\\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:"6972",leadTitle:null,fullTitle:"Soybean for Human Consumption and Animal Feed",title:"Soybean for Human Consumption and Animal Feed",subtitle:null,reviewType:"peer-reviewed",abstract:"Soybean is the main oilseed crop worldwide, a staple crop for protein-rich food and feed as well as a significant source of nutraceutical compounds with many different medical benefits. Soybean for Human Consumption and Animal Feed highlights the state of research in soybean nutritional attributes as well as science-based approaches defining the future of soybean for human consumption and animal feed. Over seven chapters, this book presents a comprehensive picture of the potential of soybean for human and animal diets and health as well as quality stock for pharmaceutical and functional food industries with an emphasis on the importance of genetic improvement of soybean germplasm in enhancing healthy and safe properties of final soy products.",isbn:"978-1-83881-019-1",printIsbn:"978-1-83881-018-4",pdfIsbn:"978-1-83881-020-7",doi:"10.5772/intechopen.73719",price:119,priceEur:129,priceUsd:155,slug:"soybean-for-human-consumption-and-animal-feed",numberOfPages:160,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"4bc6f95dc8630c9a8be84bb46286c445",bookSignature:"Aleksandra Sudarić",publishedDate:"December 2nd 2020",coverURL:"https://cdn.intechopen.com/books/images_new/6972.jpg",numberOfDownloads:5226,numberOfWosCitations:13,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:25,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:47,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 5th 2019",dateEndSecondStepPublish:"December 25th 2019",dateEndThirdStepPublish:"February 23rd 2020",dateEndFourthStepPublish:"May 13th 2020",dateEndFifthStepPublish:"July 12th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"21485",title:"Dr.",name:"Aleksandra",middleName:null,surname:"Sudarić",slug:"aleksandra-sudaric",fullName:"Aleksandra Sudarić",profilePictureURL:"https://mts.intechopen.com/storage/users/21485/images/system/21485.jpg",biography:"Dr. Aleksandra Sudarić was born in Osijek, Croatia. She received an MSc in Plant Genetics and Breeding in 1996 from the University of Zagreb and a PhD in Plant Breeding in 1999 from the University of Osijek. Dr. Sudarić is a senior research scientist at the Agricultural Institute Osijek (Croatia), Department for Breeding and Genetics of Industrial Plants where she studies the breeding and seed production of soybean. She is presently coordinator of the soybean breeding program at the Institute. In addition, she completed the training for application of DNA-based marker technology at the University of Guelph in Guelph (Canada). Her main research interests are in the genetic improvement of quantity and quality characteristics of soybean and soybean adaptation to mega-environments. Dr. Sudarić has authored more than 100 papers (scientific, professional, and popular), several book chapters, books, and manuscripts about soybean as well as developed twenty-six soybean varieties.",institutionString:"Agricultural Institute Osijek",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Agricultural Institute Osijek",institutionURL:null,country:{name:"Croatia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"36",title:"Food Science",slug:"food-science"}],chapters:[{id:"73415",title:"Introductory Chapter: Soybean - Quality and Utilization",doi:"10.5772/intechopen.93942",slug:"introductory-chapter-soybean-quality-and-utilization",totalDownloads:527,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Aleksandra Sudarić",downloadPdfUrl:"/chapter/pdf-download/73415",previewPdfUrl:"/chapter/pdf-preview/73415",authors:[{id:"21485",title:"Dr.",name:"Aleksandra",surname:"Sudarić",slug:"aleksandra-sudaric",fullName:"Aleksandra Sudarić"}],corrections:null},{id:"69396",title:"Soybean Amino Acids in Health, Genetics, and Evaluation",doi:"10.5772/intechopen.89497",slug:"soybean-amino-acids-in-health-genetics-and-evaluation",totalDownloads:1340,totalCrossrefCites:0,totalDimensionsCites:6,hasAltmetrics:1,abstract:"Soybean is an important source of protein and amino acids for humans and livestock because of its well-balanced amino acid profile. This chapter outlines the strengths and weaknesses of soybean as a complete amino acid source as well as the relative importance of individual amino acids. Special attention is paid to the sulfur-containing amino acids, methionine and cysteine. Breeding and genetic engineering efforts are summarized to highlight previous accomplishments in amino acid improvement and potential avenues for future research. Agronomic properties and processing methods that affect amino acid levels in soybean food and feed are also explained. A brief introduction into current amino acid evaluation techniques is provided. By understanding the complexities of amino acids in soybean, protein quality for humans and livestock can be maximized.",signatures:"William Monte Singer, Bo Zhang, M.A. Rouf Mian and Haibo Huang",downloadPdfUrl:"/chapter/pdf-download/69396",previewPdfUrl:"/chapter/pdf-preview/69396",authors:[{id:"308970",title:"Mr.",name:"William",surname:"Singer",slug:"william-singer",fullName:"William Singer"},{id:"309005",title:"Dr.",name:"Bo",surname:"Zhang",slug:"bo-zhang",fullName:"Bo Zhang"},{id:"310776",title:"Dr.",name:"M.A. Rouf",surname:"Mian",slug:"m.a.-rouf-mian",fullName:"M.A. Rouf Mian"},{id:"310777",title:"Dr.",name:"Haibo",surname:"Huang",slug:"haibo-huang",fullName:"Haibo Huang"}],corrections:null},{id:"69807",title:"Improving Seed Quality of Soybean Suitable for Growing in Europe",doi:"10.5772/intechopen.89922",slug:"improving-seed-quality-of-soybean-suitable-for-growing-in-europe",totalDownloads:991,totalCrossrefCites:3,totalDimensionsCites:7,hasAltmetrics:0,abstract:"The potential of soybean for food, feed, and pharmaceutical industry arises from the composition of its seed. Since European countries import 95% of the annual demand for soybean grains, meal, and oil, causing an enormous trade deficit, the governments in Europe had started to introduce additional incentives to stimulate soybean cropping. To rebalance the sources of soybean supply in the future, production must be followed by continuous research to create varieties that would make European soybean more appealing to the processing industry and profitable enough to satisfy European farmers. This chapter is giving an overview of the European soybean seed quality research and an insight into soybean seed quality progress made at the Agricultural Institute Osijek, Croatia. The studies presented are mainly considering maturity groups suitable for growing in almost all European regions. The most important traits of soybean seed quality discussed are protein content and amino acid composition, oil content and fatty acid composition, soluble sugars, and isoflavones. Defining quality traits facilitates the parental selection in breeding programs aiming to improve the added value properties of final soybean products and enables the exchange of materials between different breeding and research institutions to introduce diversity, which is a prerequisite for genetic advance.",signatures:"Aleksandra Sudarić, Maja Matoša Kočar, Tomislav Duvnjak, Zvonimir Zdunić and Antonela Markulj Kulundžić",downloadPdfUrl:"/chapter/pdf-download/69807",previewPdfUrl:"/chapter/pdf-preview/69807",authors:[{id:"21485",title:"Dr.",name:"Aleksandra",surname:"Sudarić",slug:"aleksandra-sudaric",fullName:"Aleksandra Sudarić"},{id:"311324",title:"Dr.",name:"Maja",surname:"Matoša Kočar",slug:"maja-matosa-kocar",fullName:"Maja Matoša Kočar"},{id:"311331",title:"Dr.",name:"Tomislav",surname:"Duvnjak",slug:"tomislav-duvnjak",fullName:"Tomislav Duvnjak"},{id:"311332",title:"Dr.",name:"Zvonimir",surname:"Zdunić",slug:"zvonimir-zdunic",fullName:"Zvonimir Zdunić"},{id:"311333",title:"Dr.",name:"Antonela",surname:"Markulj Kulundžić",slug:"antonela-markulj-kulundzic",fullName:"Antonela Markulj Kulundžić"}],corrections:null},{id:"72688",title:"Respiratory Health Risks from Exposure to Dust from Soybean and Its Products",doi:"10.5772/intechopen.92839",slug:"respiratory-health-risks-from-exposure-to-dust-from-soybean-and-its-products",totalDownloads:755,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Soybean and its processed forms have become an increasingly important part of agriculture, where they are widely used as an animal feedstuff and in an extensive range of human food products. This entails transportation from producer countries, largely the USA and South America, to importer destinations such as the EU and China. Soya is recognised as a dietary allergen, containing a number of identified allergenic proteins. Inhaled soya dust generated by occupational activities also causes respiratory health problems. Reports of “asthma epidemics” in harbour cities identified ill health in the community but were related to occupational activities of unloading/loading bulk soya without appropriate dust control measures. Inhaled allergens in already-sensitised individuals can cause a range of allergic symptoms in the eyes, nose, and respiratory tract, including occupational asthma (OA). Soybean dust can also cause health problems related to lung irritancy. Endotoxin and fungal contamination associated with soya are also potential respiratory hazards. This chapter reviews published data on ill health and symptoms from airborne exposure to allergens in dust from soybean and derivative products and the levels of exposure to dust and major allergens from a range of occupational activities. Other potential health hazards associated with soybean, such as endotoxin and fungal contamination, are also highlighted.",signatures:"Howard J. Mason",downloadPdfUrl:"/chapter/pdf-download/72688",previewPdfUrl:"/chapter/pdf-preview/72688",authors:[{id:"317237",title:"Dr.",name:"Howard",surname:"Mason",slug:"howard-mason",fullName:"Howard Mason"}],corrections:null},{id:"72429",title:"The Potential Impacts of Soy Protein on Fish Gut Health",doi:"10.5772/intechopen.92695",slug:"the-potential-impacts-of-soy-protein-on-fish-gut-health",totalDownloads:593,totalCrossrefCites:6,totalDimensionsCites:12,hasAltmetrics:1,abstract:"Soy protein is the major source of protein as fishmeal replacement in fish feed because of its worldwide availability and low price. However, the presence of high carbohydrate content along with saponins, lectins, and phytates can have a negative impact on fish gut health. Based on the literature and our lab studies, dietary soybean meal can cause a dose-dependent type of distal intestine inflammation called enteritis in commercial fish species including salmonids. This leads to reduced absorptive capacity, increased mucus secretion, hyperpermeability, and leucocyte infiltration in the lamina propria and submucosa, also inducing the pro-inflammatory cytokine genes expression, including Il-1β, Il-8, and Tnf-α. In addition, dietary soy may alter the composition and population of the gut microbiota via providing nutrients and energy that preferentially support the growth of some gut bacteria. This chapter summarizes the current knowledge of the effects of soy protein on the enteritis and gut microbiota.",signatures:"Vikas Kumar, Md. Sakhawat Hossain, Janice A. Ragaza and Marina Rubio Benito",downloadPdfUrl:"/chapter/pdf-download/72429",previewPdfUrl:"/chapter/pdf-preview/72429",authors:[{id:"310392",title:"Prof.",name:"Vikas",surname:"Kumar",slug:"vikas-kumar",fullName:"Vikas Kumar"},{id:"310393",title:"MSc.",name:"Marina",surname:"Benito",slug:"marina-benito",fullName:"Marina Benito"},{id:"318034",title:"Dr.",name:"Md. Sakhawat",surname:"Hossain",slug:"md.-sakhawat-hossain",fullName:"Md. Sakhawat Hossain"},{id:"318035",title:"Dr.",name:"Janice",surname:"Ragaza",slug:"janice-ragaza",fullName:"Janice Ragaza"}],corrections:null},{id:"68701",title:"Nondestructive Evaluation of Inoculation Effects of AMF and Bradyrhizobium japonicum on Soybean under Drought Stress From Reflectance Spectroscopy",doi:"10.5772/intechopen.88673",slug:"nondestructive-evaluation-of-inoculation-effects-of-amf-and-em-bradyrhizobium-japonicum-em-on-soybea",totalDownloads:575,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Precise estimation of leaf chlorophyll content (LCC) and leaf water content (LWC) of soybean, using remote sensing technology, provides a new avenue for the nondestructive evaluation of inoculation effects of arbuscular mycorrhizal fungi (AMF) and Bradyrhizobium japonicum (BJ) on soybean growth condition. In this study, a series of pot experiments were conducted in the greenhouse, soybean inoculated with Glomus intraradices (G.i, one of AMF species), G.i and BJ, and non-inoculation were planted under drought stress (DS) and normal irrigation (NI) conditions. Leaf spectra and LCC and LWC were measured on the 28th and 56th days after inoculation. Two new simple ratio (SR) indices, derived from the first derivative spectral reflectance at λ1 nm (Dλ1) and the raw spectral reflectance at λ2 nm (Rλ2), were developed to estimate LCC and LWC. The results indicate that under DS, plants inoculated with G.i had higher LCC and LWC than the non-inoculated plants, followed by the counterparts co-inoculated with G.i and BJ. Linear estimation models, established by the D650/Rred edge and D1680/R680, achieved great improved accuracy for quantifying LCC and LWC of soybean under inoculation and drought stress treatments, with determination of coefficient of 0.63 and 0.76, respectively.",signatures:"Weiping Kong, Yinli Bi, Wenjiang Huang, Lingli Tang, Chuanrong Li and Lingling Ma",downloadPdfUrl:"/chapter/pdf-download/68701",previewPdfUrl:"/chapter/pdf-preview/68701",authors:[{id:"247987",title:"Prof.",name:"Wenjiang",surname:"Huang",slug:"wenjiang-huang",fullName:"Wenjiang Huang"},{id:"250651",title:"Dr.",name:"Weiping",surname:"Kong",slug:"weiping-kong",fullName:"Weiping Kong"},{id:"308543",title:"Dr.",name:"Yinli",surname:"Bi",slug:"yinli-bi",fullName:"Yinli Bi"}],corrections:null},{id:"73649",title:"Soybean (Glycine max (L.) Merr.) Production in the Cameroonian Cotton Basin between the Dynamics of Structuring an Agricultural Value Chain and Sustainability Issues",doi:"10.5772/intechopen.93981",slug:"soybean-em-glycine-max-em-em-l-em-em-merr-em-production-in-the-cameroonian-cotton-basin-between-the-",totalDownloads:449,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Over the past ten years, the Cameroonian cotton front, in the Sudano-Sahelian region, has experienced dynamics in soybean production, resulting in significant changes in agro-systems. From a simple hut culture not referenced in regional agricultural statistics, since 2010, soybean ranks 2nd in legumes cultivated after peanuts, followed by cowpea and voandzou, yet culturally and economically more adopted by the populations. The rapid development of cultivated areas from 6,705 ha in 2008 to 15,020 ha in 2018 is indicative of the enthusiasm shown by farmers for this speculation which, despite the almost lack of supervision on the part of public authorities, now structures a real value chain with challenges for improving farmers’ incomes, in a space where more than 80% of working people live from agricultural activities. The objective of this research is therefore to analyse the sustainability challenges of a productive and market dynamics built around speculation subject to strong demands of international competitiveness. The results show that the viability of this dynamics remains precarious through a set of constraints inherent in the proven inability of farmers to empower themselves to optimise production and control marketing, as well as the poor technical supervision of cultivation.",signatures:"Eric Joël Fofiri Nzossié and Christophe Bring",downloadPdfUrl:"/chapter/pdf-download/73649",previewPdfUrl:"/chapter/pdf-preview/73649",authors:[{id:"320682",title:"Dr.",name:"Eric Joël",surname:"Fofiri Nzossie",slug:"eric-joel-fofiri-nzossie",fullName:"Eric Joël Fofiri Nzossie"},{id:"320685",title:"Prof.",name:"Christophe",surname:"Bring",slug:"christophe-bring",fullName:"Christophe Bring"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"1484",title:"Soybean",subtitle:"Molecular Aspects of Breeding",isOpenForSubmission:!1,hash:"3bd8fd078e7df24f2eed6dc7bc226475",slug:"soybean-molecular-aspects-of-breeding",bookSignature:"Aleksandra Sudaric",coverURL:"https://cdn.intechopen.com/books/images_new/1484.jpg",editedByType:"Edited by",editors:[{id:"21485",title:"Dr.",name:"Aleksandra",surname:"Sudarić",slug:"aleksandra-sudaric",fullName:"Aleksandra Sudarić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10237",title:"Innovation in the Food Sector Through the Valorization of Food and Agro-Food By-Products",subtitle:null,isOpenForSubmission:!1,hash:"c3a5a3c7f7999d68f04ae49ff0553f3d",slug:"innovation-in-the-food-sector-through-the-valorization-of-food-and-agro-food-by-products",bookSignature:"Ana Novo de Barros and Irene Gouvinhas",coverURL:"https://cdn.intechopen.com/books/images_new/10237.jpg",editedByType:"Edited by",editors:[{id:"260510",title:"Prof.",name:"Ana",surname:"Novo de Barros",slug:"ana-novo-de-barros",fullName:"Ana Novo de Barros"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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2019",datePublished:"February 10th 2021",book:{id:"8558",title:"Aerodynamics",subtitle:null,fullTitle:"Aerodynamics",slug:"aerodynamics",publishedDate:"February 10th 2021",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"169258",title:"Dr.",name:"Patricia",middleName:null,surname:"Popoola",fullName:"Patricia Popoola",slug:"patricia-popoola",email:"popoolaapi@tut.ac.za",position:null,institution:{name:"Tshwane University of Technology",institutionURL:null,country:{name:"South Africa"}}},{id:"176896",title:"Dr.",name:"Sisa",middleName:null,surname:"Pityana",fullName:"Sisa 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He received his Ph.D. degree in Mechanical Engineering from Tongji University in 2004. From 1995 to 2001, he was the manager in the Business and Warehousing Management Departments of Guilin Daewoo Bus Co., LTD. He is a Director of Intelligent Manufacturing and Services Branch of China Creative Studies Institute and Director of East China Branch of National College Institute of Manufacturing Automation. Dr. Li’s research interests include intelligent manufacturing systems and quality control technology in manufacturing. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"65647",title:"Television as a Surveillance Tool",doi:"10.5772/intechopen.83532",slug:"television-as-a-surveillance-tool",body:'\nTelevision (TV) that became a ubiquitous part of households in many parts of the world since World War II has been witnessing a significant transformation since the turn of the twenty-first century. Starting in the early 2000s, TV has morphed in many ways such as in the size and quality of picture it delivers, the kind of content it can offer, and the multiple ways in which it can be used.1 Yet, in spite of these changes, it has been the case that TV has remained a site to consume narratives.2 Within the narrative paradigm, narratives, as pointed out in the work of Fisher [7, 8, 9] and later in the research on narrative bits [10, 11, 12, 13], are also windows to the lives of individuals and groups. While TV has brought narratives home, the knowledge of the narratives of people can allow one to better understand the person and predict and control what the person may do. This perspective on narrative suggests that every person has a “life story,” and access to that story offers an insight into the person’s life. The challenge has been accessing the story in detail. Creating a detailed narrative requires constantly watching the person and tracking the person’s beliefs, interests, and behavior. The matter of watching and constructing the narrative was eased when the advent of the digital allowed the analog, flesh-and-blood person, to construct a digital representation of the self in the digital space. This was akin to creating the life story online, which could be the repository of the narrative of the person. Indeed, this is the realm of big data [14, 15]. In this essay I argue that TV, originally the conduit for offering passive narratives to the audience, is transforming into a tool that can watch over the audience and construct a dynamic narrative of the audience, thus operating as tool for surveillance.
\nSince the early days of TV in the developed countries of the West, technology and medium had been considered to be a passive device that was the conduit that brought information to the people who would watch the screen seeking anything from entertainment to education. TV has sometimes been called the “idiot tube,” for the mesmerizing effect it would have on the watcher who could be distracted to catatonic inactivity just watching TV in a “mindless” way without having to bring any intellectual energy to the process of watching TV. This phenomenon was examined copiously by scholars from many disciplines, and numerous theories were proposed and debated that examined the “effects” of watching TV as would be found in many introductory books on mass communication.
\nOne important assumption that underpinned the emergent theories claimed that the audience of TV was a relatively passive and often disengaged person (see, e.g., early research by Klapper [16]). This assumption was especially true for the programs of research that mimicked the natural scientific methods of research devising experiments and interventions with samples selected from the population to understand the effects of TV in numerical terms, as in the case of development of theories such as cultivation theory often considered to be a central tenet of understanding the effect of TV. Other researchers who subscribed to a more cultural anthropological, critical, and cultural interpretations of the role of TV in everyday life sought answers in the ways the audience would talk about television or through observational studies where the audience would be observed to see how they interacted with the narratives and discourses on television, as in the case of scholar originating in the Birmingham Centre for Cultural Studies and offering the vast array of literature on the role of TV within popular culture starting with the work of scholars such as [17]. In both approaches, however, there was the shared presumption of relative anonymity of the audience where any individual member of the audience was a part of a larger similar kind of people where the specific individual was unknown to those who created and circulated the content of TV. This presumption worked well for the industry because the content producers were only concerned with creating content that could be of appeal to a certain type of audience and not to any individual person since there was no definitive way of knowing who the person was.
\nThis lack of information about a specific member of the audience was largely a factor of the way in which TV technology worked from its inception to the time when the Internet became a part of everyday life for large groups of people. Traditional TV technology was designed to deliver a robust image and sound to the audience without the audience having to come to the place where the content was available as in the case of movies. Like its predecessor—radio, TV brought the message to the home of the audience. The content distributors had little knowledge of who was watching the content, why they were watching the content, or if the audience was liking the content. For the content distributors such as the NBCs and BBCs, once the content left the antennas, there was no way to “control” the content and trace where it went or what happened to the content. At the reception end of the process, TV technology was a “passive” tool that merely displayed the content on the screen. Once the TV was turned off, the screen was just a part of the furniture in the room. This status quo changed with the increasing adoption of the Internet in the public sphere.
\nFor a length of time, the television screen achieved a sense of status quo until around the 1980s when one of the key quests was to push the size of the screen so that a cinema-like experience could be reproduced in the privacy of homes for those who could afford the huge back-projection units that often had pictures of poor quality. This trend to improve the picture quality continued for decades.
\nHowever, a change started to happen in homes of the developed nations in the latter part of the 1990s, and by the 2000s, there was an increasing interest in a different screen that had made its way into the households of the developed nations—the computer monitor—very similar in technology to TV but often only available for displaying text that would appear on the screen in monochrome. However, the magic of the computer screen was in the fact that there was an additional device, the computer, which was connected to the screen that allowed the user of the computer screen to interact with the screen unlike the user of TV screen who merely viewed the screen. This change was especially important, because the interaction produced an active audience who could personalize the experience of using the screen. Even if the use was restricted to typing words on the screen, it was a different form of interaction with a device that looked similar to TV screen that the user was already accustomed to.
\nThis interactivity with the computer screen progressed in several different directions in the early part of the twenty-first century. With increasing home-based access to the digital network of global computers—the Internet—the interactive computer screen became a conduit to a larger virtual space with increasing libraries of data that the user could access. This data, often residing on computers all over the world, could be accessed by any of the computers using the computer screen. Even though the computer and the TV screen were beginning to look similar, their functions were constantly diverging with the TV screen becoming a site for narratives that the user could not control. The narratives of the TV screen were simply sent out to the user with the expectation that the user would subscribe to the narratives when the screen brought them home; indeed, the users were expected to manage the everyday life practices of their lives to suit the demands of the TV screen if the users wanted to access the narratives on the TV screen. Therefore, people would plan their evenings around the shows they would watch on TV [2]. On the other hand, the narratives were within the control of the user on the computer screen. Here, the user could build an unending narrative by accessing multiple data that were connected by hypertext to each other allowing the user to constantly explore, discover, and construct the personalized narrative that the user sought and not what the TV institutions handed out.
\nThe seduction of interactivity, coupled with the primacy of the computer screen over the TV screen, led to the demand for a single-screen solution where the screens could be merged into one where the single screen would serve primarily as a conduit for interactions that would allow the user to construct their personalized narrative that would appear on this single converged screen. It is this demand for convergence that allowed the ubiquitous merged screen to become a site for collecting data about individuals.3
\nThe notion of convergence is particularly important in the context of the emergent screen in the private spaces occupied by individual members of the audience. The duality between computer screen as a site with the potential of creating an interactive narrative, such as writing a book, and the TV screen as a site of consuming narrative was increasingly being erased as a single converged screen was replacing the two where the single screen would converge the different functions into one site. The notion of technological convergence precisely states that new tools often diminish the need for multiple tools with multiple functions into a single tool that offers the convenience of doing many functions with one gadget.4
\nThe new digital TV with access to the Internet built into TV was becoming commonplace by the early 2000s and became nearly ubiquitous within 5–6 years, especially in the USA where all TV broadcast changed to digital broadcast on June 12, 2009, and nearly 97.5% of the American homes were ready for the mandatory transition.5 Within the next several years, the transition to digital TV, the nearly ubiquitous availability of broadband connection to the Internet, and the emergence of content conglomerators, producers, and distributors that were distinct from the traditional media content providers offered new narratives to the audience. Thus, the dominance of corporations such as Netflix, Amazon, Hulu, YouTube, and others less prominent institutions allowed for narratives to be converged on the now-interactive screen in the private home. The narratives could now smoothly travel from the screen of the smartphone to the screen of a tablet computer, to the screen in the living room, to the projection system in the den, to the screen on the back of the driver seat in a car, and to the seat-back screen on a transcontinental flight. The same narrative was available everywhere.
\nThis narrative was also partially composed by the viewer and could be completely distinct from the narratives composed and consumed by other viewers. This narrative had a distinct characteristic of interactivity that was missing in the traditional TV narrative.
\nThe notion of interactivity, as proposed here, is derived from the way TV narratives have traditionally worked. In discussing the “flow” of television, it has been suggested that the programming decisions by the traditional TV content providers, from the CNNs to the BBCs, were thoughtfully made to construct an intertextual narrative that would span an evening of watching TV where the passive viewer has no little choice but to follow the narrative pattern constructed by a network. The availability of hundreds of TV channels, and the simple remote control, allowed viewers to “interact” with the narrative, create a partially customized narrative by switching between channels, and construct a narrative that gratified the audience, albeit within the limits of what was available on the channels. The availability of recording technology from the traditional VCR to the DVRs allowed users to shift the viewing time to one under the control of the viewer and watch only the narratives that the individual viewer was interested in.
\nThe popularity of the Internet, accompanied with the availability of content producers and distributors mentioned earlier, however, altered the way in which the viewer could interactively construct narratives. First, it became far simpler to shift the viewing time, an advantage that was already available through the more elaborate home-based recording technologies. The viewer now had the ability to seek and find narratives at any time the viewer wanted to consume narratives. The boundaries of space and time were disrupted because the ubiquitous connectivity to the Internet through multitude of digital devices, some of which were portable, allowed the viewer to call upon programs and narratives anywhere and anytime the individual wanted. Second, the narratives could be obtained from a multitude of sources where the viewer was no longer restricted to the traditional providers of narratives such as the TV channels. The increasing digitization of video (and audio) allowed for narratives to be obtained from sources that would never be considered providers of narratives, including noninstitutional sources that could not have afforded to be in the public sphere before the availability of the Internet. In particular, YouTube is the example of the worldwide video-sharing platform. A viewer could now call upon narratives that were from individual composers of narratives who would never be found in the traditional media spaces. All that was needed was the ability to do the appropriate queries to yield the kinds of narratives that the viewer was interested in. Third, the viewer could interact with multiple sources of narratives and create a customized “playlist” that specifically would be designed to meet the interest of the viewer and could be distinct from other viewers. Even though the viewer was still restricted to the narratives that were connected to the network, the choice was sufficiently large that a viewer could construct a very specific playlist to satisfy the “taste” of the viewer. Finally, all of the narratives, and the queries that create the conglomeration of narratives, could now be done through the interface of the TV screen which transformed from the passive screen to a site of interaction between narratives and the viewer.
\nThe common theme for this transformation is the interactive power attributed to the viewer with the privilege of being able to search for the narratives based on the interests of the viewer. It is precisely this interactivity, now happening through the press of buttons on a TV remote control, that transforms the relationship between the viewer and the TV screen which now serves as the gateway for the vast digital space where content is located. It is precisely the nature of the gateway that makes the TV screen the window into the world of the individual viewer who, while watching the narratives, is also being “watched” by the TV screen.
\nIn February 2018, an analysis by the reputed magazine
It is useful to briefly consider the way in which the process of surveillance has been examined over a period of time. The practice of surveillance has been around since the times that people wanted to “watch over” others. The need to watch has most importantly been related to the notion of security where the watcher has been concerned about the fact that the watched poses a threat to the interests of the watcher. Those interests could be intertwined with the interests of the watched as well; thus, the process of watching becomes particularly important to maintain a sense of order within a specific societal system. Indeed, this perspective was aptly summarized by Mike Rogers, the chairman of the intelligence committee in the American House of Representatives, following the embarrassing report in 2013 that the National Security Agency (NSA) was surveilling the phone conversations of European leaders such as Angela Merkel. Mr. Rogers was quoted to have said, “It’s a good thing. it keeps the French safe. It keeps the US safe. It keeps our European allies safe.” [19]
\nThe intimate connection between the maintenance of order and discipline becomes the central thesis of the academic examination of the process of surveillance when scholars such as Foucault [20] begin to connect surveillance to power and discipline. Among the different ideas of surveillance that emerged as important was the notion of the Panopticon which claims that the powerful is constantly watching everything all the time [21]. The Panopticon society was built around a strict definition of discipline, and in the late 1800s and early 1900s, the metaphor was principally used to describe the ways in which totalitarian nations and despots would want to constantly watch everything to maintain power and discipline (see, e.g., [21, 22, 23, 24, 25, 26, 27]).
\nIn some cases, however, there is the emergent interest in examining how the watchers could also include corporations and institutions that had a motive unrelated to discipline and power but more interested in understanding the “market” that the institution would be interested in serving (see, e.g., [28]). This is especially true for the type of interactive technologies described in this essay. The advent of the technologies described earlier in this essay is, however, concerned with the corporate watching rather than the discipline- and power-based Panopticon world that earlier scholars were concerned with. TV in the house is now constantly watching and monitoring the individuals that use TV not to stop sedition or to exercise power over the watched but to better understand the “taste” of the watched to ensure that the watcher can best deliver content to the watched that the watched is most likely to consume. In a transactional system where commodities would be sold for profit the process of TV watching, the audience is to better commodify the audience who can then be sold to appropriate institutions as a part of a potential market. The point of interest in this transaction is not the seditious behavior of the individual, as in the case of cameras watching for shoplifters in large shopping areas, but more in constructing the life story of the individual to analyze and predict what the individual may like to consume. The process of watching is thus tied to creating the life story of the audience that TV can obtain by “watching” the data that the individual generates. The data was being generated for a long period of time through a variety of digital tools that a person could be using, but TV converged all the functions of data collection into one console which increasingly becomes ubiquitous in the life of most individuals in the developed and developing worlds. The Panopticon TV in the living room is thus watching a set of different things that early surveillance studies have pointed toward, albeit no longer in the context of discipline and power.
\nThe new Panopticon created by TV at home is however less about discipline and power and much more about the way in which the “customer” who is being watched can be analyzed as a commodity who can be sold to those that are interested in selling to the watched. Simultaneously, the Panopticon condition becomes far more benign and perhaps even comforting to the watched by creating a cocoon of comfort within which the watched can dwell, where the cocoon is created by the TV itself. This process is possible because the customer voluntarily interacts with the TV by offering information to the TV and the vast array of interests that the TV represents. There are broadly two kinds of information that the watched offers to the watcher through the modern television—attitudes and behavior.
\nThe information about the attitudes, interests, beliefs, and tastes is offered by the specific discourse the watched offers to the different providers of information that bring content to the TV. Consider, for instance, the simple act of accessing a digital video service such as YouTube that can be accessed on a smartphone and then projected on the TV. In some cases, the TV itself would offer the option of connecting directly to a service such as YouTube. Indeed, it is estimated that nearly 80% of TVs in American homes would be connected to the Internet by 2019 and any TV that is connected to the Internet can potentially be accessing YouTube without the need for any other ancillary device.8 This connection makes TV the conduit for the vast amount of data available on YouTube as well as many other segments of the digital space that contain searchable data. One of the key aspects of this connection is the ability of the person being watched search for specific kind of content that can be accessed by TV and displayed on the screen. The person inscribes attitudes and preferences in the language of the search. Companies like Google have been using similar information for a long time and are thus able to offer personalized advertising when a person is working on a computer. There are ways in which such personalization of marketing messages can be turned off through the adjustment of specific settings on an application provided by a corporation. The matter becomes a little different on TV where the very purpose of the tool, the TV, is to watch narratives, and in the environment of services such as YouTube, the viewer must reveal interest information to customize what the person is watching or interested in watching. The process of using TV to access narrative content is intimately connected with the process of revealing to TV the watcher’s interests, attitudes, and beliefs.
\nThis information is also connected with the disclosure of behavior patterns. Given that much of the consumption of the content is happening through the content providers such as YouTube, Hulu, Netflix, and other Internet-based content delivery systems, there is a constant record of what was watched, when it was watched, how it was paid for, and in some cases greater granular information related to the particular watcher in a multi-people home. For instance, Netflix offers the opportunity to set up multiple subaccounts under one primary account for each member of the household, and the data that is built up actually shows which particular person was actually using specific content. In homes that have multiple TVs, it is also possible to surveil which particular TV was being used to watch what content offering a detailed understanding of the specific members who are being watched by the corporations through the conduit of TV.
\nThe attitude and behavior data that such surveillance offers eventually become a narrative about the people who are being watched over. It is this narrative that becomes especially important in the new Panopticon system produced by the modern TV.
\nAs suggested in the opening of this essay, analog person has increasingly been supplemented by the digital self where the latter can be constructed as a story about a person using the data that is produced by the analog being. The surveillance that the TV does within the privacy of the home is geared toward the construction of that narrative. A specific and unique narrative is produced by the Panopticon TV which examines the different aspects of the life of a person, and this life story of the person becomes a part of the analog person itself. This narrative can be quite detailed with some specific characteristic because of the number of different aspects of a person’s life that is being watched by the TV as indicated earlier.
\nFirst, the narrative is cumulative. TV is constantly watching and updating the narrative. Every time an individual interacts with the TV, a new segment is being added to the narrative of the life of the person. This process is similar to the way in which other data about an individual is constantly updated, as in the case of the combination of location based on Global Positioning System (GPS) and applications that offer mapping information such as Google Maps. These applications retain the records of the movement of a cell phone through space and are thus constantly updated offering a “time line” of spaces that a person might have inhabited.9 The TV surveillance operates in a similar way because the attitude and behavior data being collected by the TV is also constantly updated and the ongoing narrative of the life of a person is stored for future reference. This certainly has its advantages, where a viewer can, for instance, resume watching a show from where it was left off, offering the Panopticon TV an opportunity to see how the “rhythm” of a person’s life unfolds on a moment-to-moment basis. Similarly, because TV knows the story of a person’s life, it knows, through its applications, what the person may like to watch next with very well throughout suggestions being offered by the TV with respect to what entertainment the watched individual may be encouraged to watch. The TV watcher’s life story is now known to the TV, and TV can gently help to shape that story to reinforce the elements of the story that have been prominent over time. Thus, a person who watched a few episodes of a science fiction would be encouraged to watch other shows belonging to the same genre.
\nThe longitude of the narrative is also connected with the way in which an attempt is constantly made by the different tools of surveillance, including TV, to triangulate the data to create a narrative about the individual which would encompass
The second important aspect pointed out in these and numerous other such instructions is that the user, or the watched, is offering the data to construct the narrative. There are no hidden cameras or stealthy sensors that are surreptitiously watching the person. On the other hand, the person chose to find the convenience of talking to the TV and thus voluntarily obtained the devices and the applications which help to create the dynamic narrative that eventually makes the life of the person more comfortable. Indeed, this comfort is best maintained if the person’s life story is fully known to the Panopticon TV and its army of other devices that is constantly updating the narrative of the person and creating the zone of comfort for the person that eventually becomes comfort for the analog self where the digital narrative helps to predict what the analog self needs. Consider, for instance, the notion of Internet of Things (IoT) that hopes to convert information from and about every device that surrounds an individual to a centralized interconnected database about the person making the life story as complete as possible. When such projects come to fruition, the surveillance, aided by the voluntary data offered by the individual, would transcend the TV. In that future, all devices, including TV, would be geared to collating the most complete life story of the watched.
\nThere are a few things worthy of note with respect to the way in which TV has transformed into a tool for watching the watcher. First, this process has not been forced upon a population who had no option but to be watched. A small amount of knowledge about the ways in which the tools are watching us can allow us to shut off the surveillance. None of these tools, including TV, makes the data collection process a “required” activity to use the tool in its basic and rudimentary way. One can certainly watch television shows broadcast “over the air” without connecting the TV to the Internet. In a similar way, it is possible to use the Alexa speaker as only a portable speaker connected to a smartphone that has music stored in it. Indeed, even a smartphone can be used to make phone calls only without connecting it to the digital realm.
\nHowever, as these examples show, when a user chooses to not connect the TV to the Internet, or Alexa to its manufacturer, and the smartphone to a data plan, the user is sacrificing the ability to use the tools to their full potential. Additionally, the user is sacrificing access to the numerous programming options offered through these tools. There is, therefore, a constant tension between the inclination to maintain a sense of privacy while watching TV and retaining the convenience of the TV making suggestions about what would be interesting to watch. If TV is allowed to surveil, and it is connected with the other tools that surround the TV, then it will eventually be able to create an increasingly complete life story of the person who uses TV. This complete life story could become the way in which TV constructs a mediated reality for the person who is being watched. As discussed earlier, this reality can become progressively myopic and an echo chamber within which the person would reside while the Panopticon TV creates the comfortable media space for the person.
\nThis future is increasingly realistic since the function of TV as the bearer of the programs offered “over the air” or even through the cable system that became commonplace in the 1980s is quickly shifting. In many parts of the world, there is the increasing tendency to “cut the cord” and get rid of the cable delivery of programming. Cable companies are increasingly facing a threat where the centrality of program delivery by cable is being replaced by program delivery via the Internet. Numerous companies such as Amazon, Roku, and Apple are offering accessories that could be connected to the TV, and program would be delivered through the connection of the accessory to the Internet. Thus, a Roku “stick” can connect to the Internet, and the programs would be offered by Roku in collaboration with other content aggregators such as Sling, YouTube, and Hulu, to name a few. In some cases, a complete ecosystem is produced by a company like Amazon that would offer the accessory for TV, a household voice activated information retrieval system such as Alexa, and content through the vast store of content that Amazon owns. As the user is migrating to these options, the user is also required to share information through the conduit of the TV with all these different corporations that continue to watch the watcher. It is indeed a world of constant surveillance, whenever the TV is switched on.
\nHuntington’s disease (HD, OMIM 143100) is a rare and incurable hereditary autosomal dominant neurodegenerative disorder, affecting 5–10 individuals per 100,000 in the Caucasian population. In certain regions, such as Australia, North America, and Western Europe, including the United Kingdom, the prevalence of the disease has increased over the past 50 years [1, 2].
HD is characterized by the loss of specific neurons within the striatum. The most sensitive cell population is the gamma-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs). Neuropathologically, the disease leads to about 57% loss of cross-sectional area from the caudate nucleus and about 65% loss of the putamen (in
HD is caused by the expansion of trinucleotide Cytosine-Adenine-Guanine (CAG) repeat, located in the first exon of the HD gene, also known as HTT or IT15 gene (locus 4p16.3, OMIM 613004), which encodes the huntingtin protein (Htt). Since the discovery of HTT gene mutation (in 1993), it has been recognized that larger CAG expansions are associated with early-onset in HD, especially for AOHD. Generally, unaffected individuals have less than 35 CAG repeats (common rage in humans: 17–25), while affected individuals have 36–250 CAG repeats. The CAG repeat range of 36–39 might be found in affected individuals and asymptomatic individuals (reduced penetrance alleles), whereas individuals with over 40 CAG repeats always develop the disease (fully penetrance alleles) [4].
The wild-type allele of the HTT gene (i.e., <35 CAG repeats) typically segregates and stably as a polymorphic locus. However, the allele carrying higher-normal CAG repeats (27–35 repeats) has increased instability. For this reason, individuals with 27–35 CAG repeats have a high risk of passing on repeats in the affected size range to their offspring. HTT gene encodes the huntingtin protein (Htt), a sizeable soluble protein (350 kDa), consisting of 3114 amino acids, which is expressed in all metazoans, is highly conserved among vertebrates. Although, all tissues ubiquitously express the HTT gene, Htt protein is found higher expressed in the brain, represented by all neurons and glial cells [4].
The Htt protein is crucial for developing and maintaining central nervous systems (CNS) homeostasis since the protein is engaged in many cellular and biological functions, including transcription, transport, vesicular trafficking, and coordination of cell division, energy metabolism, and antiapoptotic activity. For this reason, it is not surprised that Htt co-localizes with many organelles, such as the nucleus, endoplasmic reticulum, Golgi complex, endosomes, mitochondria, and synaptic vesicles. Furthermore, cells expressing mRNA of the HTT gene were described by in situ hybridization in the usual human 20 to 23-week fetal brain, suggesting that huntingtin protein is crucial for the development of the CNS. Studies also demonstrated that the deletion of the mouse homolog of the HTT gene is lethal in the embryo before the brain is formed. By contrast, heterozygote mice for the HTT gene usually develop but exhibit motor deficits and cell loss in basal ganglia. Altogether, these data confirm that the Htt protein is mandatory for CNS development and function [5].
The Htt protein is characterized by the presence of (i) the N-terminal 17 amino acids (or N17 region), which is followed by (ii) the polyglutamine (poly Q) tract (encoded by the CAG repeats), (iii) a proline-rich region (PRR), (iii) clusters of Huntingtin, Elongation factor 3, PR65/A regulatory subunit of PP2A and target of rapamycin 1 (HEAT) repeats (α-helix-loop-α-helix motif), and (iv) caspase and calpain cleavage sites (in higher vertebrates). The N17 region has been identified as a critical region that plays a role in Htt localization, aggregation, and toxicity. It is subject to several post-translational modifications, including acetylation, SUMOylation, phosphorylation, and ubiquitination. The polyQ tract is encoded by the CAG trinucleotide repeats, which code for the glutamine (Q) amino acid. PRP region is exclusively found in mammals and is essential for the Htt interactions with proteins containing tryptophans or Src homology 3 domains. In addition, PRP encodes the polyproline (polyP) region, which interacts with polyQ, increasing the Htt protein stability and solubility. HEAT repeats consist of around 50 amino acids and contains two antiparallel α-helices forming a hairpin, which acts as a scaffold for various protein complexes and mediates inter and intramolecular interactions. Sixteen HEAT repeats organized into four clusters were identified in the Htt protein. Htt protein also has several proteolytic cleavage sites, including proline, glutamic acid, serine, and threonine domains. These domains are found in both Htt and mHtt proteins. Thus, these proteins can be cleaved by caspase 3 at amino acid 513 and 552, caspase 1 at amino acid 572, caspase 2 at amino acid 552, and caspase 6 at position 586. In addition, two calpain cleavage sites are located at amino acid 469 and 536, and the metalloproteinase (MMP)-10 cleaves Htt our mHtt at amino acid 402 [5].
The Htt protein interacts with over 200 other proteins, many of them involved in microtubule-mediated axon traffickings, such as the Huntingtin-associated protein 1 (HAP1), which mediates the interaction between Htt protein with microtubule motor proteins and their co-factors (kinesin, dynactin subunit p150, and dynein). Htt protein also mediates long- and short-range axonal transport and vesicle trafficking. This is because the Htt protein binds to the endocytic pathway-related proteins (clathrin and dynamin), as well as endocytic organelle trafficking proteins (α-adaptin, Hip1, Hip14, HAP40, PACSIN1, SH3GL3/endophilin 3). Htt protein is enriched at synaptic terminals and interacts with cytoskeletal and synaptic vesicle proteins to regulate synaptic activity in neurons. However, by exhibiting a C-terminus containing a nuclear export signal (NES), Htt protein can traffics between cytoplasm and nucleus. In addition, the N17 region also interacts with a nuclear pore protein (TRP), which has nuclear translocation activity. The N-terminal domain also forms an amphipathic alpha-helical membrane-binding domain that reversibly mediates association with the endoplasmic reticulum (ER), endosomes, and autophagic vesicles. Thus, it is not surprising that Htt protein also interacts with various transcription factors and transcriptional regulatory proteins, acting as a positive regulator of brain-derived neurotrophic factor (BDNF) transcription (a protein in which expression levels are found reduced in individuals with HD), stimulating the BDNF vesicular trafficking in neurons.
However, by increasing the number of glutamine residues in poliQ, the CAG trinucleotide expansion, verified in HD, reduces the solubility of mutated huntingtin protein (mHtt), resulting in intracellular aggregates (inclusions) in the brain, particularly in GABAergic medium spiny neurons (MSNs), located within the striatum. This event occurs because the expanded polyQ sequence in mHtt protein undergoes conformational changes to form a Β-pleated sheet prone to aggregation. In addition, the early phases of aggregate formation appear to accelerate the hydrophobic interactions with an amphipathic α-helical structure of N17. Under physiological conditions, proteostasis balances protein synthesis, folding, trafficking, and degradation. The impairment of the proteostasis systems aggravates the aggregation of the misfolded mHtt. In addition, posttranslational modifications influence the mHtt toxicity, aggregation propensity, and intracellular localization. For example, proteolytic cleavage of mHtt generates N-terminal fragments with an increased tendency to aggregate. Furthermore, the mHtt inclusions can block the axonal transport between the cell body and the synaptic cleft and recruit other polyQ-containing proteins, which interact with mHtt, leading to loss of biological function, therefore, cell death. In addition, mHtt also silences the activity of RE1-Silencing Transcription Factor (REST), increasing the binding of REST to RE1/neuron restrictive silencer element, producing transcriptional dysfunction [6, 7].
The mHtt inclusions promote mitochondrial dysfunction, decreasing the activity of mitochondrial respiratory complexes II, III, and IV, which was already verified in
Moreover, the mHtt can be cleaved by caspase 6. The fragments of cleaved mHtt protein bind to several transcription regulators, including the tumor suppressor, p53, thus regulating genes involved in mitochondrial function. Therefore, the mHtt increased the levels of p53, which in turn increased Bax and Puma expression, resulting in mitochondrial dysfunction and neuronal loss. These actions increase the reactive oxygen species (ROS) production, justifying the oxidative damage commonly observed in the plasma of HD patients, HD
Cumulative evidence has also demonstrated that mHtt protein causes a reduction in TORC1, the most potent transcriptional activator of (peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 (PCG-1α) [12, 13, 14]. In addition, the mHtt protein also increases transglutaminase (Tgase) activity, which impairs the transcription of PCG-1α. Thus, mHtt downregulates the expression levels of PCG-1α [14]. The last is recognized as a critical transcriptional coactivator, which interacts with a broad range of transcription factors within a variety of biological processes. In addition, PCG-1α is involved in the regulation of mitochondrial biogenesis, OXPHOS, antioxidant defense, adaptive thermogenesis, and glucose/fatty acid metabolism. Under physiological conditions, the PGC-1α forms heteromeric complexes with nuclear respiratory factors (NRF-1 and NRF-2), and with the nuclear receptors (PPARα, PPARδ, PPARγ and estrogen-related receptor α (ERRα)). These heterodimers regulate the expression of many nuclear-encoded mitochondrial genes, including cytochrome c, complexes I–V, and the mitochondrial transcription factor A (Tfam), as well as antioxidant genes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Thus, the mitochondrial dysfunctions promoted by the mHtt-mediated PCG-1α downregulation lead to an increase in oxidative stress [12, 13, 15].
In addition, the mHtt accumulation in neurons promotes microglial activation, increasing oxidative stress. In addition, microglial cells that express mHtt show significant elevations in nuclear factor kappa B (NF-κB). This elevation occurs because the mHtt interacts with the IκB kinase (IKK) γ subunit, promoting the assembly and activation of the IKK complex (comprised by IKKα and IKKβ subunits). The IKKβ kinase phosphorylates IκBα causes the liberation of NF-κB, promotes the gene expression of the pro-inflammatory cytokine, including interleukin (IL)-6, resulting in neuroinflammation [16, 17]. The neuroinflammatory cytokines produced in response to mHtt protein accumulation leading to the activation of microglial cells considered the brain’s resident immune cells. Under physiological conditions, i.e., in the absence of inflammatory stimulus, microglia are in a surveilling state, being responsible for maintaining synapses and synaptic plasticity. In addition, Microglia also facilitates the growth and development of surrounding neural networks by secreting neurotrophic factors, such as BDNF, nerve growth factor (NGF), and insulin-like growth factor (IGF-1) [18]. Moreover, significant evidence suggests the microglia promotes neurogenesis by phagocytosing apoptotic neural cells, facilitating the migration and differentiation of neural progenitor cells, and secreting soluble factors related to neurogenesis. However, microglia become activated upon detecting inflammatory stimuli, such as the increase in ROS or cytokine production [19]. When activated, microglia can adopt different polarization states, such as M1 and M2. Interestingly, microglia can alternate between these states. For this reason, recently, studies have suggested using M1/M2 terminology to categorize activated microglial cells. M1 microglia exhibit a proinflammatory phenotype, the significant initiators of innate and adaptive immunity in the brain. In addition, these cells elicit a phagocytic function and release cytotoxic factors, including nitric oxide and ROS. M2 microglia also carry out phagocytosis, but contrary to the role of M1 microglia, M2 microglia exhibit an anti-inflammatory phenotype, releasing anti-inflammatory cytokines such as interleukin (IL)-4, IL-13, and transforming growth factor-beta (TGF-β), which suppress inflammatory responses. The continued activation of microglia, stimulated by the inclusions of mHtt, prolonged the production of inflammatory mediators, resulting in chronic inflammation. The last is implicated in further tissue damage, justifying the microglia activation in striatal GABAergic neurons verified by Positron Emission Tomography (PET) in HD patients. Interestingly, studies based on PET also reported the presence of microglia activation in striatal GABAergic neurons in presymptomatic HD gene carriers, suggesting that microglial activation is an early characteristic of HD before symptom onset. However, the activation of microglia increases oxidative stress, resulting in both nuclear and mitochondrial DNA oxidative damages and protein and lipid oxidation. These damages lead to progressive cell death, particularly of MSN’s [20, 21].
Studies based on animal models of HD demonstrate that cell death in the striatum serves as a potent stimulator of progenitor cell proliferation (which are resident into the subventricular zone – SVZ), neuroblast migration, and neurogenesis. This is because, in the transgenic mouse model of HD (in which there is minimal cell loss in the striatum), the SVZ is unaltered, while in rat striatal-lesion models of HD (in which there is a cell loss in the striatum), there is a marked increase in SVZ progenitor cell proliferation and neurogenesis. The SVZ of the lateral ventricle is the resident niche of stem cells. These stem cells give rise to proliferative progenitor cells during brain development, which migrates to the cortex or the basal ganglia, where they differentiate into neurons. SVZ preserves its critical developmental characteristics in the adult brain, responsible for the continuous generation of migrating neuroblasts destined for the olfactory bulb or other areas of cell death in the brain. Thus, the maintenance of SVZ is crucial for neuron replacement along adulthood [22, 23, 24].
Supporting the involvement of SVZ with the physiopathology of HD, several studies revealed that the SVZ of HD patients is enriched in endogenous factors and receptors that actively regulate the cell cycle and the differentiation of precursors, such as the neuropeptide Y. Furthermore, studies already showed a significant increase of GABAA, receptor subunit γ2 (involved in the desensitization of the receptor complex to GABA) in SVZ in HD. GABA is an essential trophic factor for neurons during development. High levels of GABA are found in the normal SVZ and the SVZ of HD patients, suggesting that the SVZ maintains a germinal capacity for proliferation and neurogenesis in response to neurodegenerative cell death in adult life. However, it was proved that, while the Htt protein interacts with cAMP response element-binding protein (CREB) and specificity proetin1 (Sp1), conferring anti-apoptotic action, the mHtt protein triggers a pathogenic cascade involving Sp1 transcription factor activation, which leads to repressor element-1 silencing transcription factor (REST) upregulation, repressing neuronal genes [22, 23, 24].
With the progression of HD, others brain areas, besides the substantia nigra, are subjected to neuronal loss, leading to cognitive and neuropsychiatric dysfunctions. This occurs because the mHtt (as the Htt) is widespread to different brain areas through extracellular vesicles (EVs).The EVs comprise a heterogeneous group of phospholipid bilayer-enveloped particles that are naturally produced and secreted into the extracellular environment by almost all cell types. According to their size, biogenesis, and content, these vesicles are classified as (i) microvesicles, (ii) exosomes, and (iii) apoptotic bodies. Among these vesicles, exosomes are the most investigated. This is because, due to the repertoire of bioactive molecules carried by these vesicles (coding and non-coding RNA, proteins, lipids, and metabolites), the exosomes play an important role in cell-to-cell communication and intercellular signaling, regulating both physiological and pathophysiological processes. Moreover, in the function of their nanosize (30–200 nm), exosomes easily cross the blood-brain barrier [1, 25].
The growing interest in this class of EV has been reflected in the creation of distinct databases that compile data on exosome content, such as Exocarta (http://www.exocarta.org/), EVpedia (http://bigd.big.ac.cn/databasecommons/database/id/4354) and Vesiclepedia (http://microvesicles.org/), which are constantly updated with released studies.
Exosomes are formed by endocytosis and released by exocytosis. During the biogenesis of these vesicles, the inward budding of the plasma membrane results in small intracellular vesicles. These small vesicles fuse, forming early endosomes. The invagination of the early endosome membrane results in the formation of intraluminal vesicles (ILVs) within large multivesicular bodies (MVBs). In contrast, cytoplasmic molecules such as coding and non-coding RNA, proteins, lipids, and metabolites are engulfed and enclosed into the ILV lumen. Along with the maturation of early endosomes to late endosomes, some proteins are directly integrated into the invaginating membrane. However, this process depends on the endosomal sorting complexes required for transport (ESCRTs), which are comprised of four proteins (ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III) that work cooperatively to facilitate the MVB formation, vesicle budding, and protein cargo sorting [1, 25]. The exosomes biogenesis also occurs through an ESCRT-independent pathway mediated by tetraspanins and ceramide-enriched lipid rafts. Tetraspanins are recruited at early steps to endosome membranes before ILV formation, and at least CD9, CD63, CD81, and CD82 are found in endosome and exosome membranes [1, 25].
Ceramides and their derived metabolites are organized in raft-based microdomains that interact with proteins, such as flotillins. The lipid-enriched structures are involved not only in endosomal membrane invagination for ILV formation but also in cargo loading. The selective cargo loading occurs during exosome biogenesis through tetraspanins-dependent and/or ESCRT-dependent mechanisms [1, 25]. Although, the biological cargo of exosomes varies widely according to their cell type of origin, they mainly consist of proteins, nucleic acids (particularly RNA) and lipids. More than 2400 different RNAs and, 4000 proteins were already identified and characterized in exosomes [1, 25].
Due to their endosomal origin, the exosomes are enriched in several proteins engaged in the biogenesis of MVBs, including clathrin, which can bind to hunting protein. Moreover, exosomes contain CD9, CD63, CD81, CD82, CD54, and CD11b tetraspanins, which serve as specific molecules. In addition, the exosomes contain heat shock proteins (HSP90, HSP70, and HSP60), which act as chaperones and play an essential role in cellular responses related to environmental stress. Besides this, exosomes also carry mRNA and a multitude of long non-coding (lnc) RNA and small RNA (particularly miRNA) that can be transferred into recipient cells, inducing cellular responses [1, 25, 26, 27].
The interaction of MVBs with actin and microtubules is essential for their transport to the plasma membrane. The translocation of MVB toward the plasma membrane depends on several molecules via the cytoskeleton. Rab GTPases such as RAB11, RAB27A/B, and RAB35 are mediators of selective sorting of MVB to the plasma membrane and exosome release. The MVBs are decorated with tethering protein complexes, such as HOPS and SNAREs, that mediate the fusion of these vesicles with the plasma membrane, The presence of tetraspanins and lysosomal-associated membrane proteins LAMP1 and LAMP2 in late endosomes also facilitate the fusion of MVB with the plasma membrane [1, 25].
After secretion, the exosomes will dock into the membrane of the target cells and activate signaling events or be internalized through specific receptor-ligand interactions. The transmembrane proteins present in the surface of exosomes (tetraspanins) can be recognized by signaling receptors in the target cells, resulting in activation of transduction pathways and modulation of the intracellular process without entering the target cells. Exosomes can merge with the target cells’ plasma membrane, releasing its cargo directly into the cytosol by a low pH-dependent mechanism. However, the main route for exosome uptake can occur by clathrin-mediated or caveolin-dependent endocytosis, and the presence of lipid rafts in the membrane facilitates the process [1, 25].
After internalization, exosomes are sorted into MVB with two possible fates: (i) to be released again to neighboring cells or (ii) to be degraded after fusion of LE/MVB with lysosomes [1, 25]. The uptake of exosomes by brain cells seems to be cell type-dependent. For instance, neurons and glial cells seem to uptake exosomes by clathrin-mediated endocytosis. Some neurons can also use specific receptors from the SNARE family, such as SNAP25, for exosome uptake. Interestingly, the uptake of exosomes seems to be a selective pathway. Exosomes derived from cortical neurons were primarily internalized by hippocampal neurons, whereas astrocytes and oligodendrocytes took up exosomes released by neuroblastoma cell line N2A. Exosomes derived from oligodendrocytes are mainly internalized by microglia but not by neurons or astrocytes. In addition, the uptake of exosomes was also more active in pre-synaptic regions, which might indicate that these vesicles use constitutive endocytosis processes at these regions for neuronal cell entrance [1, 25].
Initially, exosomes were considered vehicles for the elimination of cellular components. However, current studies have provided evidence that exosomes play multiple physiological roles in the nervous system. Exosomes are released by neural cells, including neurons, astrocytes, microglia, and oligodendrocytes, playing essential physiological roles in neurogenesis, synaptic activity and plasticity, myelination, and protection and regeneration neurons after injury and disease. Thus, it is not surprising that exosomes mediate the pathogenesis of neurodegenerative disorders, such as HD. This is because the misfolded proteins related to these disorders can be selectively integrated into ILVs of MVBs, and subsequently released into the extracellular environment within exosomes [28].
In HD, cumulative evidence has demonstrated that exosomes are implicated in the physiopathology of HD, serving as a vehicle for the expanded polyglutamine tract of HTT RNA and protein (mHtt), as well as mHtt aggregates transport to different brain areas. Supporting this evidence, it was verified that exosomes could deliver expanded trinucleotide repeat RNAs among cells and facilitate the propagation of mHtt protein [29, 30, 31, 32]. It was shown that the injection of fibroblast-derived exosomes from an HD patient into a newborn mouse brain ventricles triggered the manifestation of HD-related behavior and pathology [31]. Moreover, it is known that the Htt protein regulates anterograde and retrograde transport of endocytic vesicles by interacting with several mediators, such as α-adaptin, Hip1, Hip14, HAP1, HAP40, SH3GL3, clathrin, and dynamin [29, 30]. This process is coordinated by the phosphorylation of Htt, which serves as a molecular decision marker for the anterograde or retrograde direction of vesicle transport. Thus, while the Htt promotes axonal BDNF vesicle trafficking, mHtt interacts with HIP1 and dynactin, leading to de-railing of molecular motors from microtubules tracks and cessation of transport [33].
Animal models for HD have been successfully used for more than three decades to identify pathways involved in HD pathology or for preclinical testing of therapeutic strategies. These models are divided into (i) monogenetic and (ii) genetic murine models. However, none of these models can mimic the main feature of HD since no rodent model develops the chorea. For this reason, herein, we summarize the pros and cons of each animal model, considering their utility for preclinical test purposes [34, 35, 36].
Historically, monogenetic models have dominated the field of HD disease. These models are based on the use of toxins that typically induce cell death either by excitotoxic mechanism or by disruption of mitochondrial machinery. Among the excitotoxicity toxins used to obtain murine models for HD are quinolinic acid (QA) and kainic acid (KA). These neurotoxins induce cell death by binding to their cognate receptors, N-methyl-d-aspartic acid (NMDA) and non-NMDA, respectively, on striatal neurons. The QA or KA rat models exhibits motors (hyperkinesia, apomorphine-induced dystonia, and dyskinesia) and cognitive symptoms of HD (visuospatial deficits, procedural memory deficits, and poor memory recall). However, for various reasons, QA became the preferred excitotoxin for use in HD studies. The QA is formed from the metabolism of tryptophan via the kynurenine pathway, which is found in high quantities in the urine of rats that received a diet high in tryptophan. Interestingly, the tryptophan crosses the blood-brain barrier (BBB) using transporters shared by other neutral amino acids. In the brain, tryptophan is taken up by astrocytes, macrophages, microglia, and dendric cells and converted into kynurenine. In the presence of the enzymatic 3-hydroxyanthranilic acid oxygenase, a series of enzymatic reactions converts kynurenine to QA. Thus, the expected level of QA does not cause damage, but only small increases in QA levels cause toxicity. Moreover, it was verified that the administration of QA in the mouse models promotes the upregulation of Htt protein, linking the levels of this neurotoxin with HD pathogenesis. However, the QA is incapable of crossing the BBB. For this reason, the QA has been administrated directly within the brain [37, 38, 39].
Unlike the QA, the mitochondrial toxin 3-nitropropionic acid (3-NP) crosses the BBB and could be systemically administrated through intraperitoneal or subcutaneous injection [40, 41, 42].
The 3-NP is a plant (Indigofera endecapylla) and fungal (Aspergillus flavus, Astragalus, Arthrinium) toxin, which acts as an irreversible inhibitor of succinate dehydrogenase. It inhibits both the Krebs cycle and the mitochondrial complex II of the electron transport chain. The toxin also induces caspase-9 activation, which in turn requires the simultaneous presence of Apaf-1, cytochrome c, and ATP, suggesting that neuronal death may occur in the presence of intense ATP depletion. Moreover, the 3-NP induces oxidative and nitrate stress due to excessive ROS/RNS production and lack of the antioxidant system [40, 43, 44, 45]. Interesting, numerous studies demonstrated that the chronic systemic administration of 3-NP in rats impairs energy metabolism and results in striatal lesions, inducing a spectrum of HD-like pathology in rat striatum. In addition, in 1993, Beal et al. [41] showed that the 3-NP model causes selective striatal lesions characterized by the loss of medium spiny neurons (MSNs) and astroglial proliferation, replicating the histological and neurochemical features of HD. Although, the loss of MSNs in 3-NP rat models causes motor and cognitive symptoms analogous to those verified in HD, this model does not exhibit chorea.
However, the 3-NP model is capable of mimicking both hyperkinetic and hypokinetic symptoms of HD depending on the time course of administration. Thus, while the administration of 3-NP in two individual doses causes hyperkinetic movements analogous to those observed in early to mid-stage HD, the administration of more than four injections of 3-NP causes hypokinetic movements similar to those that appear in late-stage HD [40, 43, 44, 45]. Nevertheless, the response to the 3-NP changes according to the murine (CD1, C57BL/6, BALB/c, Sebster/Swiss and 129sEMS) or rat strain (Fischer, Lewis, and Wistar). In this sense, it is recognized that rats are most vulnerable to the toxic action of 3-NP treatment than mice. Fisher rats are the most susceptible to the 3-NP toxin but display significant variability in response to the toxin due to the difficulty of controlling damage caused by this toxin. In contrast, Lewis rats are less susceptible to 3-NP but respond more stably and consistently to 3-NP in behavioral alterations and lesions. Wistar and Sprague-Dawley rats are also sensitive to the 3-NP, developing lesions and behavioral modifications of extraordinary value for studying possible routes involved in HD and testing new therapeutic strategies. Although, the 3-NP model leads to a (i) massive cell death induced by the toxin, (ii) serving as a helpful model for (ii) analyzing and studying neuroprotective and (iii) neurorestorative therapies for HD patients, (iv) allowing to study the mechanisms involved in HD pathogenesis, including energy deregulations and ROS production, this model does not express the mHtt protein.
The genetic or transgenic animal models emerge as an alternative to nongenetic models since they express the mHtt protein [46, 47]. Transgenic models are divided into (i) those expressing transgenes with a truncated section of human HTT carrying the CAG repeats or full-length human HTT gene, and (ii) those with long CAG repeats replacing mouse Htt. Instability of the CAG repeat has been observed in many of the mouse models and was noted in the first HD model (R6 series). Although, different rodent models have been used to understand the biology of HD or employed in preclinical trials to investigate the therapeutic potential of products candidates to alleviate HD symptoms, they are limited in their ability to provide evidence of the effects of genetic modifiers of disease. In addition, there are many differences among the transgenic rodent models that can lead to different results, especially for preclinical trials.
In this sense, in two independent studies, it was demonstrated that a version of the R6/2 mouse with 90 CAG repeats (R6/2(CAG)90) shows earlier mHtt nuclear aggregation when compared to the R6/2 mouse with 200 CAG repeats (R6/2(CAG)200). Moreover, the R6/2(CAG)90 brains contain nuclear aggregates with a diffuse punctate appearance which remained partly detergent soluble, which correlated with the onset of transcriptional changes. In contrast, the R6/2(CAG)200 brains contain cytoplasmic aggregates that gave larger inclusion bodies related to behavioral changes. These data indicate that CAG length gives different phenotypes [48, 49, 50].
Several models encoding glutamine but using a mixed CAACAG rather than a pure CAG tract were developed to prevent germline and somatic expansion of CAG trinucleotide. An example of these models is the BACHD models with 97 glutamines encoded by a diverse CAACAG tract. These mice have five copies of the transgene integrated into their genome and express BACHD HTT, an estimated three-fold level of the transcript, and 1.5 to 2-fold protein level (mHtt).
BACHD rats show string impairment in muscle endurance at 2 months of age. Altered circadian rhythmic and locomotor activity are also observed in these animals [51, 52, 53]. However, the BACHD model is not commercially available, difficult to access this model.
When discovered, stem cells—therapeutic cells gain exceptional attention due to their capacity to produce precursors and differentiated cells. Propose, therefore, was to use stem cells in tissue regeneration [26, 27]. Stem cells showed differentiation potential
MSC secretes a large number of biologically active molecules, growth factors, hormones, interleukins, etc. [29]. These biomolecules can be found in free form or contained in exosomes, which are recognized as a key component in paracrine regulation [1, 25]. These molecules provide beneficial effects on injured tissues. For example, they induce angiogenesis and tissue regeneration and inhibit fibrosis, apoptosis, and inflammation [30, 31, 32]. In addition, which is essential for HD disease, MSCs and MSC’s secretomes provide neurogenic, neuroprotective, and synaptogenic effects [33]. They improve the abnormal dopamine transmission and inflammatory reaction in the transgenic HD model [34]. Animal models showed that they produce factors protecting retinal ganglion cells against glutamate excitotoxicity, neurotrophins expressed by MSCs inhibit pro-inflammatory cytokine secretion, MSCs fight oxidative stress and others [35, 36]. Due to the characteristics above, MSCs called medicinal signaling cells or simply therapeutic cells [37].
Medicinal signaling cells (MSC) have been used in a variety of preclinical studies, which were focused on behavioral and memory outcomes, reduction of brain damage and minimization of striatal degeneration. “Native” MSC isolated from different adult tissues such as bone marrow, adipose tissue and umbilical cord were used in these studies. Due to their ability to adhere to plastic, MSC can be easily isolated and expanded
Stem cell-based therapies are important to reconstruct damaged brain areas in HD patients. These therapies have a dual role: stem cell paracrine action, stimulating local cell survival, and brain tissue regeneration through the production of new neurons from the intrinsic and likely from donor stem cells. Initially, preclinical studies were mainly focused on the neuroprotective function of MSC. Since these cells express a variety of neurotrophins and in particular brain-derived neurotrophic factor (BDNF), which is implicated in the survival of striatal neurons. BDNF expression is reduced in Huntington’s disease (HD) contributing to striatal neurodegeneration.
Initially, preclinical studies mainly discussed the neuroprotective function of MSC. Since these cells express BDNF, which is implicated in the survival of striatal neurons, its expression is reduced in Huntington’s disease (HD) contributing to striatal neurodegeneration. The regenerative approaches of MSC potentially can cause the (i) promotion of endogenous neuronal growth; (ii) amelioration of the synaptic connection from damaged neurons; (iii) decrease of apoptosis of endogenous neurons; (iv) reduction of the levels of free radicals; (v) immunomodulation. Our group widely discussed these MSC functions in animal models in previous publications (Figure 1) [43, 44].
Schematic representation of the paracrine and cellular mechanism of MSC action observed in pre-clinical studies in Huntington and other degenerative diseases. Paracrine action mainly includes neurotrophins and other soluble factors, including growth factors, small molecules, and cytokines, providing signals to cells and resulting in different cell actions such as survival, proliferation, and differentiation. The paracrine factors are secreted directly into the intercellular matrix or included in extracellular vesicles (exosomes) before secretion. The cellular effect includes mitochondria transfer and MSC mediated autophagy. MSC acting by paracrine and cellular mechanisms showed significant therapeutic potential.
Furthermore, MSC can transfer larger molecules and even organelles, therefore, their use as delivery vehicles for therapeutic RNA inhibition was suggested [45]. MSC can transfer larger molecules and even organelles; therefore, suggesting their use as delivery vehicles for therapeutic RNA inhibition [45].
In addition, more recent findings suggest the potential therapeutic effect of MSC on different pathophysiological aspects of HD, such as (i) mitochondrial dysfunction; (ii) transcriptional dysregulation [49, 50]; (iii) altered axonal transport of critical factors [51, 52]; (iv) disrupted calcium signaling [53, 54]; (v) abnormal protein interactions [55]; (vi) impaired autophagy [56, 57]. However, here we will focus our review on HD mitochondrial dysfunction and MSC mitochondria transfer.
Figure 1 combines the well-known paracrine mechanism of MSC action and a novel cellular mechanism mediated by mitochondria transfer and autophagy. Both, paracrine and cellular, mechanisms provide clinical, cellular and molecular benefits in HD [43, 44, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59]. The complex mechanisms of MSC action and her multi-target orientation are the unique biological tool that could act on multiple pathophysiological aspects of HD cited above.
Mitochondria roles in neurons differ from only a cell power source. Mitochondria are also dynamic organelles that fragment and fuse to achieve a maximal bioenergetics action. They are transported along microtubules, regulated intracellular calcium homeostasis through the interaction with the endoplasmic reticulum. In addition, they produce free radicals and participate in cell apoptosis [60]. These activities have been demonstrated to be changed in HD, potentially contributing to neuronal dysfunction in early pre-symptomatic HD phases. Thus, a polyglutamine-expansion disorder that primarily affects the striatum and the cerebral cortex has been described as mitochondrial dysfunction, an early pathological mechanism presenting selective HD neurodegeneration [61, 62]. One of the hallmarks of HD is an altered mitochondrial morphology that can be seen in different cell types and neurons, which are characterized by increased mitochondrial fragmentation [63]. The cells with altered mitochondrial morphology in HD cells showed a decrease in electron transport chain activity, oxygen consumption, Ca2+ buffering, and decreased ATP and NAD+ production [64]. It has been suggested that mitochondrial abnormalities can significantly affect MSNs due to the high-energy demand of this neuronal subtype [65]. Therefore, the mitochondria are a central regulatory organelle in HD-affected neurons.
In addition, mitochondria act as a reservoir for pro-apoptotic factors, thus regulating cell death. The mitochondrial permeability transition pore (mPTP) is opened due to mitochondrial dysfunction, Ca2+ overload, and accumulation of reactive oxygen species (ROS). The transition pore opening initiates the intrinsic apoptotic pathway, which is connected with the mitochondrial outer membrane permeabilization, awakening cytochrome c release, and activation of caspase-3 [66, 67]. Bcl-2 inhibits the activation of proapoptotic factors such as Bcl-2-associated X protein (Bax) and Bcl-2-associated K protein (Bak), thus suppressing the release of cytochrome c from mitochondria. The Bax/Bcl-2 ratio imbalance often occurs during the process of apoptosis [68]. MSC mitochondrial transfer through regulation of the balance of Bax/Bcl-2 and reduction of the expression of caspase-3 can reduce apoptosis levels and promote cell viability in recipient cells [69, 70].
Recent studies have demonstrated that MSCs have the potential to transfer the defective mitochondria between MSCs and aging cells [71]. For the first time, the MSC mitochondria transfer was shown in A549 cells with mtDNA deletions after their co-culture with human MSCs. This work demonstrated the recovery of function by mitochondrial activities such as increased oxygen consumption, membrane potential, and intracellular ATP levels [72].
It is worth mentioning that the transfer of dysfunctional mitochondria from damaged cells to MSC also can occur. Gozzelino et al. showed that mitochondria released from damaged cardiomyocytes or endothelial cells could be “swallowed” by MSCs. This event rigger increases the expression of Heme oxygenase-1 (HO-1), a protein that protects against programmed cell death, and increases mitochondria in MSCs, which in turn induces an adaptive reparative response [73, 74].
Fluorescence microscopy studies revealed MSC mitochondria transfer in astrocytes and neuron-like pheochromocytoma cells. MSC mitochondria transfer to astrocytes was more efficient when the astrocytes were subjected to ischemic damage associated with elevated ROS levels. The ROS accumulation in normal aging or disease leads to increasing the rate of mitophagy and decreasing the level of mitochondrial biogenesis, which reduces mitochondrial mass [75]. Such mitochondria transport re-established the bioenergetics of the recipient cells and stimulated their proliferation. Furthermore, the authors showed that MSCs mitochondria transferability may be enhanced by upregulation of Miro1 (adaptor protein participating in mitochondria moving along microtubules [76] therefore, this study showed that mitochondrial impairment in differentiated cells can be restored after MSC healthy mitochondria transfer and this approach may serve as a promising treatment for neurological diseases [77].
Tissue injury or degeneration is usually followed by inflammation, which is a driving force for mitochondrial transfer. In HD, massive neuroinflammation in the striatum and caudate nucleus are already present before patients develop any symptoms [21, 78, 79]. The therapeutic effects of MSC are mediated mainly by its secretome/exosomes since in response to a combination of molecules present in the inflamed microenvironment, these cells undergo a process activation or “licensing,” acquiring an anti-inflammatory phenotype and producing large amounts of immunomodulation factors, growth factors and specific chemoattractants, being able to modulate significantly innate and adaptive immune cells [38, 80].
The MSCs secreted cytokines that immunomodulate various immune cells, such as T cells, B cells, natural killer cells, and macrophages [81]. Recent studies demonstrated that between MSCs and immune cells MSC mitochondrial transfer can occur, such influencing the functions of the immune cells. Jackson et al. showed MSC mitochondria transfer occurs in an acute respiratory distress syndrome (ARDS) model. MSC provides mitochondria to host macrophages, thus enhancing the phagocytic capacity and bioenergetics of macrophages. This MSC mitochondria transfer leads to improved clearance of pathogenic bacteria [82]. Using the same model Morrison et al. showed that MSC exosomes mediated transfer of mitochondria, which can induce monocyte-derived macrophages to differentiate to an M2 phenotype with a high phagocytic capacity [58]. In addition, MSC mitochondria transfer regulates T cell differentiation. Some authors reported that when healthy donor-derived bone marrow-derived MSC (BMMSC) is cocultured with primary Th17 effector cells, the mitochondrial transfer occurs, increasing respiration in recipient Th17 cells [59].
HD demonstrates typical cellular and molecular features of inflammation, such as cytokine expression and microglia activation. However, no immune cell infiltration from the bloodstream was observed [83, 84]. Nevertheless, HD is characterized by a chronic increase of systemic pro-inflammatory cytokine production. Microglia and astrocytes are non-neuronal cells in the brain that participate in tissue homeostasis and support neuronal function. Under pathologic conditions, these cells become ‘activated.’ They start to produce numerous mediators promoting inflammation. These cells change their morphology and, can divide, thus increasing cell numbers, an event named ‘gliosis.’ Recent studies suggest that cell-autonomous pro-inflammatory activation of microglia occurs due to the expression of mutant HTT, thus contributing to the progression of HD pathogenesis [21].
MSC’s metabolic state is characterized by the balance between the intrinsic necessities of the cell and limitations imposed by extrinsic conditions. Under pathogenic conditions or inflammation, MSCs respond to reactive oxygen species (ROS), damage-associated molecular patterns (DAMPs), damaged mitochondria, and mitochondrial products, thus transferring their mitochondria to damaged cells. MSC therapies can protect the potentially damaged cells by regulating cellular metabolism in injured tissues, modulating ROS and endogenous MSCs.
Furthermore, to treat such complex diseases like Huntington’s, we should develop new complex therapies acting on multiple targets. MSC, due to the wide range de therapeutic molecules they produced and the different mechanisms they used to fight the disease, these cells are a good candidate for the new class of such therapeutics.
For a long, it was considered that the therapeutic effects of the stem cells were associated with the replacement of dead cells [73, 74]. However, in a model of kidney injury caused by the injection of toxic doses of glycerol, it was verified that transplanted stem cells remain in the injury site for up few days and, subsequently, are not found in the tissue [73, 75, 76]. These data provide evidence that the therapeutic potential of MSCs is mediated by trophic factors naturally produced and secreted by these cells in an accessible form or into EVs [1]. However, whereas the bioactive molecules present in the extracellular medium are subjected to rapid hydrolysis and oxidative effects, the biomolecules present in EVs are more stable [73]. For this reason, the EVs (particularly exosomes) have been biotechnology explored in a novel therapeutic approach known as cell-free therapy [26, 77, 78].
Cell-free therapy possesses different advantages when compared with cell-based treatment. Among these advantages are: [1] EVs can be easily prepared, stored for a relatively long period without any toxic cry preservative such as dimethylsulphoxide (DMSO) and transported; [2] therapeutic application of exosomes have been demonstrated to be well tolerated; [3] the use of EVs instead of whole cells avoids possible complications associated with pulmonary embolism after intravenous infusion of MSCs; [4] avoids the risk of unlimited cell growth and tumor formation since EVs are not dividing; [5] exosomes from MSCs, and epithelial cells do not induce toxicity when repeatedly injected; [6] EV may be isolated from unmodified or genetically modified human stem cells; [7] evaluation of culture medium for safety and efficacy is much simpler and analogous to conventional pharmaceutical agents [1, 73, 79, 80, 81, 82]. Further, the cell-free therapy allows biotechnologically exploring the use of the culture medium, which is generally discarded as a byproduct of the in vitro expansion of MSCs. This is because this culture medium—also termed conditioned medium (CM) [79]—is an essential source of bioactive molecules, which can find in an accessible form or an extracellular vesicle (EVs) [1].
Although, different strategies have been successfully used to isolate exosomes, they represent the main obstacle to the therapeutic application of EV since these procedures are time-consuming and generally provide few quantities of EVs [1, 73]. However, novel methodologies have been proposed to solve these problems. Based on this, we aimed to summarize the pros and cons of each available method for isolating exosomes.
Ultracentrifugation (UC) and commercial kit rooted in polymer-based precipitation are the most well-established and standard methods used for isolating exosomes [74], being adopted as a strategy in about 81% of researches [78]. Ultracentrifugation-based methods can be divided into two major types of techniques according to the separation mechanism: (i) differential ultracentrifugation and (ii) density gradient ultracentrifugation [78]. For both methods, death cells, cellular debris, and large EVs (>200 nm) are separated using low centrifugal forces (300–2000 ×
Another strategy commonly employed to isolate exosomes is coprecipitation. This method uses polymers, such as polyethylene glycol (PEG) 6000 or 8000, which can coprecipitate with hydrophobic proteins and lipid molecules present in exosome membranes [78]. Although, most simple and less expensive than the methods based on ultracentrifugation, the isolation using coprecipitation is not scalable, limiting its use for therapeutic purposes. Moreover, this technique requires sample incubation with the polymers for a long time (generally 12–16 h) [1].
The differential expression of specific surface biomarkers, such as CD9, CD63, and CD83, also provides an excellent opportunity to develop immunoaffinity-capture-based techniques for exosomes isolation using modified magnetic beads or microchannels surfaces with specific antibodies [1, 78]. Although, this technique allows isolating only exosomes, it works with few volumes, limiting its use for therapeutic purposes, which require scalable methods. Moreover, this method generally requires a pre-enrichment step, which is commonly performed using commercial kits based on coprecipitation, resulting in PEG contamination [1].
Another strategy used to isolate exosomes is the size-based isolation technique. This technique can be based on sequential filtration, size-exclusion chromatography (SEC), and size-dependent microfluids. These methods allow isolating the EVs according to their size [78]. EVs are separated using membrane filters with different size or molecular weight exclusion limits in sequential filtration. First, the CM is filtered using a 0.22 μm membrane filter. Then, proteins with a 500 kDa molecular weight are purified using a dialysis bag. Finally, the samples are filtered with a 100 nm membrane filter [78]. The SEC is based on particle size filtration through a porous stationary phase composed of spherical gel beads with pores of specific size [78]. Large particles are eluted when the sample passes through the stationary phase, whereas small particles pass through the pores [78]. The size-dependent microfluidics uses a viscoelastic microfluidics device, composed of a microchannel, two inlets, and three inlets, to fractionate exosomes from other types of EVs [78]. These techniques are faster than those based on ultracentrifugation and do not require special equipment. Moreover, they avoid PEG contamination, frequently observed in coprecipitation-based methods. However, the size-based isolation techniques are relatively expensive and cannot separate exosomes from other EVs, requiring additional steps for exosome purification [1].
Due to their ability to cross the blood-brain barrier and biocompatibility, exosomes are promising therapeutic drug carriers into the CNS. In HD, exosomes are exceptionally efficient in delivering specific microRNAs (miRs), short non-coding RNAs of about 22 nucleotides that regulate gene expression by suppressing the translation of mRNA, which are found deregulated in HD patients.
In this sense, several miRs had already been identified as deregulated in HD, including the miR-124, which was found downregulated in HD patients [85]. The decreased expression of miR-124 increases the levels of its target gene (REST), which acts as a repressor of BDNF [85]. By contrast, the expression of miR-124 induces adult neurogenesis in the subventricular zone (SVZ) and regulates the cell cycle in striatal neurons. Considering that the HD striatum exhibits decreased neurogenesis, which leads to brain atrophy, it was hypothesized that the delivery of miR-124 may be a feasible way to induce neural regeneration. However, naked miRs are vulnerable to degradation.
In this regard, exosomes emerge as candidates for the miR-124 delivery to recipient cells. Based on this, Lee et al. [85] injected exosomes derived from HEK 293 cells overexpressing miR-124 within (Exo-124) the striatum of 6-week-old R6/2 transgenic mice. Using ex vivo imaging, the authors demonstrated the presence and maintenance of the exosomes within the striatum even after one week later the Exo-124 administration. Furthermore, it was verified that Exo-124-treated R6/2 mice exhibited slightly higher levels of miR-124 when compared to the non-treated mice (control). However, no statistically significant differences between the treated and control mice were reported. By contrast, the Exo-124-treated R6/2 mice exhibited lower levels of REST protein concerning the control. Although, the study had provided a proof of concept for exosome-based delivery of miRNAs to the brain, the therapeutic efficacy of Exo-124 was modest, suggesting the need to increase the dose of miRNAs packed in the exosomes or to combine this miRNA with other candidate miRNAs such as miR-9, miR-22, miR-125b, miR-146a, miR-150, and miR-214.
In this sense, the exosomes derived from MSCs can be considered an important source of these miRs and other mRNAs and proteins deregulated in HD physiopathology. Supporting this, Lee et al. [86] showed that exosomes derived from an adipose-derived stem cell (ASC-exo) decreased mHtt aggregates in R6/2 mice-derived neuronal cells through the upregulation of PGC-1, phospho-CREB.
In this review, we demonstrated that Huntington’s disease is devastating and affects brain cells and the organism as a whole. Although, the main cause of HD patients’ death is medium spiny neurons, many specific events occur at presymptomatic and symptomatic HD phases. Currently, Huntington’s chorea is in the focus of pharmaceutical companies, producing drugs able to combat this HD symptom. However, these drugs are always not possible to delay the disease and present moderate to severe side effects.
In contrast to conventional drugs, MSC is safe, and they did not present any side effects as shown in multiple clinical trials. MSC showed therapeutic potential distinct from, for example, small molecules and biologics. Cells are deposited multiple drugs, they can sense diverse signals, migrate to specific sites in the body, make decisions, and carry out complex responses inside one specific tissue environment.
Our knowledge about the biology and therapeutic potential of these cells is still minimal; however, as demonstrated by scientific literature, these cells and their derivatives as exosomes and mitochondria have tremendous therapeutic potential. Pre-clinical studies provided evidence about the paracrine effect of these cells’ such as regenerative, anti-apoptotic, anti-fibrotic anti-inflammatory, immunosuppressive, immunomodulatory, and angiogenic.
More recently, the potential effect of MSC against different pathophysiological aspects of HD, such as mitochondrial dysfunction; transcriptional dysregulation; altered axonal transport of critical factors; disrupted calcium signaling; abnormal protein interactions, and impaired autophagy, has been demonstrated.
This review tries to provide insight into cellular and cell-free technologies from the exact cellular origin. These cell and cell-free products may share similar features and present specific characteristics, as demonstrated for MSC, exosomes, and mitochondria. We tried to clarify that these products aim at different cellular targets or molecular pathways involved in Huntington’s disease. Therefore, we should study how to use these new therapeutics, which can delay or even stop neurodegenerative devasting diseases.
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Yet, little is known about the HRQoL of Turkish and Polish migrants and German natives.",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Johanna Buchcik, Joachim Westenhöfer, Mick Fleming and Colin R.\nMartin",authors:[{id:"192396",title:"Dr.",name:"Johanna",middleName:null,surname:"Buchcik",slug:"johanna-buchcik",fullName:"Johanna Buchcik"},{id:"193514",title:"Prof.",name:"Joachim",middleName:null,surname:"Westenhöfer",slug:"joachim-westenhofer",fullName:"Joachim Westenhöfer"},{id:"193515",title:"Prof.",name:"Mick",middleName:null,surname:"Fleming",slug:"mick-fleming",fullName:"Mick Fleming"},{id:"193516",title:"Prof.",name:"Colin R.",middleName:null,surname:"Martin",slug:"colin-r.-martin",fullName:"Colin R. Martin"}]},{id:"53700",doi:"10.5772/67013",title:"Migration and Health from a Public Health Perspective",slug:"migration-and-health-from-a-public-health-perspective",totalDownloads:2359,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"One of the main dimensions related to migration is that of health; this correlation is dynamic by nature and complex. Health is strongly related to the social determinants of health (job, income, education, and housing). When not properly supported by appropriate inter-sectoral policies, migration can expose the most vulnerable socioeconomic groups to significant problems. The protection of the health of migrants is an important investment of the public health because it promises benefits to both migrant population and natives. An essential aspect is to properly analyze the health needs of ethnic minorities. Both quantitative and qualitative research is necessary, and the involvement of the target communities is important. Another important aspect is the education and training of social and health workers involved in the care of migrants (with a multidisciplinary teamwork and “transcultural” approach), and the organization of services that can effectively be used. Finally, it is also essential to carry out an evaluation of health outcomes of the migrant population and the impact of adopted health policies. Protecting the health of ethnic minorities is both a challenge for governments and a test of the quality of their health systems.",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Maurizio Marceca",authors:[{id:"192600",title:"Prof.",name:"Maurizio",middleName:null,surname:"Marceca",slug:"maurizio-marceca",fullName:"Maurizio Marceca"}]},{id:"53657",doi:"10.5772/66827",title:"Asians as Model Minorities: A Myth or Reality among Scientists and Engineers in Academia",slug:"asians-as-model-minorities-a-myth-or-reality-among-scientists-and-engineers-in-academia",totalDownloads:1510,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"Asians from China, India, South Korea, and Taiwan constitute the largest non‐White group in academic science and engineering (S&E). Most of the studies in relation to race/ethnicity combine Asians into one category whether they are immigrants (foreign born) or US citizens. Research has suggested that job satisfaction differs with the type of citizenship status held by faculty members. However, what studies fail to notice is that Asian faculty members who are either born in the United States or are naturalized might experience very different levels of attitudes and satisfaction toward their job when compared with Asian faculty members who are foreign born and on temporary visa status, impacting retention. Do institutions recognize the differences between these two groups, or are Asian faculty members considered a “model minority” group and “problem‐free?” This is the question that this study aims to examine. Given the growing competition in S&E globally, matters pertaining to faculty members’ satisfaction, retention, and persistence will take a front seat among policy makers and university administrators. Data for this study come from the National Science Foundation’s Survey of Doctorate Recipients (SDR).",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Meghna Sabharwal",authors:[{id:"192631",title:"Associate Prof.",name:"Meghna",middleName:null,surname:"Sabharwal",slug:"meghna-sabharwal",fullName:"Meghna Sabharwal"}]},{id:"53671",doi:"10.5772/67004",title:"The New Actors of International Migration: A Comparative Analysis of Foreign Students’ Experiences in a Medium-Sized City in Turkey",slug:"the-new-actors-of-international-migration-a-comparative-analysis-of-foreign-students-experiences-in-",totalDownloads:1241,totalCrossrefCites:0,totalDimensionsCites:4,abstract:"International or foreign student migration is one of the topics that started to become a hot topic in many different countries because of various aspects. Lately, Turkey, especially in terms of higher education, can be seen as a country that sends students to study abroad but also attracts foreign students. With regard to Adnan Menderes University which is located in a medium‐sized city (Aydın), the main focus of this study is based on experiences of foreign students regarding prejudice, discrimination and racism. In addition to this, the topics such as to what extent are foreign students having difficulty to adapt to the life in Turkey, to what extent are the students satisfied with their lives in the country, in what way could foreign students who currently study in Turkey help to increase the foreign student population or sustain the student migration were examined. In this context, six different categories, such as students from Africa, Asia, South Caucasia, Middle East, Europe/Balkans and Europe/Other, were created. Surveys were applied to participants of the study group in line with a quantitative research scope.",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Serdar Ünal",authors:[{id:"192402",title:"Dr.",name:"Serdar",middleName:null,surname:"Ünal",slug:"serdar-unal",fullName:"Serdar Ünal"}]},{id:"53486",doi:"10.5772/66824",title:"Immigration and Food Insecurity: The Canadian Experience—A Literature Review",slug:"immigration-and-food-insecurity-the-canadian-experience-a-literature-review",totalDownloads:2559,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Canada is a popular destination for immigrants and integration of newcomers is an important strategy for its demographic growth and economic development. Food insecurity disproportionately affects newcomers in Canada; unfortunately, they occupy the lower end of the socio‐economic spectrum and thus adding to the burden of socio‐cultural challenges they are already facing. The high level of food insecurity contributes to poor diet quality and the rise in overweight and other chronic health conditions and therefore to the loss of healthy immigrant status. Indeed, statistical evidence, mainly of the overall Canadian population, demonstrates that individuals living in food‐insecure households have higher rates of self‐reported poor health and chronic health conditions. Therefore, understanding and properly addressing the factors associated with food insecurity among Canadian immigrants is crucial for an adequate integration of immigrants. This chapter suggests that an adequate and appropriate understanding of food security for Canadian immigrant populations requires consideration of a cultural perspective in addition to the traditional individual, household and community levels and the development of measurement tools to capture this cultural dimension. It is proposed the concept of cultural food insecurity encompasses the four usual dimensions (availability, accessibility, utilization, and stability) and a newly proposed fifth cultural dimension. Future research should aim at validating the relevance of this cultural perspective as a fifth pillar for food security and developing measurement tools to assess it.",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Diana Tarraf, Dia Sanou and Isabelle Giroux",authors:[{id:"192842",title:"M.Sc.",name:"Diana",middleName:null,surname:"Tarraf",slug:"diana-tarraf",fullName:"Diana Tarraf"},{id:"193533",title:"Dr.",name:"Dia",middleName:null,surname:"Sanou",slug:"dia-sanou",fullName:"Dia Sanou"},{id:"193603",title:"Dr.",name:"Isabelle",middleName:null,surname:"Giroux",slug:"isabelle-giroux",fullName:"Isabelle Giroux"}]}],mostDownloadedChaptersLast30Days:[{id:"53486",title:"Immigration and Food Insecurity: The Canadian Experience—A Literature Review",slug:"immigration-and-food-insecurity-the-canadian-experience-a-literature-review",totalDownloads:2562,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Canada is a popular destination for immigrants and integration of newcomers is an important strategy for its demographic growth and economic development. Food insecurity disproportionately affects newcomers in Canada; unfortunately, they occupy the lower end of the socio‐economic spectrum and thus adding to the burden of socio‐cultural challenges they are already facing. The high level of food insecurity contributes to poor diet quality and the rise in overweight and other chronic health conditions and therefore to the loss of healthy immigrant status. Indeed, statistical evidence, mainly of the overall Canadian population, demonstrates that individuals living in food‐insecure households have higher rates of self‐reported poor health and chronic health conditions. Therefore, understanding and properly addressing the factors associated with food insecurity among Canadian immigrants is crucial for an adequate integration of immigrants. This chapter suggests that an adequate and appropriate understanding of food security for Canadian immigrant populations requires consideration of a cultural perspective in addition to the traditional individual, household and community levels and the development of measurement tools to capture this cultural dimension. It is proposed the concept of cultural food insecurity encompasses the four usual dimensions (availability, accessibility, utilization, and stability) and a newly proposed fifth cultural dimension. Future research should aim at validating the relevance of this cultural perspective as a fifth pillar for food security and developing measurement tools to assess it.",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Diana Tarraf, Dia Sanou and Isabelle Giroux",authors:[{id:"192842",title:"M.Sc.",name:"Diana",middleName:null,surname:"Tarraf",slug:"diana-tarraf",fullName:"Diana Tarraf"},{id:"193533",title:"Dr.",name:"Dia",middleName:null,surname:"Sanou",slug:"dia-sanou",fullName:"Dia Sanou"},{id:"193603",title:"Dr.",name:"Isabelle",middleName:null,surname:"Giroux",slug:"isabelle-giroux",fullName:"Isabelle Giroux"}]},{id:"53470",title:"Sociocultural Models of Second-Language Learning of Young Immigrants in Canada",slug:"sociocultural-models-of-second-language-learning-of-young-immigrants-in-canada",totalDownloads:1619,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The most significant challenge for the minority immigrant is learning a new language. They arrive in a new culture and community hoping to master English quickly in order to achieve their academic and career goals. However, many immigrants have mentioned general barriers resulting from being unable to communicate with peers outside their cultural and linguistic group. Recent research has identified several cognitive variables such as vocabulary, reading aloud, and grammatical judgment related to second-language learning in immigrants; however, little attention was given to sociocultural factors such as acculturation, motivation, and cultural learning because learning a language is a necessary aspect of being socialized into a particular culture. This chapter reviews research of sociocultural models in relation to second-language learning of immigrant youth in Canada. We address this paradigm for research by incorporating both acculturation and sociolinguistic approaches, as well as more traditional cognitive-linguistic approaches, to models of second-language learning in immigrants.",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Fanli Jia, Alexandra Gottardo and Aline Ferreira",authors:[{id:"192435",title:"Dr.",name:"Fanli",middleName:null,surname:"Jia",slug:"fanli-jia",fullName:"Fanli Jia"},{id:"194425",title:"Dr.",name:"Alexandra",middleName:null,surname:"Gottardo",slug:"alexandra-gottardo",fullName:"Alexandra Gottardo"},{id:"194656",title:"Dr.",name:"Aline",middleName:null,surname:"Ferreira",slug:"aline-ferreira",fullName:"Aline Ferreira"}]},{id:"53700",title:"Migration and Health from a Public Health Perspective",slug:"migration-and-health-from-a-public-health-perspective",totalDownloads:2366,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"One of the main dimensions related to migration is that of health; this correlation is dynamic by nature and complex. Health is strongly related to the social determinants of health (job, income, education, and housing). When not properly supported by appropriate inter-sectoral policies, migration can expose the most vulnerable socioeconomic groups to significant problems. The protection of the health of migrants is an important investment of the public health because it promises benefits to both migrant population and natives. An essential aspect is to properly analyze the health needs of ethnic minorities. Both quantitative and qualitative research is necessary, and the involvement of the target communities is important. Another important aspect is the education and training of social and health workers involved in the care of migrants (with a multidisciplinary teamwork and “transcultural” approach), and the organization of services that can effectively be used. Finally, it is also essential to carry out an evaluation of health outcomes of the migrant population and the impact of adopted health policies. Protecting the health of ethnic minorities is both a challenge for governments and a test of the quality of their health systems.",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Maurizio Marceca",authors:[{id:"192600",title:"Prof.",name:"Maurizio",middleName:null,surname:"Marceca",slug:"maurizio-marceca",fullName:"Maurizio Marceca"}]},{id:"53859",title:"Introductory Chapter: People's Movements in the 21st Century",slug:"introductory-chapter-people-s-movements-in-the-21st-century",totalDownloads:1478,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Ingrid Muenstermann",authors:[{id:"77112",title:"Dr.",name:"Ingrid",middleName:null,surname:"Muenstermann",slug:"ingrid-muenstermann",fullName:"Ingrid Muenstermann"}]},{id:"53701",title:"The Immigrant Experience in V.S. Naipaul's The Enigma of Arrival and Z. Smith's White Teeth: An Exploration of Homi Bhabha's Postcolonial Theory",slug:"the-immigrant-experience-in-v-s-naipaul-s-the-enigma-of-arrival-and-z-smith-s-white-teeth-an-explora",totalDownloads:2073,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"V.S. Naipaul and Z. Smith, prominent postcolonial authors, reflect the condition of the immigrants suffering from cultural shock, hybridity, fragmentation and mimicry in the postcolonial Western societies in their novels, The Enigma of Arrival and White Teeth. The former portrays the desperate condition of an author doing his best to create his work in the post‐war West, in London and New York, trying to overcome his hybridity and adaptation problems due to his cultural background, and the latter sheds light on the cultural distress of two families from Bangladesh, immigrating to London, by stressing the conflicts between the Westerners and the Easterners and between the first and the second generations of immigrants. Thus, these two novels highlight the immigrant experience illustrating the impact of power relations between the former colonized and the former colonizer upon their relationship in the postcolonial era. In this study, the problems of immigrants in the post‐war West in these novels will be analysed in the light of Homi Bhabha's postcolonial theory, which puts forward such concepts as hybridity, mimicry, ambivalence, cultural differentiation and otherness. In this regard, Bhabha's theory will be adapted into these novels to identify cultural problems of immigrants in these works.",book:{id:"5598",slug:"people-s-movements-in-the-21st-century-risks-challenges-and-benefits",title:"People's Movements in the 21st Century",fullTitle:"People's Movements in the 21st Century - Risks, Challenges and Benefits"},signatures:"Berna Köseoğlu",authors:[{id:"148215",title:"Dr.",name:"Berna",middleName:null,surname:"Köseoğlu",slug:"berna-koseoglu",fullName:"Berna Köseoğlu"}]}],onlineFirstChaptersFilter:{topicId:"1325",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:290,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. 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He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:249,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"11",type:"subseries",title:"Cell Physiology",keywords:"Neurodevelopment and Neurodevelopmental Disease, Free Radicals, Tumor Metastasis, Antioxidants, Essential Fatty Acids, Melatonin, Lipid Peroxidation Products and Aging Physiology",scope:"\r\n\tThe integration of tissues and organs throughout the mammalian body, as well as the expression, structure, and function of molecular and cellular components, is essential for modern physiology. 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This includes, but is not limited to: single-neuron modeling, sensory processing, motor control, memory, and synaptic plasticity, attention, identification, categorization, discrimination, learning, development, axonal patterning, guidance, neural architecture, behaviors, and dynamics of networks, cognition and the neuroscientific basis of consciousness. 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Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization"},{id:"26",title:"Machine Learning and Data Mining",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence"},{id:"27",title:"Multi-Agent Systems",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. 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We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"\r\n\tScientists have long researched to understand the environment and man’s place in it. 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\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
\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.
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",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"