Cyber-attack strategies.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"10899",leadTitle:null,fullTitle:"Postharvest Technology - Recent Advances, New Perspectives and Applications",title:"Postharvest Technology",subtitle:"Recent Advances, New Perspectives and Applications",reviewType:"peer-reviewed",abstract:"Postharvest management of food crops is an important part of food safety and security across the supply chain. It includes processing of agricultural produce, storage, packaging and coating, postharvest disease management, extending shelf life, and maintaining food quality and safety. Postharvest Technology - Recent Advances, New Perspectives and Applications discusses some important aspects of postharvest technologies. Chapters address such topics as postharvest preservation technology, postharvest disease management, and postharvest processing and packaging.",isbn:"978-1-83969-924-5",printIsbn:"978-1-83969-923-8",pdfIsbn:"978-1-83969-925-2",doi:"10.5772/intechopen.95208",price:119,priceEur:129,priceUsd:155,slug:"postharvest-technology-recent-advances-new-perspectives-and-applications",numberOfPages:268,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"ce6f836b93e9e456c0f87a46deca8937",bookSignature:"Md Ahiduzzaman",publishedDate:"April 28th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10899.jpg",numberOfDownloads:1567,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:3,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 14th 2021",dateEndSecondStepPublish:"June 11th 2021",dateEndThirdStepPublish:"August 10th 2021",dateEndFourthStepPublish:"October 29th 2021",dateEndFifthStepPublish:"December 28th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"321606",title:"Dr.",name:"Md",middleName:null,surname:"Ahiduzzaman",slug:"md-ahiduzzaman",fullName:"Md Ahiduzzaman",profilePictureURL:"https://mts.intechopen.com/storage/users/321606/images/system/321606.jpg",biography:"Professor Md. Ahiduzzaman, Ph.D., obtained a bachelor’s degree in Agricultural Engineering from Bangladesh Agricultural University in 1993, an MSc in Energy Systems and Management from University of Flensburg, Germany, in 2006, and a Ph.D. in Mechanical Engineering from Islamic University of Technology, Bangladesh, in 2011. He completed his postdoctoral studies at the University of Alberta, Canada. He was awarded a DAAD Scholarship (Germany) and NSERC Postdoctoral Fellowship (Canada). Dr. Ahiduzzaman has been researching and teaching in the field of agricultural engineering, focusing on the processing of field crops, the processing technology of fruits and vegetables, drying technology, renewable energy, and framework development for greenhouse gas mitigation policies in agriculture and other sectors. He has experience working in multi-organizational and interdisciplinary teams, evaluating research, and developing projects in the agricultural engineering sector. He has more than sixty publications in scientific journals and several books and book chapters to his credit. He has had a distinguished academic and research career for more than twenty-four years.",institutionString:"Bangabandhu Sheikh Mujibur Rahman Agricultural University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Bangabandhu Sheikh Mujibur Rahman Agricultural University",institutionURL:null,country:{name:"Bangladesh"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"26",title:"Agricultural Engineering",slug:"agricultural-and-biological-sciences-agricultural-engineering"}],chapters:[{id:"79624",title:"Challenges and Measures to Recapitalise Handling of Postharvest Crops in Developing Countries",doi:"10.5772/intechopen.101222",slug:"challenges-and-measures-to-recapitalise-handling-of-postharvest-crops-in-developing-countries",totalDownloads:48,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Global population growth and environmental burdens have caused rising concerns regarding future food security. Contradictorily, many crops are discarded at postharvest stages without being consumed. Postharvest loss in developing countries is mainly attributable to a lack of capital and technology for food storage, processing (i.e. threshing, drying and packaging) and distribution. This study endeavours to investigate the causes and the potential measurements of postharvest losses in developing countries. Specifically, limited budgets in developing countries cannot finance the cost of capital investment; therefore, reliance on third parties such as international organisations is considered a realistic measurement. This investigation establishes that in some cases, a lack of knowledge and skills can result in a lack of full utilisation of the capital provided for handling post-harvest crops. Supporters are discouraged from providing development assistance in circumstances in which whether sufficient results will be achieved is unclear. This study emphasises that enabling the successful long-term utilisation of capital for postharvest handling is critical to improving the rate of vital crop loss.",signatures:"Ryusuke Oishi",downloadPdfUrl:"/chapter/pdf-download/79624",previewPdfUrl:"/chapter/pdf-preview/79624",authors:[{id:"193889",title:"Dr.",name:"Ryusuke",surname:"Oishi",slug:"ryusuke-oishi",fullName:"Ryusuke Oishi"}],corrections:null},{id:"80462",title:"Postharvest Preservation Technology of Cereals and Legumes",doi:"10.5772/intechopen.102739",slug:"postharvest-preservation-technology-of-cereals-and-legumes",totalDownloads:64,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Cereals and legumes are prone to perishability and have very short shelf-life if not given proper treatment. During different handling and marketing operations, there is a huge postharvest loss of agricultural produce. The qualitative and quantitative losses incurred in cereals and legumes commodities between harvest and consumption are huge. Qualitative losses such as loss inedibility, nutritional quality, calorific value, and consumer acceptability of fresh produce are much more difficult to assess than are quantitative losses. The major cause of postharvest loss (PHL) is the availability of poor infrastructure for postharvest technology (PHT) and processing of commodities. These losses can only be minimized by proper handling, marketing, and processing of the agricultural commodities; as well as the use of modern preservation technologies such as irradiation, radio frequency heating, etc. The sufficient knowledge of pre-and post-harvest preservation technologies and the provision of adequate and sufficient storage facilities for cereals and legumes handling and distribution would help to mitigate the incidence of postharvest deterioration and therefore improve the availability of cereals and legumes in the market and subsequent reduction in malnutrition for increased food security. Postharvest preservation technology of cereals and legumes is very fundamental in reducing postharvest losses and increasing food security.",signatures:"Theophilus M. Ikegwu, Clement C. Ezegbe, Chioke A. Okolo and Chigozie E. Ofoedu",downloadPdfUrl:"/chapter/pdf-download/80462",previewPdfUrl:"/chapter/pdf-preview/80462",authors:[{id:"419858",title:"Dr.",name:"Theophilus M.",surname:"Ikegwu",slug:"theophilus-m.-ikegwu",fullName:"Theophilus M. Ikegwu"},{id:"420119",title:"Mr.",name:"Clement C.",surname:"Ezegbe",slug:"clement-c.-ezegbe",fullName:"Clement C. Ezegbe"},{id:"420120",title:"Mr.",name:"Chioke A.",surname:"Okolo",slug:"chioke-a.-okolo",fullName:"Chioke A. Okolo"},{id:"447080",title:"Mr.",name:"Chigozie E.",surname:"Ofoedu",slug:"chigozie-e.-ofoedu",fullName:"Chigozie E. Ofoedu"}],corrections:null},{id:"79822",title:"Stored Grain Pests and Current Advances for Their Management",doi:"10.5772/intechopen.101503",slug:"stored-grain-pests-and-current-advances-for-their-management",totalDownloads:295,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"During the offseason, when fresh food is not available, humans have to consume stored grain food. Unfortunately, these stored grains are later infested with many pests. Foods stored in bags and bins are very much susceptible to infestation with several pests which can cause extensive post-harvest losses, spoilage, and less demand in markets, causing a huge economic crisis. Hence, successful management of stored grain pests becomes necessary to prevent these from insect pests. Current approaches for their management are one of the promising goals, as it includes preventive practices, monitoring, sanitation, and identification of main pathogens. Different management strategies of all the common stored grain pests viz. grain weevils, grain borers, grain moths, flour moths, mealworms, grain and flour beetles, booklice, mites, and parasites are enlisted here.",signatures:"Rayees Ahmad, Shafiya Hassan, Showkat Ahmad, Syed Nighat, Yendrambamb K. Devi, Kounser Javeed, Salma Usmani, Mohammad Javed Ansari, Sait Erturk, Mustafa Alkan and Barkat Hussain",downloadPdfUrl:"/chapter/pdf-download/79822",previewPdfUrl:"/chapter/pdf-preview/79822",authors:[{id:"319667",title:"Dr.",name:"Barkat",surname:"Hussain",slug:"barkat-hussain",fullName:"Barkat Hussain"},{id:"444975",title:"Dr.",name:"Rayees",surname:"Ahmad",slug:"rayees-ahmad",fullName:"Rayees Ahmad"},{id:"444976",title:"Dr.",name:"Shafiya",surname:"Hassan",slug:"shafiya-hassan",fullName:"Shafiya Hassan"},{id:"444977",title:"Dr.",name:"Showkat",surname:"Ahmad",slug:"showkat-ahmad",fullName:"Showkat Ahmad"},{id:"444978",title:"Dr.",name:"Syed",surname:"Nighat",slug:"syed-nighat",fullName:"Syed Nighat"},{id:"444979",title:"Dr.",name:"Yendrambamb",surname:"K. Devi",slug:"yendrambamb-k.-devi",fullName:"Yendrambamb K. Devi"},{id:"444980",title:"Dr.",name:"Kounser",surname:"Javeed",slug:"kounser-javeed",fullName:"Kounser Javeed"},{id:"444981",title:"Dr.",name:"Salma",surname:"Usmani",slug:"salma-usmani",fullName:"Salma Usmani"},{id:"444982",title:"Dr.",name:"Mohd Javid",surname:"Ansari",slug:"mohd-javid-ansari",fullName:"Mohd Javid Ansari"},{id:"444983",title:"Dr.",name:"Sait",surname:"Erturk",slug:"sait-erturk",fullName:"Sait Erturk"},{id:"444984",title:"Dr.",name:"Mustafa",surname:"Alkan",slug:"mustafa-alkan",fullName:"Mustafa Alkan"}],corrections:null},{id:"79678",title:"Robotic Heat Treatments for Mango and Prickly Pear Increase Shelf Life and Reduce Pathogen Infection",doi:"10.5772/intechopen.101570",slug:"robotic-heat-treatments-for-mango-and-prickly-pear-increase-shelf-life-and-reduce-pathogen-infection",totalDownloads:146,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Mexico is the main exporter of mango fruits and prickly pears, so new postharvest techniques to increase shelf life are studied. Thermal treatments on both fruits can affect their cuticle so it was reviewed. When mango latex remains within the fruits, it avoids sap burn and decreases anthracnose and stem end rot infestation, so two systems were developed to minimize latex de-sapping. A gripper cuts stems 0.5 cm long and cauterizes them with a hot knife implement. A heating gun applied paraffin wax to mangoes without the stem end and protected them better against anthracnose lesions. Physicochemical analysis of several mango varieties was carried out after harvesting, at market place and after pedicel cutting and cauterizing. Keitt mangoes showed the lower quantity of total soluble solids (TSSs) and total acidity (TA). When the pedicel was cauterized, TSS dropped. Two grippers were developed to cryo-cauterize prickly pears as this system is more energy-efficient than hot cauterization. A six-finger gripper moved over a pneumatic actuator toward a dry ice chamber to optimize pear cryo-cauterization. Gripper’s strong grasping damaged the fruits due to excessive compression. TSS and TA of cryo-cauterized fruit remained constant during the three months of fruit storage.",signatures:"Federico Félix Hahn Schlam",downloadPdfUrl:"/chapter/pdf-download/79678",previewPdfUrl:"/chapter/pdf-preview/79678",authors:[{id:"203571",title:"Dr.",name:"Federico",surname:"Félix Hahn Schlam",slug:"federico-felix-hahn-schlam",fullName:"Federico Félix Hahn Schlam"}],corrections:null},{id:"79995",title:"Postharvest Diseases of Vegetable Crops and Their Management",doi:"10.5772/intechopen.101852",slug:"postharvest-diseases-of-vegetable-crops-and-their-management",totalDownloads:188,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Vegetable crops have an important role in food and nutrition and maintain the health of soil. India is the second-largest producer of vegetables in the world with a 16% (191.77 MT) share of global vegetable production. Every year, diseases cause postharvest losses (40–60%) in vegetable crops due to their perishable nature under field (15–20%), packaging and storage (15–20%), and transport (30–40%). Profiling, detection, and diagnosis of postharvest vegetable pathogens (diseases) are essential for better understanding of pathogen and formulation of safe management of postharvest spoilage of vegetables. The vegetable produce is spoiled by postharvest pathogens and makes them unfit for human consumption and market due to the production of mycotoxins and other potential human health risks. Genera of fungal pathogens viz. Alternaria, Aschochyta, Colletotrichum, Didymella, Phoma, Phytophthora, Pythium, Rhizoctonia, Sclerotinia, Sclerotium, and bacterial pathogens viz. Erwinia spp., Pseudomonas spp., Ralstonia solanacearum, Xanthomonas euvesictoria were recorded as postharvest pathogens on vegetable crops. Fruit rot incidence of several post-harvest pathogens viz. Alternaria solani (30%), Phytophthora infestans (15%), Rhophitulus solani (30%), Sclerotium rolfsii (30%) fruit rot and X. euvesictoria (5%) canker on tomato; Colletotrichum dematium fruit rot (20%) on chili; Phomopsis vexans (60%) fruit rot on brinjal was recorded. Didymella black rot and Colletotrichum anthracnose were recorded on fruits of bottle gourd, pumpkin, ash gourd, and watermelon. Important leguminous vegetable crops are infected by postharvest pathogens viz. Ascochyta pisi, Colletotrichum lindemuthianum (Anthracnose), Sclerotinia sclerotiorum (white rot) and Pseudomonas syringae pv. phaseolicola (blight), Sclerotinia white rot, Alternaria blight. However, Xanthomonas black rot (10%) on cabbage and Pectinovora (Erwinia) soft rot (19%) were recorded as emerging post-harvest pathogens on cauliflower.",signatures:"Atma Nand Tripathi, Shailesh Kumar Tiwari and Tushar Kanti Behera",downloadPdfUrl:"/chapter/pdf-download/79995",previewPdfUrl:"/chapter/pdf-preview/79995",authors:[{id:"420639",title:"Dr.",name:"Atma Nand",surname:"Tripathi",slug:"atma-nand-tripathi",fullName:"Atma Nand Tripathi"}],corrections:null},{id:"78723",title:"Advances in Postharvest Disinfestation of Fruits and Vegetables Using Hot Water Treatment Technology-Updates from Africa",doi:"10.5772/intechopen.100351",slug:"advances-in-postharvest-disinfestation-of-fruits-and-vegetables-using-hot-water-treatment-technology",totalDownloads:157,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Hot Water Treatment (HWT) provides adequate phytosanitary assurance that treated fruits and vegetables exported abroad are free from devastating quarantine pests. Two systems for HWT are currently available for commercial use namely the batch/jacuzzi and the continuous flow system depending on user requirements. Several protocols have been developed the world over and a few in Africa, but adoption has been lagging because of various factors chief among them lack of large scale validations of experiments to guide application at the commercial level. Mango, Bell pepper, avocado, and French beans play an important role in the livelihoods of people in Africa. However, their export is constrained by pests such as the invasive Oriental fruit fly, the false codling moth, and thrips. To circumvent this issue, disinfestation HWT protocols have been developed which seek to provide quarantine assurance to lucrative export markets. Hot Water Treatment technology has several advantages over other conventional phytosanitary treatments. It provides a triple function of cleaning, disinfesting, and disinfecting and is friendly to users, consumers of the treated commodities, and the environment. We discuss HWT in the context of its future and applicability in Africa. It is the future of postharvest treatments.",signatures:"Shepard Ndlela, Nelson L. Mwando and Samira A. Mohamed",downloadPdfUrl:"/chapter/pdf-download/78723",previewPdfUrl:"/chapter/pdf-preview/78723",authors:[{id:"53233",title:"Dr.",name:"Samira A.",surname:"Mohamed",slug:"samira-a.-mohamed",fullName:"Samira A. Mohamed"},{id:"422290",title:"Dr.",name:"Shepard",surname:"Ndlela",slug:"shepard-ndlela",fullName:"Shepard Ndlela"},{id:"429463",title:"Mr.",name:"Nelson L.",surname:"Mwando",slug:"nelson-l.-mwando",fullName:"Nelson L. Mwando"}],corrections:null},{id:"79725",title:"Advances in Postharvest Packaging Systems of Fruits and Vegetable",doi:"10.5772/intechopen.101124",slug:"advances-in-postharvest-packaging-systems-of-fruits-and-vegetable",totalDownloads:145,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The production of vegetables and fruits is at a high rate but the major challenging task is the postharvest handling and processing of the products. Approximately 20–30% of the production is being wasted due to a lack of proper postharvest management. Many developments were made to reduce this wastage such as cold chain development, different storage structures, some drying methodologies to promote the shelf life of produce. But all these systems need to be improved and utilized commercially. The losses still occur due to a lack of sound knowledge on the chemical nature of products and different management techniques (e.g., drying, cooling, blanching). Therefore, the successful design of the cooling, packing, storage transport, and drying processes of fresh food requires linking materials sciences, fluid dynamics, mechanical deformation, food chemistry, and process control.",signatures:"Trina Adhikary and Durga Hemanth Kumar",downloadPdfUrl:"/chapter/pdf-download/79725",previewPdfUrl:"/chapter/pdf-preview/79725",authors:[{id:"422875",title:"Assistant Prof.",name:"TRINA",surname:"ADHIKARY",slug:"trina-adhikary",fullName:"TRINA ADHIKARY"},{id:"426729",title:"Mr.",name:"Ch. Durga Hemanth",surname:"Kumar",slug:"ch.-durga-hemanth-kumar",fullName:"Ch. Durga Hemanth Kumar"}],corrections:null},{id:"80247",title:"Postharvest Technology of Tamarind",doi:"10.5772/intechopen.101096",slug:"postharvest-technology-of-tamarind",totalDownloads:104,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tamarind is a multi-purpose long-lived tree with heavy drooping branches and thick foliage. The entire fruit consists of 55% pulp, 34% seeds, and 11% hull and fibers. The tamarind tree produces numerous elongated fruit pods in a season that encompasses its branches in myriad. Brittleness in shell, changes in testa color, and a hollow sound from fruit when finger pressed signify matured fruit of the tree. Postharvest operations involved in Tamarind are drying, dehulling, defining, deseeding, pressing into cake, and storage. These operations are carried out by traditional and mechanical methods. Tamarind dehullers and deseeder were developed with efficiencies of around 94% and 83% respectively to minimize the losses involved in manual handling. The intrinsic value of raw tamarind may be furthermore desirable through processing into value-added products.",signatures:"P. Sudha, P. Rajkumar, A. Astina Joice, I.P. Sudagar and R. Arulmari",downloadPdfUrl:"/chapter/pdf-download/80247",previewPdfUrl:"/chapter/pdf-preview/80247",authors:[{id:"420982",title:"Dr.",name:"P.",surname:"Sudha",slug:"p.-sudha",fullName:"P. Sudha"},{id:"441227",title:"Dr.",name:"P.",surname:"Rajkumar",slug:"p.-rajkumar",fullName:"P. Rajkumar"},{id:"441228",title:"Dr.",name:"A.",surname:"Astina Joice",slug:"a.-astina-joice",fullName:"A. Astina Joice"},{id:"441229",title:"Dr.",name:"I.P.",surname:"Sudagar",slug:"i.p.-sudagar",fullName:"I.P. Sudagar"},{id:"441230",title:"Dr.",name:"R.",surname:"Arulmaru",slug:"r.-arulmaru",fullName:"R. Arulmaru"}],corrections:null},{id:"80454",title:"Processing of Tree Nuts",doi:"10.5772/intechopen.102623",slug:"processing-of-tree-nuts",totalDownloads:86,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tree nuts are consumed as healthy snacks worldwide and are important economic crops. In this chapter, post-harvest processing technologies of tree nuts are discussed, with focus on the drying, disinfection, disinfestation, and downstream processing technologies (blanching, kernel peeling and roasting) for the control and preservation of product quality and safety. Almonds, walnuts, and pistachios are selected as the representative crops for the discussion. Current status, recent advances, and challenges in the scientific research, as well as in the industrial productions are summarized. Some new perspectives and applications of tree nut processing waste and byproducts (such as shells and hulls) are also introduced. The contents presented in this chapter will help both scientists and stakeholders to better understand the tree nut processing and provide technological recommendations to improve the throughput, efficiency, and sustainability of the processes, and preserve the quality and safety of the products.",signatures:"Chang Chen and Zhongli Pan",downloadPdfUrl:"/chapter/pdf-download/80454",previewPdfUrl:"/chapter/pdf-preview/80454",authors:[{id:"422690",title:"Dr.",name:"Chang",surname:"Chen",slug:"chang-chen",fullName:"Chang Chen"},{id:"422904",title:"Prof.",name:"Zhongli",surname:"Pan",slug:"zhongli-pan",fullName:"Zhongli Pan"}],corrections:null},{id:"79752",title:"Edible Coating",doi:"10.5772/intechopen.101283",slug:"edible-coating",totalDownloads:230,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Postharvest losses are rampant due to lack of proper storage conditions and handling of the fresh food products. The perishable nature of fruits and vegetables makes their shelf life limited due to some extrinsic factors such as some environmental conditions and preservation conditions as well as some intrinsic factors such as respiration rate, ethylene production and transpiration. Among the other postharvest technologies available, edible coatings seems to be one novel method which has been verified to have a positive and safe approach to extending the shelf life of products. This type of packaging is made from various natural resources like polysaccharide, protein and lipid materials. Edible packaging materials can be divided into two main groups including edible coatings and edible films. It has so many benefits such as serving as a moisture barrier, oxygen scavenger, ethylene scavenger, antimicrobial properties among others. Different methods of application of the edible coating on the food materials include; dipping, spraying, brushing, layer by layer among others. There have been several verifications of the positive impact of edible coatings/films on pome fruits, Citrus fruits, Stone fruits, tropical and exotic fruits, berries, melon, tomatoes and others.",signatures:"Kofi Owusu-Akyaw Oduro",downloadPdfUrl:"/chapter/pdf-download/79752",previewPdfUrl:"/chapter/pdf-preview/79752",authors:[{id:"421005",title:"B.Sc.",name:"Kofi",surname:"Owusu-Akyaw Oduro",slug:"kofi-owusu-akyaw-oduro",fullName:"Kofi Owusu-Akyaw Oduro"}],corrections:null},{id:"79451",title:"Postharvest Processing, Value Addition and Marketing of Mushrooms",doi:"10.5772/intechopen.101168",slug:"postharvest-processing-value-addition-and-marketing-of-mushrooms",totalDownloads:111,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Mushrooms are macrofungi having a higher content of water (80–90%) and multinutrients. The presence of various phytochemicals, enzymes, primary metabolites and secondary mycometabolites results in poor shelf-life, quick deterioration, and huge postharvest losses (30–35%). Fresh mushrooms are short lived (1–8 days). Value chain management is thus necessary from the production to its harvest to meet the food and nutritional requirements. Every effort was made to extend the shelf-life of mushrooms for either short period or long period of storage. Washing or pretreatment, packaging, transport and marketing were some of the important standardized techniques for short-term storage of mushroom. On the other hand, drying, pickling and steeping preservation methods were some other techniques to extend the shelf-life of mushroom for a longer period of time during storage. Value addition of mushroom enhanced the quality and addressed the demand for ready-made or ready-to-make food products. Fresh/dry oyster mushroom in various proportions (5–10%) was used to prepare mushroom paratha, mushroom suji, mushroom sandwich, mushroom chakli, mushroom seb, mushroom-based biofortified wheat flour, mushroom-based papad, nuggets, mushroom bijoura, biscuits, etc. Several mushroom-based, value-added products like Royal Oyster Capsules were prepared by Self Help Groups women at Kapadah (Kabirdham).",signatures:"Mahesh Prasad Thakur, Harvinder K. 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Nanofibers are fabricated by different techniques such as electrospinning, self-assembly, template-assisted synthesis, and thermal-induced phase separation. They have different physical and chemical properties with potential applications in various fields. The recent applications of nanofibers have greatly influenced many fields, including material science, engineering, chemistry, environmental, and medical sciences.
\r\n\r\n\t
\r\n\tThis book aims to present an overview of the current status of nanofibers, fabrication and recent trends in the fabrication of nanofibers, and functional nanofibers and applications of nanofibers in various fields including environmental, bio-sensing, drug delivery, catalysis, and medical. The book hopes to provide a piece of up-to-date information about the mentioned topics and fundamental knowledge necessary for the advanced study in the field of nanofibers and their applications, making it interesting to research students, scientists, engineers, and material scientists.
Cyber-physical systems (CPS) are the integration of the cyber-world of computing and communications with the physical world. In many systems, control of a physical plant is integrated with a wireless communication network, for example, transportation networks, electric power networks, integrated biological systems, industrial automation systems, and economic systems [1, 2]. Since CPSs use open computation and communication platform architectures, they are vulnerable to suffering adversarial physical faults or cyber-attacks. Faults and cyber-attacks are referred to as
Recent real-world cyber-attacks, including multiple power blackouts in Brazil [3], and the Stuxnet attack [4] in 2010, showed the importance of providing security to CPSs. Identification and modeling process as [5, 6] which are based on data can be seriously affected by corrupted data. As a result, information security techniques [7] may be not sufficient for protecting systems from sophisticated cyber-attacks. It is suggested in [8] that information security mechanisms have to be complemented by specially designed resilient control systems. Controlling CPS with sensors and actuators, who are hijacked/corrupted remotely or physically by the attackers, is a challenge. The use of novel control/observation algorithms is proposed in this chapter for recovering CPS performance online if an attacker penetrates the information security mechanisms.
\nCyber security of CPS must provide three main security goals:
In [17], new adaptive control architectures that can foil malicious sensor and actuator attacks are developed without reconstructing the attacks, by means of feedback control only. A sparse recovery algorithm is applied to reconstruct online the cyber-attacks in [18]. Sliding mode control with advantages of quick response and strong robustness is one of the best approaches to control CPS [19, 20, 21, 22]. In [23], a finite-time convergent higher-order sliding mode (HOSM) observer, based on a HOSM differentiator and a sparse recovery algorithm, are used to reconstruct online the cyber-attack in a nonlinear system. Detection and observation of a scalar attack by a sliding mode observer (SMO) has been accomplished for a linearized differential-algebraic model of an electric power network when plant and sensor attacks do not occur simultaneously [24]. Cyber-attacks against phasor measurement unit (PMU) networks are considered in [25], where a risk mitigation technique determines whether a certain PMU should be kept connected to network or removed. In [26] a sliding mode-based observation algorithm is used to reconstruct the attacks asymptotically. This reconstruction is approximate only, since pseudo-inverse techniques are used.
\nIn this chapter, CPSs controlled by a control input subject to sensor attacks and state/plant attacks are considered. The corrupted measurements propagate the attack signals to the CPS through the control signals causing CPS performance degradation. The main challenge that is addressed in the chapter is online exact reconstruction of the sensor and state attacks with an application to an electric power network. The contribution of this chapter is:
Novel fixed and adaptive-gain SMO for the linearized/linear CPS under attack are proposed for the online reconstruction of sensor attacks. The
A super twisting SMO is applied to reconstruct the state/plant time-varying attacks of the linearized/linear CPS under attack.
For online state/plant attack reconstruction in
An algorithm that use sliding mode differentiation techniques [29] in concert with the finite-time convergent observer for the sparse signal recovery is applied to online reconstruction of time-varying attack in nonlinear CPS under attack when we have limited measurements and more possible sources of attack [30].
In a real-world power network, only a small group of generator rotor angles and rates is directly measured, and typical attacks aim at injecting disturbance signals that mainly affect the sensorless generators [24].
\nThe small-signal version of the classic structure-preserving power network model is adopted to describe the dynamics of a power network. Consider a connected power network consisting of \n
The CPS that motivates the results presented in this work is the US Western Electricity Coordinating Council (WECC) power system [8] under attack with three generators and six buses, whose electrical schematic is presented in Figure 1. The mathematical model of the power network in Figure 1 under sensor stealth attack and deception attack can be represented as the following descriptor equations that consist of differential and algebraic equations [8]:
\nThe WECC power system [
where the state vector \n
The measurement corruption attacks through an output control feedback. The matrices \n
The inputs \n
Note that \n
The system (1) was simulated with and without above attacks. Based on the simulation results shown in Figures 2 and 3, the stealth attack in (4) yields inappropriate degradation of the power network performance.
\nComparing corrupted sensor measurements (
Comparing corrupted states (
This motivates why online reconstruction of the attacks followed by cleanup of the measurements prior to using them in control signal is of prime importance for retaining the performance of the power network (as it will be shown in Section VI where the proposed SMO is applied to achieve this goal). The case study of the power network (1) will be further discussed in details in Section 6.
\nConsider the following completely observable and asymptotically stable system
\nwhere \n
where \n
The attack/fault vector is partitioned accordingly as
\nTherefore, Eq. (5) can be rewritten as
\nwhere \n
Attack plan | \n\n\n | \n\n\n | \nAccess to all sensors | \nNeed to know the system model | \n
---|---|---|---|---|
Stealth attack | \n\n | √ | \n\n | \n |
Deception attack | \n√ | \n\n | \n | \n |
Reply attack | \n√ | \n√ | \n√ | \n\n |
Covert attack | \n√ | \n√ | \n\n | √ | \n
False data injection attack | \n\n | √ | \n\n | √ | \n
Cyber-attack strategies.
Since \n
selected so that
\nTaking into account (10), system (8) is reduced to
\nwhere \n
The problem is to protect the closed loop system (11) from the sensor attack \n
as time increases and.
\n(b) “cleanup” of the plant and sensors so that the dynamics of the CPS under attack (11) approaches,
\nas time increases, to.
\nNote that Eq. (13) represents the compensated CPS that converges to CPS without attack as time increases.
\nIn this chapter, for the
Consider the linearized system in Eq. (5) with \n
Considering system Eq. (14) and assuming assumption (A1) holds, then as show in [29] there exists a matrix \n
is nonsingular and the change of coordinates \n
After the linear changing of coordinate, the CPS Eq. (14) is rewritten as
\nwith \n
Defining a further change of coordinates \n
where \n
\n\n
Since \n
where \n
Scale state component \n
where \n
where \n
A SMO is proposed to reconstruct the attack in order to clean up the measurements and states and to allow the use of clean measurement in the control signal.
\nDefine a (sliding mode) observer for the system Eq. (22) as
\nwhere \n
are the gain matrices where \n
where scalar gain \n
Defining \n
and by direct substitution from Eqs. (22) and (23) that
\nThe idea is to force a sliding motion on
\nThe first main results, based on the SMO with the fixed-gain injection term, is formulated in the following theorem.
\nThen, as soon as the sliding mode is established in finite time in Eq. (27) on the sliding surface Eq. (28) by means of the injection term Eq. (25) with \n
where \n
Proof of the Theorem 1 is omitted for brevity.
\nIn Eq. (29), it was assumed that the perturbation term \n
The constant gain \n
A sufficient condition to ensure sliding on \n
An error signal is defined as
\nwhere the scalars \n
where the time-varying scalar \n
where \n
where \n
and assume that \n
for any given \n
Proof of Theorem 2 is based on the results in [32] and is omitted for brevity.
\nConsider the completely observable linearized system Eq. (11) with \n
where \n
The system Eq. (40) is assumed to have an input-output vector relative degree \n
Without loss of generality, it is assumed that \n
where integers \n
The following SMO [33] is used to estimate the states of system Eq. (40):
\nwhere the matrices of appropriate dimensions \n
where \n
The definition of the symmetric positive definite matrix \n
where the constituent signals in Eq. (45) are given from the continuous second-order sliding mode observer as
\nfor \n
The scalar function \n
and the continuous injection term \n
Proof: Defining the state estimation error as \n
then it follows that
\nBy choosing suitable gains \n
for all \n
Since \n
as \n
where \n
According to (A1), \n
Consider the locally stable system Eq. (11) where \n
The system given by Eq. (11) with the involutive distribution \n
where \n
With an involutive distribution \n
If assumption (A9) is satisfied, then it is always possible to find \n
is a local diffeomorphism in a neighborhood of any point \n
In order to estimate the derivatives \n
\n\n
for \n
Therefore, the following exact estimates are available in finite time:
\nNext, integrate Eq. (60) with \n
and with some initial condition from the stability domain of the internal dynamics, a asymptotic estimate \n
Therefore, the asymptotic estimate for the mapping (63) is identified as
\nasymptotic estimate \n
Since the finite-time exact estimates \n
where \n
Considering Eq. (11) and \n
In some applications, there are a limited number of measurements, \n
Notice that a more general format of (5) is considered here where matrix \n
The problem of recovering an unknown input signal from measurements is well known, as a left invertibility problem, as seen in several works [30, 37], but this problem was only treated in the case where the number of measurements is equal or greater than the number of unknown inputs. The left invertibility problem in the case of fewer measurements than unknown inputs has no solution or more exactly has an infinity of solutions.
\nIn particular, the objective of exact recovery under sparse assumptions denoted for the sake of simplicity as “sparse recovery” (SR) is to find a concise representation of a signal using a few atoms from some specified (over-complete) dictionary,
\nwhere \n
for any \n
where \n
The problem of SR is often cast as an optimization problem that minimizes a cost function constructed by leveraging the observation error term and the sparsity inducing term [37], i.e.,
\nIn Eq. (77) the original sparsity term is the quasi norm \n
Under the sparse assumption of \n
where \n
where \n
Under Definition 1, the state \n
The measured output under attack \n
The filter output \n
where \n
If assumption (A2), (A7), and (A9) hold for system Eq. (81), i.e., the relative degree vector of Eq. (81) is \n
for \n
Then, the following algebraic equation is found from Eq. (84):
\nwhere \n
Finally, filtered system Eq. (5), as it is rewritten in Eq. (85), is in the same form of Eq. (74). Then, sparse recovery algorithm discussed in Section 5.4.1 is applied to Eq. (85) to reconstruct \n
Consider the mathematical models (1)–(4) of the US Western Electricity Coordinating Council (WECC) power system [8] with three generators and six buses (Figure 1) when the sensors of the generator speed deviations from synchronicity are under stealth attack and plant is under deception attack.
\nIf (A12) holds, then the variable \n
Substituting (87) into (1), then it follows that
\n\n
The three sensors of rotor angles, \n
The \n
In the first step of attack reconstruction, \n
where \n
There are six sources \n
Deception attacks \n
Plant attack
Plant attack
Plant attack
Sensor attack
(a) Corrupted output
The critical infrastructures like power grid, water resources, etc. are large interconnected cyber-physical systems whose reliable operation depends critically on their cyber substructure. In this chapter, cyber-physical systems when their sensors and/or states are under attack or experiencing faults are investigated. The sensor and states/plant attacks are reconstructed online by using a fixed-gain and adaptive-gain sliding mode observers. As soon as the attacks are reconstructed, corrupted measurements and states are cleaned from attacks, and the control signal that uses cleaned measurements provides cyber-physical system performance close to the one without attack. The effectiveness of the proposed approach is shown by simulation results of a real electrical power network with sensors under stealth attack and states under deception attacks.
\nThe concept of using radiolabeled receptor-binding peptides and proteins to target receptor-(over)expressing tissues
Besides stability toward enzymes, lipophilicity is very important. The preferred route of clearance of a peptide-based radiopharmaceutical is via the kidneys. For targeting of tumors, cardiovascular diseases, and infections or inflammation, the lipophilicity of the compound should not be too high (log P < 1) as lipophilic compounds result in non-specific binding and slower blood clearance via mainly the hepatobiliary route. In contrast, molecular imaging tracers that target brain diseases such as Alzheimer require a higher lipophilicity (log P > 1) in order to cross the blood–brain barrier (BBB). Lipophilicity of molecular imaging tracers can be reduced by linking them to polyethylene glycol (PEG) chains, a technique called PEGylation. An alternative method to reduce lipophilicity of a tracer is attachment of carbohydrates, as this enhances the hydrophilicity, resulting in reduced hepatobiliary uptake, enhanced urinary excretion, and reduced nonspecific binding [4].
Furthermore, conjugation of chelators like DOTA (1,4,7,10-tetraazacyclododecane-tetraacetic acid), NOTA (1,4,7-triazacyclononane-triacetic acid), or DTPA (diethylenetriaminepentaacetic acid) also reduce the lipophilicity of an imaging agent. However, modification of a tracer by for example PEGylation, glycosylation or conjugation to a chelator, can also affect the affinity of a peptide for the receptor and thus the effectiveness of the radiotracer.
A chelating agent will not only influence the hydrophilicity of a peptide or protein, but it will also increase the overall size of the radiotracer and thus the pharmacokinetics. To preserve biological activity and receptor-binding affinity, conjugation of a chelator must be performed at a site remote from the active and receptor-binding region of the tracer [5]. Total chemical protein synthesis enables single site-specific protein modification, which cannot be achieved through regular labeling methods of biologically obtained proteins. To prevent interference of the chelator with the active and receptor-binding region of the peptide, introduction of a linker may be necessary. These linkers (PEG chains, amino acids, aliphatic hydrocarbon chains, etc.) can be used as pharmacokinetic modifiers (PKMs) to adjust the pharmacokinetics of the probe.
Several acyclic and cyclic bifunctional chelators have been developed for both diagnostic and therapeutic applications (Figure 1). A bifunctional chelator is a molecule which can be covalently coupled to the targeting compound and has the ability to chelate a (radio)metal. The most widely used chelators are DTPA, DOTA, and NOTA or derivatives thereof. A chelator should effectively sequester the radionuclide in high-yields (quantitative) and with high stability. Unstable complexation of the radionuclide by the chelator can lead to trans-chelation of the radionuclide to blood proteins and enzymes (e.g. transferrin, ceruloplasmin, superoxide dismutase). For a detailed review of chelating agents and the optimal match between chelator and radionuclide see Price
Structural formula of different chelators and co-ligands for radiolabeling peptides and proteins.
The introduction of BFCA in proteins or peptides can be achieved using bioconjugation methods based on reactive functional groups, such as amide coupling (carboxylic acids and their activated
Apart from planar imaging, SPECT and PET are the two main imaging modalities in nuclear medicine. SPECT imaging is much more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare, financially generally more accessible, and usually have a longer half-life than those used for PET (Table 1). Commonly used gamma emitters are: 123I (Emax 529 keV, t1/2 13.0 h), 111In (Emax 245 keV, t1/2 67.2 h), and 99mTc (Emax 141 keV, t1/2 6.02 h). Compared to SPECT, PET has the possibility to more accurately quantitate the
Isotope | Half-life (h) | Decay type | |
---|---|---|---|
γ-emitter (SPECT) | 99mTc | 6.02 | IT |
111ln | 67.2 | EC, γ | |
123l | 13.0 | EC, γ, e− | |
β+-emitter (PET) | 18F | 1.83 | β+, EC |
64Cu | 12.9 | β−, EC | |
68Ga | 1.14 | β+, EC | |
124l | 76.8 | EC, β+, γ | |
β−-emitter (therapy) | 90Y | 64.1 | β− |
177Lu | 161 | β− | |
186Re | 91 | β−, EC, γ | |
188Re | 17.0 | β− | |
131l | 192 | β−, γ, e− |
Half-life and decay type of several radionuclides.
Half-life is given in hours, unless stated otherwise. β− = negative beta decay, β+ = positive beta decay, γ = gamma transition, IT = isometric transition, EC = electron capture.
PET is independent of the location depth of the reporter probe of interest and is able to detect picomolar concentrations of tracer [7]. This high sensitivity of PET can only be matched to some degree by optical imaging (OI) techniques, but not by MRI, CT or ultrasound (US). In addition, compared to MRI and conventional optical imaging techniques, PET has the advantage of being quantitative. Though, with the introduction of fluorescence mediated tomography (FMT), quantitative measurements are also possible with OI techniques [8].
Recent developments also allow semi-quantitative measurements with SPECT, but these developments are not yet widespread and still show higher uncertainties compared to PET.
The spatial resolution of PET and SPECT scanners depends on several factors: the type of isotope (PET or SPECT), the energy of the isotope emissions, and the object being scanned. The type of isotope (positron-emitting or single-photon emitting) has a strong impact, as the image reconstruction techniques for PET are superior to those of SPECT due to physical characteristics in large objects, but this is reversed for small objects. The energy of the isotope emissions is negatively correlated to the spatial resolution: the stronger the energy, the poorer the spatial resolution. The object being scanned has a substantial impact: spatial resolution in mice is vastly superior to that in humans, and even within humans spatial resolution in obese people is worse compared to healthy subjects. Some typical spatial resolutions are: 99mTc, mouse: 0.5 mm; 99mTc, human: 10 mm; 18F, mouse: 0.8 mm; 18F, human: 2 mm; 68Ga, human and mouse: both 4 mm. The spatial resolution should be taken into account when designing studies.
Nowadays, recombinant protein expression is a routine laboratory technology that enables fast and high-yield protein production. The choice of bacterial, yeast, insect or mammalian cellular-based expression system depends on several factors such as, cell growth characteristics, intracellular and extracellular expression, posttranslational modifications, and regulatory issues of proteins used as diagnostics and therapeutics. Recently, even cell-free expression systems using purified RNA polymerase, ribosomes, tRNA and ribonucleotides have been developed [9]. Each expression system has its particular advantages and disadvantages that are relevant for the purpose of use. Several review papers give a good description of the variety of expression systems and their pros and cons. However, for development of target-specific radiotracers, fluorescent probes, or multimodality molecular imaging agents, chemical protein synthesis is the method of choice because of reasons described below. Therefore, this book chapter does not cover recombinant expression systems further.
Total chemical protein synthesis is an attractive alternative to biological protein production. Chemical peptide synthesis can be divided in: (I) liquid-phase peptide synthesis and (II) solid-phase peptide synthesis. Liquid-phase peptide synthesis is a classical approach to peptide synthesis and since the beginning of the 20th century this technique has developed considerably. Although liquid-phase peptide synthesis has some limitations due to its time consuming nature, solubility issues and the need for lengthy purification procedures, it is still useful for large-scale peptide production and for specialized laboratory applications [10].
Solid-phase peptide synthesis (SPPS) is currently the preferential technique to establish access to synthetic peptides. The general process for SPPS is based on sequential addition of α-amino and reactive side chain protected amino acids to a solid support (resin). The
The use of synthetic chemistry allows infinite variation of the polypeptide chain by for example incorporation of unnatural amino acids such as β-amino acids,
Functionalization of peptides and proteins still heavily relies on amine or thiol functionalities, present in proteins as lysine and cysteine side chains, respectively. New ligation techniques are emerging that are moving away from amines or use of protected thiols. The functionalization of lysine side chains can be achieved by reacting them with activated esters such as NHS-DTPA or –DOTA that are commercially available (Figure 2). The most appropriate derivatives of these chelators for conjugation to a peptide or protein are those which are
Conjugation at
The main advantage of these activated ester chelators is their ease of use, while the main disadvantage of this technique is their unspecific labeling. A protein generally contains more than one lysine residue and thus more than one position for chelator conjugation. It is difficult to predict the site of coupling, which will often lead to heterogenous labeling of the compound of interest. With the use of Boc SPPS this problem can be circumvented by using orthogonally ε-amino Fmoc-protected lysine residues. Deprotection of the Fmoc group can be performed on resin and directly be followed by functionalization of the desired lysine with an NHS-activated label of choice. In case of Fmoc SPPS, orthogonally ε-amino allyloxycarbonyl (Alloc) protected lysine residues can be used.
Conjugation at cysteine residues can be realized by reactions with maleimide containing compounds or 2-azidoacrylate-derivatives [13]. Similar to the amine reactive NHS esters, commercial compounds with maleimides are widespread. Maleimide-DOTA or –DTPA are coupled to free cysteine-containing proteins (Figure 3). Although the reaction is specific and easy to use, maleimides have their disadvantages. The first being the availability of a free cysteine in a protein of interest; the major part of cysteines present in proteins are paired with a second cysteine to form a disulfide bridge. Moreover, these cysteines are often buried within the core of the protein making them inaccessible for maleimides. To overcome this problem an additional cysteine can be incorporated into the protein specifically for labeling. This will, however, lead to problems with oxidative folding of the protein and can lead to improperly folded proteins with loss of activity.
Conjugation at a free thiol moiety present in cysteine using a maleimide resulting in a thioether bond.
However, this does not mean that thiol reactive compounds cannot be useful in protein labeling. The introduction of an encrypted cysteine that can be deprotected after correct folding of the protein can offer a solution. Recently
Deprotection of thiazolidinecarboxyl coupled to
Furthermore, it was shown that this technique is fully compatible with established techniques of peptide synthesis and NCL. The chemokine CCL5 was synthesized from an
Upon treatment with MeONH2 to convert the thiazolidine functionality into a free cysteine and subsequent modification with a maleimide label, unwanted disulfide shuffling can occur in proteins containing disulfide bonds [18]. To circumvent this problem a synchronized protocol for thiazolidine deprotection and maleimide coupling can be best used (Figure 5).
Schematic representation of the synthesis of chemokine CCL5. In the first step two unprotected peptide fragments are ligated using native chemical ligation. Subsequently, the peptide is folded into an active protein. In the last step the thiazolidine ring is opened while simultaneously the newly formed thiol moiety is modified with a maleimide.
A chemoselective conjugation approach that does not use any of the naturally occurring functional groups in proteins is oxime ligation. The reaction is comprised of a ketone or aldehyde reacting with an aminooxy group to yield an oxime bond (Figure 6). The reaction can be performed in aqueous media at neutral pH but is faster at slightly acidic pH [19]. The reaction can be catalyzed with aniline or derivatives thereof, to facilitate fast reactions [20, 21].
Reaction of an aminooxy with a ketone which results in an oxime bond.
Although the oxime reaction itself can be performed relatively easy, the more challenging part is the incorporation of a ketone or aminooxy in the peptide/protein of interest. Since a ketone is virtually inert to most chemical reactions, the ketone is mostly chosen over the aminooxy component to be incorporated in the protein of choice, while the aminooxy component is used to modify the label. The increased attention for the oxime bond in the last decade has led to the development of several methods to incorporate ketones or aldehydes in proteins. An overview of the available techniques was previously reviewed, here we will briefly highlight methods useful in chemical synthesis [22]. Historically, oxidation of peptides/proteins containing an
In summary, several techniques are available for the modification of proteins to include chelators used for PET and SPECT. Amine and thiol reactive compounds are easy to use through orthogonally protected lysine side chains or through thiazolidine deprotection in pre-folded proteins. Oxime conjugation can be used for chelator incorporation but is also used for covalent radiolabeling approaches, such as introducing 18F-containing prosthetic groups (see for an overview [29]).
A variety of labeling techniques can be applied to peptides and proteins, but according to George De Hevesy’s definition of a tracer the radiolabeling procedure should not affect the biological properties, the affinity to the target, or the physicochemical properties (e.g. charge, hydrophilicity, size). In the following part a list of radiosynthesis techniques for commonly used isotopes is described, omitting isotopes that are used less frequently. For example, 11C is a widespread isotope for labeling small organic compounds, but it is used less frequently in peptides or larger structures and so will therefore not be further discussed here.
Radioiodination of peptides with 125I, 123I, 124I, or 131I can be performed by either direct labeling or indirect labeling via an auxiliary group. During direct radioiodination, radioactive iodine is incorporated covalently into the side chains of tyrosyl or histidyl residues in the presence of an oxidizing agent such as chloramine-T or iodogen. If no tyrosyl or histidyl residue is available, free amino groups in the peptide may be radioiodinated by auxiliary groups, including
The auxiliary groups Bolton-hunter reagent, SIB, SIPC, and SGMIB for the radioiodination of peptides.
As none of the radioiodination methods is based on complexation with a chelator, we will not focus on this labeling method in this book chapter further.
For routine PET imaging, fluorine-18 represents the near ideal radionuclide with its half-life of 109.8 min and low β+-energy (0.64 MeV). Due to this low positron energy, it has a short positron linear range in tissue, leading to particularly high spatial resolution in PET imaging. Furthermore, compared to other short lived radionuclides, such as 11C, its half-life is long enough to allow syntheses and imaging procedures to be extended over hours, enabling kinetic studies and high-quality metabolite and plasma analysis.
Efficient 18F-labeling of peptides and proteins often comprises a multistep process involving labeling and purification of a prosthetic group (synthon) and subsequent conjugation of the 18F-labeled synthon to the peptide/protein with or without activation. If necessary, the 18F-conjugate is purified by a final purification step. Over the years, a variety of prosthetic groups have been developed ranging from amine-reactive groups such as
In spite of the variety of possibilities for introducing 18F, a major drawback of the 18F-labeling methods described above is that they are laborious, (require azeotropic drying of the fluoride and multiple purification steps) and are thus time consuming. In search of a kit-based 18F-labeling method, new 18F-labeling strategies based on fluorine-silicon [50, 51, 52, 53, 54, 55, 56], fluorine-boron [57, 58, 59], and fluorine-phosphorus [60] have been developed.
A facile chelator-based approach was developed wherein 18F is first attached to aluminum as Al18F, which is then complexed in a chelating agent attached to the peptide, forming a stable Al18F–chelate peptide complex in an efficient 1-pot process [61].
Gallium-68 is an interesting positron-emitter, because of its well established radiochemistry and its easy access and availability from commercial available 68Ge/68Ga-generators (t1/268Ge = 268 days) which renders it independent of an on-site cyclotron. The application of 68Ga-labeled peptides and proteins has attracted considerable interest for molecular imaging, because of its physical characteristics. The high positron emission fraction, 89% through positron emission of 1.9 MeV (max. energy), and half-life of 68 min allows short scanning times with sufficient amounts of radioactivity for high quality images. Generally, DOTA and NOTA are very suitable chelators and are commonly used for 68Ga3+-complexation. Though, recently TRAP (Tri-azacyclononane-phosphinic acid) and its derivatives revealed to be powerful 68Ga chelators which possess valuable utility in nuclear medicine and molecular imaging [62].
DOTA has a larger cavity than NOTA and, thus, needs higher ring distortion for complexation of 68Ga3+. Therefore, higher temperatures are required for 68Ga-DOTA complex formation compared to 68Ga complex formation with NOTA. Typically, DOTA-conjugated peptides are radiolabeled with 68Ga at 90–100°C, whereas NOTA-conjugated peptides can be labeled at room temperature [62].
Generally, 68Ga is obtained by eluting a 68Ge/68Ga generator with a 0.01–1 M HCl solution. The eluate can be added directly to the NOTA- or DOTA-conjugated compound dissolved in a suitable buffer system such as HEPES (4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid), phosphate, or ammonium acetate. It is important that the resulting pH of the reaction mixture is a pH value <4 to prevent formation of colloidal hydroxide [68Ga(OH)3]n which begins at a pH value above 4.
The SPECT isotope indium-111 is a frequently used radionuclides in diagnostic nuclear medicine. It has a physical half-life of 67 hours and is produced by a cyclotron. The principle photons are 173 keV (89%) and 247 keV (94%). The most commonly used chelators for 111In-labeling of peptides and proteins are DTPA and DOTA. DTPA chelates 111In at room temperature with sufficient efficiency and stability. This DTPA chelator is used in the commercially available somatostatin analog OctreoScan®. DOTA forms a more stable complex with 111In, but requires heating of the reaction mixture which can lead to protein denaturation, especially for larger proteins. Labeling of DTPA- and DOTA-conjugated peptides and proteins is a one pot, one step procedure in which the compound is incubated with 111InCl3 at a pH between 4 and 6. Ammonium and sodium acetate buffers are commonly used as buffer for labeling of DTPA- and DOTA-conjugated compounds with 111In. However, it was shown that 111In-labeling efficiency and specific activity of DTPA- and DOTA-conjugated peptides was significantly improved in MES (2-(
Technetium-99 m is the most widely used isotope due to its ideal half-life of 6 hours, its low cost, and excellent imaging characteristics. Similar to 68Ga, 99mTc can be obtained from a generator (99Mo/99mTc, with a half-life of 66 hours for 99Mo) which is easily shipped, allowing worldwide use. Since the 1960s, 99mTc has been used in a variety of applications, including cancer research and cardiac assessment. 99mTc is a nearly pure gamma-emitter (88%), with the remaining 12% yielding internal conversion electrons. The application is therefore restricted to SPECT imaging (although research into therapeutic applications is also performed).
Possibilities for coupling of 99mTc to small organic compounds, peptides or proteins are nearly unlimited, in part due to the many oxidation states that 99mTc can have, ranging from +I to +VII. The isotope is obtained from the generator in a pH-neutral and isotonic saline solution, ensuring computability with nearly any peptide or protein.
One solution to radiolabel proteins is, instead of chemically modifying the protein, synthesizing it with an additional hexa-histidine chain at the
An alternative for 99mTc-labeling of peptides and proteins is conjugating them with the bifunctional chelator HYNIC (6-hydrazinonicotinic acid). HYNIC has been introduced to radiolabel an IgG antibody with 99mTc for infection imaging [65]. HYNIC is an established and appropriate BCA for 99mTc-labeling, because it allows rapid and efficient labeling of proteins. In addition, 99mTc-labeled HYNIC-conjugates can be produced with high specific activities. However, conjugation of HYNIC to a peptide of protein can be complex as the hydrazine group of HYNIC is highly nucleophilic and, when unprotected, undergoes unwanted side reactions with electrophiles. Protecting the hydrazine group of HYNIC-conjugated compounds with for example Fmoc, Cbz, and Boc, has been investigated by several research groups and is still subject of current research [66, 67, 68, 69, 70, 71].
Since the HYNIC group can only coordinate to a metal through 2 donor groups at most, it is unable to saturate the technetium coordination sphere. To complete the coordination sphere, an additional coligand, such as EDDA (ethylenediamine diacetic acid), tricine (
Improvements in effective nuclear imaging are not only dependent on progression in imaging equipment and technology, but is also strongly dependent on the availability of powerful probes with optimal pharmacokinetic and imaging characteristics. The diversity of methods for syntheses of peptides and proteins and the variety of possibilities for modification, stabilization, labeling (radiolabeling and labeling for other modalities), and construction of more complex multivalent and multimodal constructs, make radiolabeled peptides and proteins a flexible class of tracers and meaningful molecules for nuclear imaging of several diseases such as cancer, thrombosis, infection, and inflammation in pre-clinical and clinical research.
Radiotracers enable early diagnosis and thus early treatment of disease and they enable better stratification of patients with disease-stage-adapted therapy instead of escalating to the most aggressive and costly therapy. Moreover, radiolabeled compounds are used to monitor the therapeutic effect of drugs and are used as therapeutic radiopharmaceuticals when labeled with either β− - or α-emitting radionuclides such as 90Y, 186Re, 188Re, 131I, 177Lu and 211At and 213Bi, respectively.
The growth of the world population and the overall rise in life expectancy in the last decades will increase the demand for radiopharmaceuticals, including basic research into and the development of new radiopharmaceuticals.
The authors declare no conflict of interest.
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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:null},{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. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. 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He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",keywords:"Anthropic effects, Overexploitation, Biodiversity loss, Degradation, Inadequate Management, SDGs adequate practices"},{id:"38",title:"Pollution",scope:"\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",keywords:"Human activity, Pollutants, Reduced risks, Population growth, Waste disposal, Remediation, Clean environment"},{id:"41",title:"Water Science",scope:"