumor type stipulate that either Sertoli-Leydig or granulosa cells should comprise at least 10% of the entire tumor mass [29]. There are several sex cord-stromal cell related immunohistochemical markers that exists to facilitate differential diagnoses including inhibin, calretinin, SF1 and CD56, however these are not specific to gynandroblastomas [29]. Other useful diagnostic markers include MART-1/melan-A [30] (specific to Sertoli-Leydig cell and steroid cell tumors), and the cell regulatory protein 14–3-3 sigma [28] (specific to GCT and steroid cell tumors). Further characterization of the molecular pathways mediating the development of gynandroblastomas as well as comprehensive histologic and genetic studies are required.
Peutz-Jeghers syndrome (PJS) is associated with ovarian SCST that have histological appearance that is intermediate between GCT and SLCT [31]. The majority of cases are caused by autosomal dominant germ line mutations in the
LKB1 activates AMP kinase (and its 13 superfamily members), regulating multiple biological processes such as cell polarity, cell cycle arrest, embryo development, apoptosis, and bioenergetics metabolism. LKB1 has become recognized as a critical tumor-suppressor gene that is frequently mutated in a broad spectrum of human cancers. As a tumor suppressor, a number of studies have shown the contributions of the genetic loss of LKB1 to tumorigenesis. The role of LKB1 in controlling cell metabolism through AMPK signaling has been widely documented. The LKB1-AMPK axis controls lipid and glucose metabolism, and acts as a negative regulator of the Warburg effect with the consequence of suppressing tumor growth [34]. Patients with PJS present with gastrointestinal hamartomata, polyposis and both benign and malignant tumors of various organs together with pigmentation of the lips, buccal mucosa and digits [35]. Neither loss of heterozygosity (LOH) at chromosome 19p13.3 nor mutations in the
Ollier disease (OD) and Maffucci syndrome (MS) are both subtypes of enchondromatosis and are considered rare nonhereditary skeletal disorders [38, 39, 40, 41, 42, 43, 44], with an estimated prevalence of 1 in 100,000 individuals [45]. They are characterized by multiple enchondromas (benign cartilaginous tumors) and when accompanied with additional subcutaneous soft tissue hemangioma, the condition is referred to as MS [45, 46]. Both disorders can lead to swollen extremities, joint deformities, limitations in joint mobility, scoliosis, and other bone anomalies [47].
OD and MS have been linked to ovarian jGCT, the first reported case of this association dates to 1972 [48], and since that time, a further 16 additional cases have been documented [49, 50]. In 2011 Amary
As previously mentioned, studies of changes at a genomic level in ovarian SCST have largely been restricted to aGCT. In contrast to EOC, GCT have a relatively stable karyotype [55]. Cytogenetic analysis [56] and comparative genomic hybridization (CGH) [57] studies have revealed trisomy of chromosomes 12 and 14 in approximately one third of aGCT cases and a similar percentage of monosomy of chromosome 22 [56, 57]. Between 5% and 20% of aGCT are aneuploid, however, neither the karyotype nor ploidy provides prognostic information [56, 58, 59, 60]. Mutations of lesser frequency have been observed at other loci, again providing no prognostic significance.
In a study by Caburet
For other SCSTs, reports of cytogenetic analyses are extremely scarce. A recent clinical case report describes three patients, from two unrelated families, with 14q32 deletions encompassing the DICER1 locus. Two of these patients have a history of DICER1-related tumors, including a 15-year-old female with a SLCT [64]. For thecoma-fibromas, a report by Streblow
Juvenile GCT (jGCT), as with aGCT, exhibit macroscopically a mixture of solid and cystic components with hemorrhagic areas. Thus, it is difficult to differentiate jGCT and aGCT by radiologic and morphologic findings. However, their histology differs from aGCT with a follicular or diffuse pattern of larger luteinized cells [69]. JGCT follicles have various sizes and shapes containing basophilic secretions. The cells have rich eosinophilic and/or vacuolated cytoplasm (indicating luteinization) and indistinct cell borders. They contain round, hyperchromatic or markedly bizarre nuclei which lack the nuclear grooving characteristic of aGCT [2, 69]. Unlike aGCT, Call- Exner bodies are not a feature of jGCT. The mitotic rate is high with marked nuclear atypia [2, 26]. Although the histologic appearances are therefore more ‘aggressive’ than for aGCT, the prognosis is generally better. The distinction between aGCT
The gene expression profile of GCT are similar to an FSH-primed proliferating preovulatory GC [5]. FSH stimulation of GC growth is mediated by the FSH receptor, a G-protein-coupled, seven-transmembrane domain receptor. We and others have hypothesized that activation of these pathways, perhaps through activating mutations in these signaling molecules of the FSH signaling pathway, may play a role in the pathogenesis of GCT as is common in other endocrine tumors [2]. Despite extensive investigations, this does not appear to be the case for aGCT. However, mutations were found in the
In addition, it has been postulated that as the FSH receptor signals through the oncoprotein AKT, that mutations in this signaling pathway may contribute to the pathogenesis of jGCT [75]. Indeed, in one study,
Many cancers develop from somatic mutations in driver genes that occur sporadically during replication or as a result of environmental factors and are not inherited. It is therefore important for the development of new therapeutic techniques to identify and consider how somatic mutations accumulate in caner genomes. In 2009, Shah
The presence of the FOXL2 C134W mutation provides a clear distinction between jGCT and aGCT. In jGCT, FOXL2 expression is low or absent [70, 77], whereas in aGCT expression levels in tumors bearing the mutation are generally consistent with levels seen in the normal ovary [70]. FOXL2 expression in heterozygous tumors appears equivalent for the wild-type and mutant FOXL2 alleles. In jGCT, low or absent expression of FOXL2 is associated with aggressive disease and carries a poor prognosis. The presence of the FOXL2 C134W mutation provides a molecular diagnosis of aGCT which has proven helpful in resolving the diagnosis of aGCT in histologically ambiguous or problematic cases [70, 71, 72].
FOXL2 plays a fundamental and essential role in ovarian development; its biology has been extensively studied [78, 79, 80]. It is a member of the forkhead box (FOX) family of evolutionarily conserved transcription factors. The C134W mutation is predicted to lie close to, but not in the DNA-binding domain [55]. Despite an extensive understanding of the biology of FOXL2 [78, 79, 80], the mechanisms of the tumorigenesis mediated by this somatic mutation in aGCT remain to be clearly established.
Although the majority of aGCT are stage 1 tumors and cured by surgical resection, those who have advanced stage disease or recurrent disease carry a poor prognosis [2]. As the FOXL2 C134W mutation is present in the vast majority of all aGCT, it does not explain differences in stage or behavior. It may be, as with certain inherited mutations, e.g., the ret. proto-oncogene in medullary thyroid cancer [82], that the transition from ‘hyperplasia’ induced by the somatic mutation to frank malignancy requires a second independent hit. Evidence to date indicates that this second event may be less specific than the first. In the case of aGCT, the genomic changes described above may for instance reflect the ‘second hit’ that results in aggressive clonal expansion. The subsequent somatic mutations that presumably drive tumorigenesis, recurrence, aggressive behavior, transcoelomic spread and metastatic disease still remain to be fully elucidated.
Evidence provided by recent transcriptomic studies have elucidated the genes whose expression has been modified, in some instances, may reflect genomic rearrangements. Gene expression microarray was used by Benayoun
Our laboratory has generated transcriptomic profiles between a cohort of six stage 1 and six stage 3 aGCT patients using a gene microarray approach to reveal significant differential gene expression between early and advanced stages. All of the aGCT samples were sequenced and also found to be heterozygous for the FOXL2 C134W mutation [83]. A total of 16 genes were reported as highly abundant in the advanced aGCT, with a further 8 genes found to be more highly expressed in the stage 1 aGCT (p value <0.05, >2fold-change). Curiously, two genes associated with malignancy were found to be highly expressed in the advanced stage aGCT, a member of the cytokine family called CXCL14 (chemokine C-X-C-motif ligand 14), and a multifunctional secretion protein called MFAP5 (microfibrillar-associated protein 5 transcript variant 1), which were 40- and 26-fold higher, respectively. Of the genes whose expression was high in the stage 1 aGCT, INSL3 (insulin-like 3 transcript variant 2) gene expression was 75-fold higher in stage 1 aGCT and provided robust discrimination of the two groups [83]. Whether INSL3 inhibits tumorigenesis or whether the diminished expression in advanced stage disease is simply a marker of de-differentiation of the tumor remains to be determined. Applying Gene Set Enrichment Analysis (GSEA) to these data sets [83] showed increased expression of genes on chromosome 7p15 in the stage 3 aGCT, which is consistent with the report of Lin
Aside from the identification of the FOXL2 C134W mutation in GCT, there have been several studies that have aimed to identify genomic alterations through sequencing candidate genes and known oncogenes [2]. Genes commonly mutated in other malignancies such as p53, PI3K, RAS and BRAF, are not a feature in GCT, and thus, putative ‘second-hit’ mutations still remain to be identified. But specific. The approach taken by The Cancer Genome Atlas project (TCGA) where a defined cohort of tumors are subjected to a full suite of genomic analyses [84] has yet to be applied to aGCT or indeed to other ovarian SCST.
The critical challenge to be addressed as a precursor to both improved prognostication (predicting recurrence) and identification of GCT-specific therapeutic targets (to address the high mortality of advanced disease) is to identify the molecular drivers of GCT pathogenesis beyond the aetiologic FOXL2 mutation.
In our own whole exome sequencing (WES) study, DNA from 22 fresh frozen, FOXL2 C134W mutation-positive GCT (14 stage 1 and 8 stage 3) was sequenced [85]. The analysis identified on average 64 coding and essential splice-site variants in each tumor, however recurrent mutations were not identified in individual genes or in related genes. The genes that were identified to contain truncating (stop, gain or frameshift) mutations, essential splice site mutations, non-synonymous mutations and stop/loss mutations in the stage I (970 variants) and recurrent (434 variants) tumors, were subject to variant effect pathway analysis. The canonical pathways identified were linked to DNA replication and/or repair as might be expected in malignancy; and to signaling through the epidermal growth factor receptor (EGFR) family. We also identified a high frequency of a TERT promoter mutation (see below).
Hillman
Zehir and colleagues determined the mutational landscape in tumors from 10,000 patients using their targeted MSK-IMPACT panel of 341 cancer associated genes; within this study, there were 11 FOXL2 mutation–positive GCT (two primary and nine “metastasis”) [87]. They identified mutations in 17 (5%) of the 341 cancer-associated genes on the array in these GCT samples; in only four of these genes was the mutation also found in our WES study [85].
In a recent study by Pilsworth
In another study, TP53 mutations were identified in 9.1% of patients, with higher tumor mutational burden and mitotic activity [90]. These findings suggest that tumors harboring TP53 mutations may be a high-grade subgroup of aGCT. It is noteworthy however, that other studies have not observed mutations in TP53 at similar frequencies [2, 88].
Indeed, the lack of overlap in the mutational variants identified in these various studies is curious. Also, somewhat surprising is the very limited number of recurrent mutations in specific genes, given that, by many criteria [83, 91], including the pathognomonic mutation in the FOXL2 gene [70], GCT are remarkably homogenous. It is conceivable that the lack of clear driver mutations may indicate that the key drivers are: 1) as in other cancers, including endocrine cancers, gene fusion events (splice-variants and translocations) which contribute the “second hit”; or that in ~40% of GCT, TERT mutations are an important tumorigenic event with perhaps loss of KMT2D in a small subset.
Our WES study [85] confirmed the report, from Pilsworth et al., of a telomerase gene (TERT) promoter mutation [92]. The TERT gene encodes the catalytic subunit of telomerase; TERT transcriptional regulation is the limiting step in telomerase activity. Elongation and/or preservation of telomere length is regarded as a hallmark of cancer. Two hot-spot mutations in the telomerase promoter, -124C > T and -146C > T are commonly found in specific cancers: melanoma, glioblastoma, bladder cancer and thyroid cancer, but not in common epithelial cancers, such as breast and prostate [87]. Our analysis using targeted PCR identified 11 of 26 (i.e., 42%) of the GCT in our analysis to be heterozygous for the -124C > T TERT promoter mutation - a frequency that matches the above cancers [87]. 29% of the stage 1 GCT were heterozygous for the mutation, while 67% of the stage 3 GCT contained the mutation [85]. The -124C > T mutation is also present in the aGCT-derived KGN cell line [85]. There are
Increased telomerase activity appears also to be associated with cell proliferation independent of telomere lengthening [94]. TERT has been reported to interact with major oncogenic signaling pathways including c-MYC, NFκB, and Wnt/β-catenin. Of these, activation of NFκB signaling has been reported in the KGN cell line [91, 95] and p65 nuclear localization has been reported in GCT [96], although previous studies [85, 86, 88, 90] have not identified mutations in these pathways.
It has been noted that melanoma, glioma, and papillary thyroid and bladder carcinomas, all of which have a high frequency of TERT promoter mutations, are characterized by activation through BRAF or EGFR mutation of the MAPK signaling pathway [97]. This association is intriguing given this high frequency of the TERT promoter mutation in GCT and the suggestion from pathway analysis of the WES study linking one of the canonical pathways to signaling through the EGFR family [85]. The high incidence of the TERT promoter mutation in GCT, together with the correlation of the presence of this mutation with stage, suggests that the presence of the TERT promoter mutation, as in other tumors, may be of prognostic and/or pathogenic significance, and acquired during tumor progression after the initial FOXL2 driver mutation.
DICER1 syndrome is a rare inherited disorder that increases the risk of a variety of cancerous and non-cancerous tumors that occur in the lungs, kidneys, ovaries and thyroid. DICER1 syndrome results from germ-line mutations in the
A pathogenic role for miRNA in SCST can be indicated by the identification of aberrant miRNA processing in SLCT and gynandroblastomas. However, studies of the ‘miRNA-ome’ have been limited. Rosario
Long non-coding (lnc) RNA’s have also been implicated in oncogenesis [101]. Evidence indicates that lncRNA can produce short peptides from small open reading frames (smORFs) which can regulate biological processes [102]. The status of both lncRNA, and indeed, smORFs remains to be investigated in SCST.
The human KGN and COV434 cell lines, have been thought to be derived from GCT, and are extensively used in studies of GCT as well as to model normal GC function. Both cell lines exhibit some features that are reminiscent of normal proliferating GC, including a functional FSH receptor and aromatase activity. Jamieson
Both KGN and COV434 cell lines are notable for constitutive activity of the NFκB and Braf/ERK signaling pathways [91, 95, 103]. A molecular study using a transcriptomic approach conducted by Rosario
The classification of COV434 as a GCT-derived cell line has been questioned. Recent studies show that this cell line was likely derived from a small-cell carcinoma of the ovary hypercalcemic-type (SCCOHT) [105, 106, 107]. The cell of origin of these tumors is unknown, with reports postulating they are likely derived from the germ cells [108]. Recent advances in molecular genetics have indicated that SCCOHT can be regarded as an ovarian malignant teratoid/rhabdoid tumor (MRT) [109]. SCCOHT are characterized by the loss of both SMARCA2 and SMARCA4, which are also not expressed in COV434 cells [105, 107]. Moreover, the lack of expression of RUNX2 and high expression of RUNX3 in COV434 suggests that these cells do not represent primary jGCT [106]. Noticeably, the study of Karnezis
A number of mouse models in which GCT arise have been reported, however none truly recapitulate the human disease [2, 110]. Liu
The uncommon nature of SCST limits the ability to develop targeted therapies and evaluate them in well-powered clinical trials. A recent search of clinicaltrials.gov showed only 11 trials that are either active of recruiting involving SCSTs, with only five completed results described. The application of new sequencing technologies may lead to the discovery of novel driver genes that lead to these rare ovarian cancers. However, as discussed above, these have so far been elusive from the limited studies performed to date.
Surgical treatment is the mainstay for peri-and postmenopausal women diagnosed with aGCT, with total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO) and full staging surgery thought to be the most appropriate initial treatment [124]. Randomized trials of adjuvant chemotherapy are not available, and for patients with poor prognosis, adjuvant platinum-based chemotherapy is generally considered either alone or in combination with doxorubicin and cyclophosphamide (CAP) [125, 126], vinblastine and bleomycin (PVB) [127], etoposide or etoposide and bleomycin (BEP) [128, 129]. The use of these treatment regimens is often based on those employed for epithelial ovarian cancer and in the main have proven to be of limited benefit [130].
Hormone treatment has shown promise in the treatment of advanced GCT based on their frequent estrogen dependence [2, 131, 132]. A systematic review of hormonal therapy for GCT revealed a pooled response rate of 71% and aromatase inhibitors (AI) were identified by far the most effective agents [131]. In a more recent study, the use of AI in 25 cases with known outcomes, the response rate to AIs was 48% (12/25) and the clinical benefit rate was 76% (19/25) [132]. Although these numbers are limited, they indicate the use of AIs as a potential alternative to chemotherapy, although the mechanisms involved in GCT sensitivity to AIs remains undefined. Other forms of hormone therapy have also previously shown promise with reports of prolonged remission (14–42 months) documented in patients with extensive disease treated with high doses of medroxyprogestroneacetate [133, 134].
The expression of vascular endothelial growth factor (VEGF) appears persistent with most GCT, with almost all tumors (93%) showing positive VEGF immunostaining in one study [135, 136]. The use of the anti-VEGF-A monoclonal antibody, bevacizumab, was shown to cause apoptosis in GCT-derived cells
Tyrosine kinases are well recognized as being fundamental to many growth factor signaling pathways in both normal and malignant cells. The advent of specific inhibitors of tyrosine kinases (TKI) has focused attention on the potential of TK as therapeutic targets. In view of the evidence of activation of cell signaling in GCT and a case report of a recurrent GCT responding to the TKI, imatinib (Gleevec), our group demonstrated that the GCT-derived cell lines were inhibited by imatinib and indeed by the newer more potent analog, nilotinib, but at concentrations higher than those required for the targeted receptor kinases [140]. The AP-1 signaling pathway is also constitutively activated in GCT [95]. We tested a TKI, sorafenib (Nexavar, Bayer), which has high affinity for Raf-1 and Braf, in addition to the above-mentioned TK, and found that this TKI elicits a dose dependent inhibition of both cellular proliferation and viability in both cell lines at concentrations equivalent to that seen in other systems [141]. A commercially available Raf-1 kinase inhibitor was also examined and found to have no effect on cell proliferation and viability in both cell lines, thus implicating Braf in the activated AP-1 signaling [141]. Based on these data, clinical investigation of sorafenib or possibly a more potent BRAF inhibitor, such as vemurafenib or dabrafenib, may be warranted.
Little is known about the immune response in SCST. Expression of the immune checkpoint protein, programmed death-ligand 1 (PD-L1) has been reported only in abstract form, and present in ~75% of SCSTs [142], however, immunotherapy has not been reported in a clinical trial for these tumors. A more recent study by Pierini et al., suggests that tumor infiltrating lymphocytes (TILS) are the main immune population in GCT [143], and that after
Based on several studies, there is also the potential for more targeted therapies that arise from identifying the molecular mechanisms that contribute to the pathogenesis of GCT. The NFκB signaling pathway is often involved in cancer development; activated NFκB increases the expression of genes involved in cell proliferation, metastasis, angiogenesis and anti-apoptosis [144]. Apoptosis is directed by activated caspases. The Inhibitors of Apoptosis (IAP) proteins suppress apoptosis through the inhibition of the caspases. The cellular IAP1 (cIAP1 or BIRC2), cellular IAP2 (cIAP2 or BIRC3) and X chromosome-linked IAP (XIAP or BIRC4) are the main IAPs with known roles in apoptosis and cancer [145, 146, 147]. XIAP is the best characterized and also the most potent caspase inhibitor, blocking both intrinsic and extrinsic apoptotic signals by directly inhibiting caspases-3, −7 and − 923. cIAP1 and cIAP2 have less potent roles in opposing these pathways as they do not directly bind caspases, however they can indirectly cause caspase cleavage [145, 146, 147]. Inhibition of cIAPs and XIAP causes cells to become more receptive to both intra- and extracellular apoptotic signals [148]. XIAP is predominantly regulated by an endogenous mitochondrial protein called second mitochondria-derived activator of caspases (Smac), which is released during apoptosis, and interacts with XIAP through conserved amino acid residues in the BIR3 domain of XIAP to antagonize XIAP-mediated caspase inhibition [149].
Due to its elevated expression and prominent ability to inhibit cell death, XIAP is an attractive therapeutic target for anti-cancer treatment [145, 146, 147]. Smac-mimetics (SM) bind directly to XIAP with high affinity to prevent caspase binding, thus neutralizing XIAPs pro-oncogenic function. A number of Smac-mimetics have demonstrated good anti-cancer activity in preclinical studies, and several have already passed primary phase clinical trials, suggesting that these compounds are well tolerated [146]. Though XIAP, IAP or pan-IAP inhibitors have shown some efficacy as single agents, the majority of studies have shown more promise when used in a rational drug combination strategy [146]. We have shown
Recent genetic discoveries have provided profound insights into the molecular pathogenesis of ovarian SCST. As with other uncommon tumor types, insight from research of SCST will potentially be prismatic; that is, it will help clarify molecular mechanisms involved in oncogenesis. In SLCT, the discovery of DICER1 mutations highlight both the complexity and asymmetry of miRNA processing, while also supporting the potential for ‘non-coding’ RNA in playing a critical role in malignant cancers. In the case of jGCT, the presence of the recurring mutations in the
This work is supported by grants-in-aid from the RIVKIN, US Department of Defense (OC170256), Australian Government Medical Research Future Fund (MRFF #1199749), Cancer Council Victoria; the Ovarian Cancer Research Foundation (S.C.); the Granulosa Cell Tumor of the Ovary Foundation; the National Health & Medical Research Council of Australia through a Project Grant (#1058334). The Hudson Institute is supported by the Victorian Government’s Operational Infrastructure Scheme.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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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. 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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. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. 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Her research interests include microalgal biotechnology with an emphasis on microalgae-based products.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",institutionURL:null,country:{name:"Brazil"}}}]},{type:"book",id:"7953",title:"Bioluminescence",subtitle:"Analytical Applications and Basic Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7953.jpg",slug:"bioluminescence-analytical-applications-and-basic-biology",publishedDate:"September 25th 2019",editedByType:"Edited by",bookSignature:"Hirobumi Suzuki",hash:"3a8efa00b71abea11bf01973dc589979",volumeInSeries:4,fullTitle:"Bioluminescence - Analytical Applications and Basic Biology",editors:[{id:"185746",title:"Dr.",name:"Hirobumi",middleName:null,surname:"Suzuki",slug:"hirobumi-suzuki",fullName:"Hirobumi Suzuki",profilePictureURL:"https://mts.intechopen.com/storage/users/185746/images/system/185746.png",biography:"Dr. Hirobumi Suzuki received his Ph.D. in 1997 from Tokyo Metropolitan University, Japan, where he studied firefly phylogeny and the evolution of mating systems. 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