Fold increase C/EBP alpha and G-CSFR mRNA expression (analyzed in triplicates) in gene expression in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
\\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:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5884",leadTitle:null,fullTitle:"Unraveling the Safety Profile of Nanoscale Particles and Materials - From Biomedical to Environmental Applications",title:"Unraveling the Safety Profile of Nanoscale Particles and Materials",subtitle:"From Biomedical to Environmental Applications",reviewType:"peer-reviewed",abstract:"As nanomaterials become increasingly present in our daily lives, pertinent questions regarding their safety arise. Nanomaterial risk assessment, as in other areas, directs much of the effort worldwide in defining guidelines that may be translated into national or international directives. Nanomaterials encompass different entities, from nanoparticles to nanostructured materials, with specific effects over cells, tissues, organisms and ecosystems depending on their biophysical characteristics. Such interactions will directly affect the impact of novel nanotechnologies. This book aims to provide the reader with a comprehensive overview of the current state of the art in nanotoxicology, featuring the most important developments and critical issues regarding the use of and exposure to nanoparticles.",isbn:"978-953-51-3940-9",printIsbn:"978-953-51-3939-3",pdfIsbn:"978-953-51-3989-8",doi:"10.5772/65837",price:119,priceEur:129,priceUsd:155,slug:"unraveling-the-safety-profile-of-nanoscale-particles-and-materials-from-biomedical-to-environmental-applications",numberOfPages:172,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"5e5811aa0f15ab9d8b6a235e8408875d",bookSignature:"Andreia C. Gomes and Marisa P. Sarria",publishedDate:"March 21st 2018",coverURL:"https://cdn.intechopen.com/books/images_new/5884.jpg",numberOfDownloads:10013,numberOfWosCitations:30,numberOfCrossrefCitations:34,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:58,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:122,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 18th 2016",dateEndSecondStepPublish:"November 8th 2016",dateEndThirdStepPublish:"July 16th 2017",dateEndFourthStepPublish:"August 16th 2017",dateEndFifthStepPublish:"October 16th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"146466",title:"Prof.",name:"Andreia",middleName:null,surname:"Ferreira de Castro Gomes",slug:"andreia-ferreira-de-castro-gomes",fullName:"Andreia Ferreira de Castro Gomes",profilePictureURL:"https://mts.intechopen.com/storage/users/146466/images/system/146466.jpeg",biography:"Andreia C. Gomes, BSc, PhD, is Vice-Director of CBMA – Centre of Molecular and Environmental Biology and member of the Scientific Council of IB-S (Institute of Science and Innovation for Bio-Sustainability). She is Assistant Professor in the Department of Biology at University of Minho since 2007 and co-founder of spin-off Nanodelivery-I&D em Bionanotecnologia, Lda. \r\nShe has co-authored 3 patents and almost 80 publications, and supervised several Master, Doctoral and Postdoctoral students.\r\nHer actual research interests are focused on the study of the interface between nanostructured materials and cells and tissues, as to optimize biological and/or therapeutic effect with minimal toxicity risk.",institutionString:"University of Minho",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Minho",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"196010",title:"Dr.",name:"Marisa",middleName:null,surname:"P. Sárria",slug:"marisa-p.-sarria",fullName:"Marisa P. Sárria",profilePictureURL:"https://mts.intechopen.com/storage/users/196010/images/system/196010.jpeg",biography:"Marisa P Sarria, BSc, PhD, joined the INL - International Iberian Nanotechnology Laboratory - Braga, Portugal - in 2015 as a Marie Curie Research Fellow. Her COFUND project was devoted to develop innovative nanoagents for delivery of marine toxins towards therapeutical applications. Dr. Sarria actual research interests focus on investigation of the toxicological profile of nanoparticles and nanomaterials. For the excellence of her academic path, she was granted with three merit awards. In 2011, she was awarded with distinction a Doctoral degree in Biology, at the University of Porto - Porto, Portugal. As post-doctoral researcher at University of Minho from 2012 to 2014, she collaborated in large-scale European projects committed to develop nanobiodevices for integrated theranostics targeting human diseases.",institutionString:"INL - International Iberian Nanotechnology Laboratory",position:"Research Fellow",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"17",title:"Nanotechnology and Nanomaterials",slug:"nanotechnology-and-nanomaterials"}],chapters:[{id:"56166",title:"Spectroscopic Insights into the Nano-Bio Interface",doi:"10.5772/intechopen.69384",slug:"spectroscopic-insights-into-the-nano-bio-interface",totalDownloads:1081,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Engineered nanomaterials (ENMs) strongly interact with biomolecules due to their unique physicochemical properties. From the standpoint of nanotoxicity, it is imperative to achieve a comprehensive understanding of various nano-bio interactions to ultimately design benign ENMs that do not elicit adverse physiological responses. Spectroscopic tools are ideal for elucidating the underlying biophysical mechanisms of nano-bio interactions. In this chapter, we review spectroscopy techniques, such as Raman, infrared, circular dichroism (CD), and hyperspectral imaging, to illuminate the nano-bio interface. Particularly, we discuss the role of spectroscopic tools in gaining a fundamental understanding of the formation and influence of protein corona on ENM physiological responses.",signatures:"Achyut J. Raghavendra, Wren Gregory, Indushekhar Persaud, Jared\nM. Brown and Ramakrishna Podila",downloadPdfUrl:"/chapter/pdf-download/56166",previewPdfUrl:"/chapter/pdf-preview/56166",authors:[{id:"182386",title:"Prof.",name:"Ramakrishna",surname:"Podila",slug:"ramakrishna-podila",fullName:"Ramakrishna Podila"}],corrections:null},{id:"58859",title:"Toxicological Risk Assessment of Emerging Nanomaterials: Cytotoxicity, Cellular Uptake, Effects on Biogenesis and Cell Organelle Activity, Acute Toxicity and Biodistribution of Oxide Nanoparticles",doi:"10.5772/intechopen.71833",slug:"toxicological-risk-assessment-of-emerging-nanomaterials-cytotoxicity-cellular-uptake-effects-on-biog",totalDownloads:1196,totalCrossrefCites:8,totalDimensionsCites:11,hasAltmetrics:1,abstract:"The lack of toxicological data on nanomaterials makes it difficult to assess the risk related to their exposure, and as a result further investigation is required. This chapter presents the synthesis of controlled oxide nanoparticles followed by the evaluation of their safety profile or toxicity (iron, titanium and zinc oxides). The controlled surface chemistry, dispersion in several media, morphology and surface charge of these nanoparticles are presented (transmission electron microscopy, dynamic light scattering, zeta potential, X-ray photoelectron spectroscopy). Classical cytotoxic and cellular uptake studies on different cancer cell lines from liver, prostate, heart, brain and spinal cord are discussed. The incidence of nanoparticles on biogenesis and activity of cell organelles is also highlighted, as well as their biodistribution in animal models. The acute toxicity on zebrafish embryo model is also presented. Finally, the stress is put on the influence and the necessity of controlling the protein corona, a layer of plasma proteins physically adsorbed at the surface of such nanoparticles as a result of their presence in the bloodstream (or relevant biological fluids).",signatures:"Lionel Maurizi, Anne-Laure Papa, Julien Boudon, Sruthi\nSudhakaran, Benoist Pruvot, David Vandroux, Johanna Chluba,\nGérard Lizard and Nadine Millot",downloadPdfUrl:"/chapter/pdf-download/58859",previewPdfUrl:"/chapter/pdf-preview/58859",authors:[{id:"217080",title:"Prof.",name:"Nadine",surname:"Millot",slug:"nadine-millot",fullName:"Nadine Millot"},{id:"220403",title:"Dr.",name:"Lionel",surname:"Maurizi",slug:"lionel-maurizi",fullName:"Lionel Maurizi"},{id:"220404",title:"Dr.",name:"Anne-Laure",surname:"Papa",slug:"anne-laure-papa",fullName:"Anne-Laure Papa"},{id:"220405",title:"Dr.",name:"Julien",surname:"Boudon",slug:"julien-boudon",fullName:"Julien Boudon"},{id:"220406",title:"MSc.",name:"Sudhakaran",surname:"Sruthi",slug:"sudhakaran-sruthi",fullName:"Sudhakaran Sruthi"},{id:"220407",title:"Dr.",name:"David",surname:"Vandroux",slug:"david-vandroux",fullName:"David Vandroux"},{id:"220408",title:"Prof.",name:"Gérard",surname:"Lizard",slug:"gerard-lizard",fullName:"Gérard Lizard"},{id:"221278",title:"Prof.",name:"Johanna",surname:"Chluba",slug:"johanna-chluba",fullName:"Johanna Chluba"},{id:"221279",title:"Dr.",name:"Benoist",surname:"Pruvot",slug:"benoist-pruvot",fullName:"Benoist Pruvot"}],corrections:null},{id:"55667",title:"Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects",doi:"10.5772/intechopen.69386",slug:"interaction-of-nanoparticles-with-blood-components-and-associated-pathophysiological-effects",totalDownloads:1947,totalCrossrefCites:16,totalDimensionsCites:26,hasAltmetrics:1,abstract:"Nanotechnology currently plays a pivotal role in several fields and has enabled substantial advances in a relatively short time. In biomedicine, nanomaterials can be potentially employed as a tool for early diagnosis and an innovative mode of drug delivery. Novel nanomaterials are currently widely manipulated without a full assessment of their potential health risks. It is commonly thought that nanomaterials’ first contact with the organism is through the different components of the immune system. However, if the entry route is intravenous, the first contact will be with the blood’s components (erythrocytes, platelets, white cells, plasma and complement proteins). The presence of nanomaterials within a dynamic environment such as the bloodstream can produce potential harmful effects following interaction with several blood components. The design of innovative strategies leading to the development of more hemocompatible nanomaterials is also necessary.",signatures:"Gerardo González De La Cruz, Patricia Rodríguez-Fragoso, Jorge\nReyes-Esparza, Anahí Rodríguez-López, Rocío Gómez-Cansino and\nLourdes Rodriguez-Fragoso",downloadPdfUrl:"/chapter/pdf-download/55667",previewPdfUrl:"/chapter/pdf-preview/55667",authors:[{id:"141589",title:"Prof.",name:"Lourdes",surname:"Rodriguez-Fragoso",slug:"lourdes-rodriguez-fragoso",fullName:"Lourdes Rodriguez-Fragoso"},{id:"193799",title:"Dr.",name:"Jorge",surname:"Reyes-Esparza",slug:"jorge-reyes-esparza",fullName:"Jorge Reyes-Esparza"},{id:"199729",title:"Dr.",name:"Patricia",surname:"Rodríguez-Fragoso",slug:"patricia-rodriguez-fragoso",fullName:"Patricia Rodríguez-Fragoso"},{id:"199730",title:"Dr.",name:"Gerardo",surname:"González De La Cruz",slug:"gerardo-gonzalez-de-la-cruz",fullName:"Gerardo González De La Cruz"},{id:"204909",title:"MSc.",name:"Anahi",surname:"Rodríguez-López",slug:"anahi-rodriguez-lopez",fullName:"Anahi Rodríguez-López"},{id:"204987",title:"Dr.",name:"Rocío",surname:"Gómez-Cansino",slug:"rocio-gomez-cansino",fullName:"Rocío Gómez-Cansino"}],corrections:null},{id:"57434",title:"Cytotoxic and Antiproliferative Effects of Nanomaterials on Cancer Cell Lines: A Review",doi:"10.5772/intechopen.71685",slug:"cytotoxic-and-antiproliferative-effects-of-nanomaterials-on-cancer-cell-lines-a-review",totalDownloads:1637,totalCrossrefCites:2,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Cell models for the study of antiproliferative and/or cytotoxic properties of engineered nanoparticles are valuable tools in cancer research. Several techniques and methods are readily available for the study of nanoparticles’ properties regarding selective toxicity and/or antiproliferative effects. Setting up of those techniques, however, needs to be carefully monitored. Harmonization of the wide range of methods available is necessary for assay comparison and replicability. Although individual or core laboratory capabilities play a role in selection and availability of techniques, data arising from cancer cell models are useful in guiding further research. The variety of cell lines available and the diversity of metabolic routes involved in cell responses make in vitro cell models suitable for the study of the biological effect of nanoparticles at the cell level and a valid approach for further in vivo and clinical studies. The present systematic review looks at the in vitro biological effects of different types of nanoparticles in cancer cell models.",signatures:"Marcelo Grijalva, María José Vallejo-López, Lizeth Salazar, Javier\nCamacho and Brajesh Kumar",downloadPdfUrl:"/chapter/pdf-download/57434",previewPdfUrl:"/chapter/pdf-preview/57434",authors:[{id:"76070",title:"Dr.",name:"Javier",surname:"Camacho",slug:"javier-camacho",fullName:"Javier Camacho"},{id:"176093",title:"Dr.",name:"Brajesh",surname:"Kumar",slug:"brajesh-kumar",fullName:"Brajesh Kumar"},{id:"214600",title:"Dr.",name:"Marcelo",surname:"Grijalva",slug:"marcelo-grijalva",fullName:"Marcelo Grijalva"},{id:"214602",title:"MSc.",name:"María José",surname:"Vallejo",slug:"maria-jose-vallejo",fullName:"María José Vallejo"},{id:"214603",title:"BSc.",name:"Lizeth",surname:"Salazar",slug:"lizeth-salazar",fullName:"Lizeth Salazar"}],corrections:null},{id:"55788",title:"Nanotoxicity in Cancer Research: Technical Protocols and Considerations for the Use of 3D Tumour Spheroids",doi:"10.5772/intechopen.69447",slug:"nanotoxicity-in-cancer-research-technical-protocols-and-considerations-for-the-use-of-3d-tumour-sphe",totalDownloads:1619,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The poor clinical translation of oncological nanomedicine products is one of the greatest challenges faced by research today. The use of reductionist in vitro models of human cancer and non-predictive animal models is generally considered as one of the main causes of such very low translation rate. The integration of three-dimensional (3D) tumour spheroids in the early stages of the preclinical screening pipeline could significantly facilitate the translation of nanomedicine candidates into clinical practice, by allowing for a more reliable prediction of their efficacy and safety in humans. To lead a successful integration of 3D spheroids, protocols that satisfy issues of ease-of-use, reproducibility and compatibility with conventional and high-throughput assays, without losing the advantages offered by two-dimensional (2D) cell systems, are still needed. To address such need, protocols for the formation and characterisation of scaffold-free 3D tumour spheroids of human adenocarcinoma cells were developed and optimised in this study for their application in nanomedicine safety testing. The protocols reported in this chapter provide the ground on how 3D tumour spheroids could be implemented to design nanomedicine products and speed up experimental cancer research, eliminating those candidates that are likely to be ineffective or unsafe in human at early development stages.",signatures:"Dania Movia and Adriele Prina-Mello",downloadPdfUrl:"/chapter/pdf-download/55788",previewPdfUrl:"/chapter/pdf-preview/55788",authors:[{id:"199318",title:"Prof.",name:"Adriele",surname:"Prina-Mello",slug:"adriele-prina-mello",fullName:"Adriele Prina-Mello"},{id:"200781",title:"Dr.",name:"Dania",surname:"Movia",slug:"dania-movia",fullName:"Dania Movia"}],corrections:null},{id:"58702",title:"Applications of Fluorescent Quantum Dots for Reproductive Medicine and Disease Detection",doi:"10.5772/intechopen.72978",slug:"applications-of-fluorescent-quantum-dots-for-reproductive-medicine-and-disease-detection",totalDownloads:1334,totalCrossrefCites:5,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Understanding the mechanisms associated with fertility and disease management in animals remains challenging. Continuing advances in nanotechnology provide new tools and alternative approaches for the investigation of these mechanisms. Fluorescent quantum dot nanoparticles, for example, have unique physicochemical properties, which allow for in vivo and in vitro imaging in various areas of life sciences. Traditional quantum dots contain heavy metal semiconductor cores, which have raised concern over their potential for toxicity. The majority of available quantum dots today prevent heavy metal release with additional chemical and polymer layers for safe water solubility. In this chapter, the most widely used quantum dots made of cadmium selenide, which possess great potential for real-time imaging in disease detection and reproductive medicine, are discussed.",signatures:"Sapna Jain, Seong B. Park, Shreekmar R. Pillai, Peter L. Ryan, Scott T.\nWillard and Jean M. Feugang",downloadPdfUrl:"/chapter/pdf-download/58702",previewPdfUrl:"/chapter/pdf-preview/58702",authors:[{id:"213129",title:"Dr.",name:"Nguekam",surname:"Feugang",slug:"nguekam-feugang",fullName:"Nguekam Feugang"}],corrections:null},{id:"59716",title:"Bioaccumulation and Toxic Profiling of Nanostructured Particles and Materials",doi:"10.5772/intechopen.74802",slug:"bioaccumulation-and-toxic-profiling-of-nanostructured-particles-and-materials",totalDownloads:1199,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Use of nanotechnological based formulations and nanomaterials are increasing day-by-day in wide range covering a broad typology of applications, from design and development of targeted drug delivery systems, manufacturing of pesticides, domestic appliances, textiles, to bioremediation engineering. There are therefore concerns about the environmental risks or bioaccumulation-related issues that may arise particularly resulting from the application of drug-loaded nanocarriers or effect of pesticides that reach the natural ecosystems. This is a major threat in the present era and needs to be balanced against their undoubted benefits to human society. The assessment of the physical and chemical properties of nanoparticles and nanomaterials influencing their toxic manifestation due to accumulation in human or in animal organs is still poorly investigated. This chapter reviews the possibilities of bioaccumulation of different nanoscale particles and materials, their potential acute and subacute toxicological profile and their identification and characterization in different organs and tissues of vertebrates.",signatures:"Subas Chandra Dinda",downloadPdfUrl:"/chapter/pdf-download/59716",previewPdfUrl:"/chapter/pdf-preview/59716",authors:[{id:"212255",title:"Prof.",name:"Subas",surname:"Dinda",slug:"subas-dinda",fullName:"Subas Dinda"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7325",title:"Nanostructures in Energy Generation, Transmission and Storage",subtitle:null,isOpenForSubmission:!1,hash:"8e49924dd2c3e28c82fdc115ce04f925",slug:"nanostructures-in-energy-generation-transmission-and-storage",bookSignature:"Yanina Fedorenko",coverURL:"https://cdn.intechopen.com/books/images_new/7325.jpg",editedByType:"Edited by",editors:[{id:"199149",title:"Dr.",name:"Yanina",surname:"Fedorenko",slug:"yanina-fedorenko",fullName:"Yanina Fedorenko"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9322",title:"Hybrid Nanomaterials",subtitle:"Flexible Electronics Materials",isOpenForSubmission:!1,hash:"beff6cce44f54582ee8a828759d24f19",slug:"hybrid-nanomaterials-flexible-electronics-materials",bookSignature:"Rafael Vargas-Bernal, Peng He and Shuye Zhang",coverURL:"https://cdn.intechopen.com/books/images_new/9322.jpg",editedByType:"Edited by",editors:[{id:"182114",title:"D.Sc.",name:"Rafael",surname:"Vargas-Bernal",slug:"rafael-vargas-bernal",fullName:"Rafael Vargas-Bernal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9230",title:"Smart Nanosystems for Biomedicine, Optoelectronics and Catalysis",subtitle:null,isOpenForSubmission:!1,hash:"1d1af591d87490c9ad728a1352e62d96",slug:"smart-nanosystems-for-biomedicine-optoelectronics-and-catalysis",bookSignature:"Tatyana Shabatina and Vladimir Bochenkov",coverURL:"https://cdn.intechopen.com/books/images_new/9230.jpg",editedByType:"Edited by",editors:[{id:"237988",title:"Prof.",name:"Tatyana",surname:"Shabatina",slug:"tatyana-shabatina",fullName:"Tatyana Shabatina"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10463",title:"Nanomechanics",subtitle:"Theory and Application",isOpenForSubmission:!1,hash:"c0c14ad42c145ac8720b4ab4d666f395",slug:"nanomechanics-theory-and-application",bookSignature:"Alexander V. 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To build and design a real smart environment, these advancements are supported by huge developments in many research and industrial areas such as ubiquitous computing, wireless mobile communications, portable appliances and devices, wireless sensor networking, machine learning-based decision-making, agent technologies, IPv6 support, and human computer interfaces. A smart environment has sensor-enabled devices working collaboratively to build a small connected world for making the lives of people more comfortable and adaptable. The term smart refers to the ability to autonomously obtain and apply knowledge, and the term environment refers to the surroundings. Therefore, a smart environment can be adapted by obtaining knowledge and applying it according to its users’ requirements to improve their experience of that environment. In addition, the interconnection among different smart objects can enhance their functional capabilities [1]. In this context, IPv6 plays a vital role because of several features, including scalability in the case of billions of connected devices, better security mechanisms, and the elimination of network address translation (NAT) barriers. The “Internet of Things” (IoT) concept was first coined by Kevin Ashton, where smart objects are connected with the Internet.
\nNowadays, IoT is receiving attention in many fields such as transport, agriculture, industry, and healthcare [2, 3]. Cisco reports that 50 billion devices and objects will be connected to the Internet by 2020. Also, the Internet of Things (IoT) will contribute $117 billion to the IoT-based healthcare industry and $1.9 trillion to the global economy according to Gartner and Forbes. In addition, according to Automotive News, the number of cars connected to the Internet worldwide will increase from 23 million in 2013 to 152 million in 2020. According to another report from Navigant Research, the number of installed smart meters around the world will grow to 1.1 billion by 2022. The prediction of such significant growth shows that IoT will become the umbrella of modern societies to realize the vision of smart environments. A lot of research efforts have been developed to integrate IoT with smart environments. To enable the user for monitoring the environment remotely or from remote sites, the integration of IoT with a smart environment is needed to extend the capabilities of smart objects. Based on the application requirements, IoT can be integrated with different smart environments. So, IoT-based smart environments can generally be classified into the following areas: (a) smart homes, (b) smart buildings, (c) smart cities, (d) smart grid, (e) smart health, (f) smart transportation, (g) smart industry, and (h) smart agriculture. Figure 1 illustrates the IoT-based smart environments.
\nIoT-based smart environments.
There are many open challenges that have been described by various researchers including those related to power supply, enabling a complex sensing environment, evolving architecture, multiple connectivity options, complexity of IoT, security of information exchange within IoT, and privacy [4, 5, 6]. Due to the lack of a clear and widely accepted business model that can engage investments to encourage the deployment of these technologies, there is difficulty in the adoption of the IoT paradigm [3].
\nTo a certain extent, the above-mentioned challenges can be met, with the aid of a variety of wireless and wired connectivity options, such as radio frequency identification (RFID), near-field communication (NFC), Bluetooth, and Wi-Fi. These connectivity options are categorized into three broad types considering their geographical area coverage, that is, personal area network (PAN), local area network (LAN), and wide area network (WAN) [7]. Figure 2 shows this categorization. The existing Wi-Fi networks should be modified to attain a wider coverage and to support mesh networks [8]. In addition, the confirmation on communication pathway of IoT is very important to understand the information exchange within IoT. It uses various standards, techniques, and protocols to disseminate information.
\nIoT communication technologies [
It is essential to support device-to-device (D2D), device-to-server (D2S), and server-to-server communications (S2S) to facilitate information sharing within the IoT [7, 9]. There are multiple standards and protocols involved with IoT communication. Some of these standards and protocols take a higher priority, such as Internet Protocol version 4 (IPv4), Internet Protocol version 6 (IPv6), IPv6 over Low-Power Wireless Personal Area Network (6LoWPAN), User Datagram Protocol (UDP) Constrained Application Protocol (CoAP), and Transmission Control Protocol (TCP). However, UDP is advantageous and cost-effective, due to its smaller size and performance according to constrained device developers [10]. To find a model for arranging these protocols into constrained and unconstrained stacks according to the TCP/IP network layer architecture, some efforts were made. The unconstrained stack contains Hypertext Transfer Protocol (HTTP), common standards Extensible Markup Language (XML), and IPv4, whereas the constrained stack contains Efficient XML Interchange (EXI), CoAP, and 6LoWPAN which are protocols with similar functionality but the complexity is reduced significantly [3]. In real life, the IoT has been rapidly developed and deployed with the enormous contribution from companies and research centers [11]. However, IEEE 802.11, IEEE 802.3, and IEEE 802.15.4 are the most common standards related to IoT [10], and the Internet Engineering Task Force (IETF) protocol suite has a vital contribution toward IoT for determining the challenges for IoT [12]. So, recently IoTs are widely accepted for using in practical application scenarios. Matrices are available to measure the cost, processing speed, and communication speed. However, there are few studies on application layer protocols and performance of 6LoWPAN [13, 14], IPv6 routing protocol for low power and lossy networks (RPL) [15, 16, 17], and IEEE 802.15.4 [18]; a complete evaluation of IoT has not taken place until now. Hence, this gap needs to be filled up in near future, considering a holistic view of IoT.
\nIn this section, common major challenges of IoT and its future directions will be introduced. These challenges are
In critical applications, reliability is very important [23]. Reliability is not just sending reliable information, but being able to adapt to changing environmental conditions, be resistant to long-term usability and security problems [24]. In all aspects of software and hardware of IoT, reliability requires to be guaranteed. Attempts were made to explain clearly with the architecture considerations, the reliability consideration for transport, link, and application layers together [24]. Moreover, to describe and analyze reliability and cost-related properties of the service composition in IoT, a probabilistic approach was proposed [25].
\nSecurity and privacy are an essential requirement of most of the applications. In IoT, memory cards of a device have a limited storage capacity. So, only small amounts of data can be stored in them, and some of the data will be stored in other sites remotely. For these remote data, users do not want to disclose their information to others, so these data need high security and privacy. In terms of security, privacy, and governance rules, new technology is required to give users the ability to verify whether the company satisfies their service level agreement or not, dynamically. Therefore, they should adapt pertinent mechanisms for IoT, to meet the expected security level of a user. Privacy, communication, trusted sensing, computation, and digital forging are rarely addressed tasks in terms of security scope [26]. IoT does not adhere to common security standards and architecture; however, security has become a very important issue [27]. Traditional security architectures cannot fully satisfy the security requests of IoT, because of the existence of a huge number of heterogeneous devices that are connected together. As result, there is a large number of malware entry points, which increases vulnerability. By applying a biological immunology approach, a scheme has been proposed based on a dynamic defense security mechanism to alleviate these security issues in an IoT architecture [28]. In [26], attempts were done to secure IoT communications by ensuring the security of IoT devices. As the first step, computer-aided design (CAD) techniques have been proposed to design IoT devices, which are highly optimized in both energy and security. Importantly, compared to the expensive hardware-securing concepts proposed, CAD techniques can be used to implement strong and ample security with low cost. However, it is practically not in use until date.
\nIn literature, there are several approaches for tackling the security issues in the current IoT paradigm. However, the authentication of devices and securing links in a dynamic mobility environment are still unresolved challenges. Thus, the authentication of IoT devices in real-world scenario still has unresolved issues. Researchers have warned of a realistic threat to the IoT community in the future in industries called “smart home hacking” to meet these challenges.
\nThe increase in the number of smart devices and the advances of embedded technologies have increased the devices-to-person ratio up to 1.84 in 2010 [29]. In addition, the requirements from applications by a client increase over the time. So, the scalability of IoT, which is the ability to add more devices and services to IoT without degrading the Quality of service (QoS), must be considered. Due to the heterogeneity of devices and underlying technologies, scalability becomes a critical issue in IoT. To enable unified addition of new devices via a layered architecture, a distributed, interoperable architecture was proposed for IoT to address the scalability issues without degrading the QoS for the realization of IoT notion [30]. In [30], the authors propose three layers of IoT infrastructure: (1) virtual object layer (VOL), (2) composite virtual object layer (CVOL), and (3) service layer (SL). The base structure “IoT daemon” of the distributed architecture consists of the functionalities of the three layers which are object virtualization, service composition and execution, and service creation and management. Based on the processing power and memory, every object hosts its own IoT daemon. Various applications are unified by using the three layers of IoT daemon. VOL digitally represents the properties and functionalities of each object. However, to perform a task, multiple objects work in collaboration. Thus, during runtime, composite virtual object (CVO) is created as a mash-up of VOs corresponding to the task. To create a mash-up, potential VOs should be identified, which is done at the CVOL. With the aid of uniform representation of objects (virtual object (VO)), addition of new objects to the IoT network does not degrade QoS because all the devices are connected with distributed architecture. Also, there are scalability issues due to the increase of network elements (NEs) in the Internet. Compensating the scalability issues with a service-oriented path computation element (S-PCE) instead of conventional host-oriented PCE was proposed by Barbosa C. Souza et al. in [31]. The performance evaluation confirmed that the proposed model supports more network elements than host-oriented PCE by comparing results obtained and the logs of DNS servers [31].
\nInteroperability is another major concern with regard to IoT, since various types of devices are connected to each other via IoT. Hence, IoT should facilitate services to all these devices regardless of the type, as interoperability is a necessity. By adhering to standardized protocols, this can be achieved to a certain level at the network and application levels. Due to ambiguous interpretations of the same protocol, achieving interoperability is challenging. So, by avoiding such ambiguities, interoperability of IoT would become more realistic. In [32], a solution to address IoT resources using Web protocols via IoT hubs has been proposed. Thus, the interoperability challenges are reduced to data formats and presenting hub catalogues.
\nIn IoT, most of the devices are mobile devices, which make the IoT scenario more complex. So, IoT applications need to deliver services by considering the mobility factor as well. There are available standard management protocols, that is Mobile IPv6 (network layer) and TCP migrate (transport layer), to facilitate mobility issues in IoT. However, these standards are too complex to be used in IoT nodes. For constrained devices in IoT, a CoAP-based mobility protocol (CoMP) was proposed [33]. Moreover, to ensure mobility, a group mobility management (GMM) mechanism is shown to be promising [34]. In this context, the leader machine does mobility management for the group of machines that are grouped according to mobility patterns.
\nPrecision is another one of the most important challenges that need to be addressed in many smart IoT environments such as transportation, healthcare, and unmanned aerial vehicular networks, where devices and systems are connected globally. Compliance with stringent requirements becomes central to the health and safety of the machine operators, machines, and related businesses when dealing with precision machines that can fail if the timing is 1 ms. Available bandwidth and network latency are the key factors that can affect the precision of distributed IoT delay-sensitive mission-critical environments. Therefore, when deploying IoT in a smart environment, these parameters need to be considered. For example, longer network latencies can cause delays in applying car brakes and be very dangerous in the case of vehicle-to-vehicle communication in smart transportation environments. Successful IoT deployment in smart environments can be achieved by designing and developing high-precision systems.
\nBig data are another challenge in IoT because IoT is one of the largest sources of collecting large amounts of data. As mentioned earlier, by 2020 more than 50 billion devices will be connected with each other, which can lead to big data production. The performance of most IoT applications is based on the data management services. Therefore, due to big data generated by devices forming a smart IoT environment, managing the big IoT data in terms of processing, access, and storage requires highly scalable computing platforms that do not affect the performance of the application.
\nCompatibility is another challenge in an IoT-based smart environment, where various products are connected with each other. Due to the unavailability of a universal language, most of the products are unable to connect with each other and lead to compatibility issues. To connect devices with each other, collaboration among enterprises, such as LG, Philips, and Samsung, is required. People will be frustrated if these companies are not collaborated and they are only capable of using one brand, in this case. Therefore, the collaboration among these companies is demanded to obtain the infrastructure information of each product and design a universal coding language accordingly by developers. To ensure the success of IoT, a solution to compatibility issues is demanded.
\nMassive investment in IoT scenario is required for the investment decision to deploy an industrial IoT environment. In IoT, there is a difficulty for industries to adopt this technology where things are not open and interoperable in terms of hardware and software. Therefore, open and integrated hardware and software-based IoT solutions should be built for deployment in industries. In addition, instead of replacing these deployments with new systems, the solutions should be flexible enough for enabling industries to evolve and adapt to their changes. Expertise and investment are required for generating innovation within existing hardware and software architectures.
\nIn this section, the state-of-the-art IoT-based smart systems are presented and categorized and classified according to application domain. The main categories are as follows: (a) smart homes, (b) smart building, (c) smart cities, (d) smart grid, (e) smart health, (f) smart transport, (g) smart industry, and (h) smart agriculture.
\nIn [35], for detecting a fault in the software defined network (SDN)-based smart home environment, a cloud-based home solution was proposed. To find the faulty location in an IoT-based smart home environment, four social relationships are defined, namely, IoTService, IoTphysical space, IoTNetwork, and IoTIoT. An SDN controller makes a status graph that contains information on each home IoT to resolve the dependencies by collecting information from the packets passing through SDN switches, and the stateless protocol is used by Web-based services, which are not made for long-term sessions.
\nIn terms of cost, accuracy, intrusiveness, and privacy, existing occupancy monitoring approaches were analyzed by Akkaya et al. in [36]. For improving the occupancy detection accuracy in a smart building, they used multi-modal data fusion. In the information fusion techniques, noisy measurements generated from IoT devices are filtered and occupancy status is predicted. To reduce the energy consumption of the smart building, they also investigated how occupancy monitoring techniques could be used with data fusion techniques. EUFP7 IoT is a project to devise authentication and authorization mechanisms for service access protection. To extend the security functionalities stated by the architectural reference model for EUFP7 IoT, the framework was proposed in [37]. In [37], the authors proposed this framework to utilize the available localization data and to implement the access control for services provided in smart building. The proposed framework is based on a service management platform which is a city explorer that implements the key security aspects.
\nFor urban IoT, the authors in [3] presented a survey on the architectures, protocols, and enabling technologies. They describe link layer technologies, Web service-based IoT architecture, and devices suitable for the urban IoT architecture. To enable various IoT applications, a generic top-down IoT architecture for smart cities was proposed in [38]. The integrated information center run by the IoT service provider is the core element of this architecture. This information center is connected to a set of services, such as water, electrical energy, central gas supply, provided in smart cities. Several technologies that are essential for the realization of smart cities, such as IoT co-building, openness, and convergence, are facilitated by this architecture.
\nIn [39], Al-Hader et al. proposed a five-level pyramid architecture for smart cities as shown in Figure 3. The bottom layer is the smart infrastructure layer including water, electronics, fire protection, natural gas, electronic communications, and network. The next layer is the smart database resources layer including database server, data resources, and databases. The next layer is the smart building management system layer including building automation, control network, and HVAC. The next layer is the smart interface layer including dashboard, common operational platform, and integrated Web services. The top layer is the smart city. Some of the major functionalities that can be included in smart cities are street lighting, maintenance, waste management, surveillance, building, and emergency health monitoring.
\nA pyramid architecture for smart cities [
In [40], an IoT-based real-time monitoring system was proposed for power transmission lines to avoid disasters. In the proposed system, conductor galloping, wind deviation, conductor temperature, icing, and tower leaning are visually displayed at the monitoring center. These parameters represent the power transmission lines and operational parameters of the tower. So, the system can implement real-time monitoring and early warnings of disaster for minimizing the damage of smart grid caused by natural disasters. In [41], IoT-based smart grid applications were classified into three types: (a) key equipment state monitoring, (b) information collection, and (c) smart grid control. It also describes the types and characteristics of IoT-based smart grids. As a result, a reference architecture for smart grid IoT based on the characteristics was proposed. There are three layers in this reference architecture: perception layer, transport layer, and application layer. For security protection of IoT-based smart grids, a secure access control system is proposed for ensuring that IoT-based smart grid devices can securely access the Internet.
\nIn [42], to monitor, collect, and transmit remote healthcare data, a system architecture based on IoT was proposed. To transfer data to a gateway, IEEE 802.15.4 standard was used and static and adaptive rule engines were developed as well. Through transmitting data based on important parameters extracted from the collected data, these two rules are involved in the decision-making process. As a result, these developed rule engines can minimize network traffic and save energy consumption. To solve issues such as reliability, interoperability, performance, energy efficiency, scalability, and security, the authors in [43] presented a smart e-Health gateway based on IoT. Based on taking responsibility of handling the sensor networks implemented in the remote healthcare center, this smart gateway can address these issues. The authors presented a case study called UTGATE for this smart e-Health gateway. Based on the achieved results from this case study, the smart e-Health gateway can provide services such as fast data processing, storage, and embedded data mining.
\nThe IoT can be used in all aspects of transportation such as geo services, collection of data related to passenger counting, communication, and smart ticketing. In [44], Eurotech provides IT solutions that can help in connecting every public transport element and use the technical tools to connect IT infrastructure with sensors and other devices. To enhance the traffic conditions in cities, the Kapsch Group in [45] investigated how Internet technologies can be leveraged.
\nIn [46], the authors presented smart factory based on IoT architecture and defined issues such as optimized decision-making, flexibility, remote monitoring, and mass customization, with respect to energy management. By using the proposed mechanism, energy consumption is improved in a smart factory by incorporating energy data into production management.
\nWater utilization and irrigation can be improved by leveraging weather forecast and farm data, key trends and anomalies, and evapotranspiration index. Building IoT-based smart farming will enable farmers and growers to reduce waste and enhance productivity ranging from the number of journeys the farm vehicles have made to the quantity of fertilizer utilized. In IoT-based smart farming, with the help of sensors such as light, humidity, temperature, soil moisture sensors, a system is built for monitoring the crop field and automating the irrigation system. This system is highly efficient when compared with the conventional approach, and it gives farmers the ability to monitor the field conditions from anywhere.
\nBecause of the increasing awareness of environmental issues all over the world, green IoT technology initiatives should be taken into consideration. The concept of greening IoT refers to the technologies that make the IoT environment more healthy in a friendly way by making use of facilities and storages that enable subscribers to gather, store, access, and manage various information. The enabling technologies for green IoT are called information and communication technologies (ICTs) [47]. ICTs can cause climate change in the world [48, 49, 50, 51, 52] because with the growing application of ICT much more energy has been consumed. The consideration for sustainability of ICTs has concentrated on data centers optimization through techniques of sharing infrastructure, which leads to increasing the energy efficiency, reducing CO2 emissions and e-waste of material disposals [53]. Greening ICT is enabling technologies for green IoT, which includes green wireless sensor networks (GWSNs), green machine-to-machine communication (GM2M), green RFID, green data center (GDC) [5], green cloud computing (GCC), green Internet, and green communication network as shown in Figure 4. Therefore, green ICT technologies play an essential role in green IoT and provide many benefits to the society such as decreasing the energy used for designing, manufacturing, and distributing ICT devices and equipment.
\nGreen ICT technologies.
Greening IoT is the practice of designing, manufacturing, disposing of computers, servers, and associated subsystems (i.e., monitors, printers, communications equipment, and storage devices) efficiently and more frequently but with reduced effect on the society and the environment [54]. The aim of using green IoT is to look for new resources and minimize IoT devices’ negative impact on the health of humans and its disturbance to the environment. The main objective of greening IoT is to reduce pollution and Co2 emission, exploit environmental conservation, and minimize the costs of things operating and power consumption [55, 56, 57]. Details about industrial emissions are analyzed and provided in [58]. These emissions influence environmental change in different regions and over time. Reducing the energy consumption of IoT devices is needed to make the environment healthier [59]. Due to the continuous development of green ICT technologies, green IoT provides a high possibility to support environmental sustainability and economic growth [57]. These valuable and emerging technologies make the world greener and smarter. Therefore, this section reviews the core of green IoT technologies that demonstrate efforts for constructing a green and smart world.
\nGreen IoT consists of designing and leveraging aspects. Green IoT focuses on reducing IoT energy usage and CO2 emissions, a necessity for building a smart world with the sustainability of intelligent everything. As shown in Figure 5, design elements of green IoT refer to developing computing devices, energy efficiency, communication protocols, and networking architectures [57].
\nGreen IoT environments.
The IoT element can be used to eliminate CO2 emissions, reduce the pollutions and enhance the energy efficiency. Uddin et al. [60] introduced techniques for enhancing the energy efficiency and reducing CO2 emission for enabling green information technology. Since M2M is equipped with sensors and communication add-ons, these devices can communicate with each other and sense the world. However, sensors will consume high power for executing the tasks. In networking, green IoT aims to identify the location of the relay and number of nodes which satisfy budget constraints and energy saving. To achieve a smart and sustainable world, green IoT plays a significant role in deploying IoT to reduce energy consumption [47], CO2 emission [61] and pollution [61, 62, 63]; exploit environmental conservation [64]; and minimize power consumption [65]. Also, green IoT in [66] is defined as “the study and practice of designing, using, manufacturing, and disposing of servers, computers, and associated subsystems such as monitors, storage devices, printers, and communication network systems efficiently and effectively with minimal or no impact on the environment.” There are three concepts for achieving green IoT, namely, design technologies, leverage technologies, and enabling technologies. Design technologies refer to the energy efficiency of devices, communication protocols, network architectures, and interconnections. Leverage technologies refer to cutting carbon emissions and enhancing energy efficiency. Due to green ICT technologies, green IoT has become more efficient through reducing energy, hazardous emissions, resources consumption, and pollution. Consequently, green IoT leads to preserving natural resources, minimizing technology’s impact on the environment and human health, and reducing the cost significantly. Therefore, green IoT is indeed focusing on green manufacturing, green utilization, green design, and green disposal [67]. These issues are described as follows.
The integration of IoT with smart environments has brought about unprecedented opportunities. This section highlights the main opportunities offered by this environment.
\nIn an IoT-based smart environment, organizations can collect data about processes and products for analysis in a real-time manner and provide the analyzed information to make appropriate decisions. Based on the decisions taken, the smart environment can rapidly adapt itself and improve operational efficiency that results in higher customer satisfaction.
\nCost-effective, flexible, and secure cloud-based applications can transform a smart environment into a decision-making platform by collecting data from the environment and transferring them to the cloud through IoT. The key tasks performed in the cloud server are the analysis of these collected data, decision-making, and prediction of environment parameters.
\nIoT gives companies the ability to build new business models and revenue streams that can create many new business opportunities. IoT has the capability to change the way consumers and businesses follow the world. Therefore, consumers and businesses will require new services that can assist them to explore this ultra-connected, changing landscape. In addition, IoT can enable companies to create new revenue streams and services on top of traditional services, for example, vending machine vendors offering inventory management to those who supply the goods in the machine.
\nWith rapid growth in IoT devices, the data produced by the IoT also grow exponentially. The management of such huge amounts of data will be a challenge in terms of performance. Designing intelligent cloud operation management solutions that can ensure the working of a cloud infrastructure at an optimal level will also be necessary.
\nDue to the integration of novel concepts as well as the adaption of existing technologies, IoT is still evolving. Thereby, it supports the development of more competitive, realistic, and advanced IoT-based applications. The development of IoT applications based on the client requirements evolves according to the requirements of the users. Moreover, many organizations and interest groups are prepared to standardize IoT-related technologies to ensure more effective and secure applications.
\nThe bright future of green IoT will change our future environment to become healthy, green, very high QoS, and sustainable socially, environmentally, and economically. Recently, the most exciting areas have focused on greening things such as green design and implementations, green communication and networking, integrated RFIDs and sensor networks, green IoT services and applications, energy-saving strategies, mobility and network management, smart objects, the cooperation of homogeneous and heterogeneous networks, and green localization. The following research fields need to be researched to develop optimal and efficient solutions for greening IoT:
There is a need for unmanned aerial vehicle (UAV) to replace a massive number of IoT devices, especially in agriculture, traffic and monitoring, which will help to reduce power consumption and pollution. UAV is a promising technology that will lead to green IoT with low cost and high efficiency.
Transmission data from the sensor to the mobile cloud must be more useful. Sensor-cloud is integrating the wireless sensor network and mobile cloud. It is a very hot and promising technology for greening IoT. A green social network such as a service (SNaaS) may investigate the energy efficiency of the system, service, WSN, and cloud management.
M2M communication plays a critical role to reduce energy use and hazardous emissions. Smart machines must be smarter to enable automated systems. Machine automation delay must be minimized in case of traffic and taking necessary and immediate action.
Design Green IoT may be introduced from two perspectives which are achieving excellent performance and high QoS. Finding suitable techniques for enhancing QoS parameters (i.e., bandwidth, delay, and throughput) will contribute effectively and efficiently to greening IoT.
While going toward greening IoT, it will be required to use less energy, looking for new resources, minimizing IoT’s negative impact on the health of humans and disturbance to the environment. Then, green IoT can contribute significantly to sustainable, smart, and green environment.
To achieve energy-balancing for supporting green communication between IoT devices, the radio frequency energy harvest should be taken into consideration.
More research is needed to develop the design of IoT devices which helps to reduce CO2 emission and energy usage. The critical task for smart and green environmental life is saving energy and decreasing the CO2 emission.
In this chapter, the overview and benefits of IoT on telecommunication networks and their challenges were introduced to know how to improve our life and society by building smart IoT systems. In addition, the concept of green IoT and its related services and applications were described in detail. Finally, many research fields, which are needed to develop optimal and efficient solutions for greening IoT, were introduced.
\nThis research was supported by the Department of Mathematics, Faculty of Science, Al-Azhar University, Cairo, Egypt. In addition, it was partially supported by King Abdul-Aziz University, Jeddah, Saudi Arabia. I thank both of them for providing guidance to finish this research. I also thank IntechOpen Limited for giving the opportunity for publishing this research work as a book chapter in Telecommunications Networks.
\nChronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder associated with the activity of
The free radical scavengers like alpha-tocopherol may be effective against cancer-associated oxidative stress. The mean serum vitamin E level significantly decreased in CML patients that seems to be quite in agreement with free radical involvement in CML progression [9]. In contrast to antioxidant function of vitamin E in CML, we suggest new modulation mechanisms of vitamin E that could be operative in prevention of CML progression. In particular, we analyzed the modulation function of vitamin E for molecular unblocking of myeloid differentiation potential in CML cells via vitamin E-dependent induction of pivotal transcription factor CEBP alpha (CCAAT/enhancer-binding protein) as myeloid master regulator of myelopoiesis/granulopoiesis and consequently G-CSFR (granulocyte-colony stimulation factor receptor) [10]. Moreover, we have found that vitamin E could be involved in targeting epithelial-mesenchymal transition (EMT) mechanism in CML cells via SNAIL as EMT inducer [11, 12]. Therefore, we propose that vitamin E could be a therapeutic option when CML progresses in setting of imatinib therapy. Finally, since alkaline phosphatase is considered as a marker of stem cells [13], we studied the aberrant expression of placental-like alkaline phosphatase (PLAP) and discovered the potential of vitamin E in remodeling of CML-associated aberrant expression of this enzyme [14]. Vitamin E-dependent induction of tissue non-specific alkaline phosphatase (TNAP) is paralleled by restored CEBP alpha expression as myeloid master regulator in CML cells [14].
Taken together, these findings suggest that vitamin E shows ability of remodeling leukemic stem cell (LSC) phenotype in CML cells to hematopoietic stem cell (HSC) phenotype with myeloid differentiation potential development.
C/EBPα is mainly involved in cell fate decisions for myeloid differentiation [15]. The progression of CML to blast crisis is correlated with down-modulation of C/EBP-alpha contributing to the differentiation block, enhanced proliferation, and development of acute myelogenous leukemia [16, 17]. The level of C/EBPα expression is significantly declined in CML patients [18]. Currently, the deregulation of C/EBP alpha is considered as a paradigm of leukemogenesis [19]. Therefore, C/EBPα is a critical regulator of myeloid development guiding granulocyte and monocyte differentiation.
We have studied the modulating potential of vitamin E as the possible inducer of C/EBP-alpha expression in BCR-ABL-positive CML K562 cells. K562 cell line originated from a CML patient in blast crisis progression is recognized as a model for leukemia research. We studied the effects of vitamin E in K562 cells in comparison with valproic acid with known differentiation properties towards myeloid cells [20, 21, 22].
Valproic acid in a concentration of 4 mM for 48 h reduced the growth rate and cell viability and induced apoptosis in a fraction of K562 cells (up to 30%). As to vitamin E, in the series of our preliminary experiments, no evidence of toxicity has been demonstrated when K562 cells were cultured with vitamin E in a concentration of 100 μM for 48 h. These concentrations were further used in the experiments for assaying the expression of C/EBP-alpha and G-CSFR mRNA. Figure 1A demonstrates that valproic acid did not change significantly the level of mRNA C/EBP expression in K562 cells. On the contrary, vitamin E proved to be an effective inducer of mRNA C/EBP with about 10-fold increase in expression as compared with non-treated K562 cells. When mRNA G-CSFR expression in K562 cells was assessed, both valproic acid and vitamin E induced mRNA of this receptor, with effect of vitamin E surpassed that of VA (Figure 1A and Table 1).
mRNA expression in CML cells modified by vitamin E. (A) The relative levels of mRNA C/EBP-alpha and G-CSFR expression in K562 cells exposed to valproic acid (2 mM) or vitamin E (100 μM) for 48 h. (B) The aberrant AP mRNA detected by qRT-PCR in leukemic cells of the patient with CML blast crisis: 1 – control without primers; 2 – primers to PAP; 3 – primers to TNAP; 4 – primers to IAP. (C) Ectopic gene expression of embryonic PLAP mRNA in peripheral blood cells of the patient with CML, acute myeloid leukemia (AML), and polycytemia vera (PV): 1 – GAPDH, reference gene; 2 – aberrant PLAP. (D) The relative levels of mRNA expression of PLAP, TNAP, and CCAAT-enhancer binding protein alpha (C/EBPα) in K562 cells exposed to vitamin E (100 μM) for 48 h by real time RT-PCR 2¯(ΔCt) method. (E) Relative mRNA expression level of transcription factor Snail and transcription factor CEBPα in CML blast crisis K562 cells exposed to vitamin E (100 μM) and metformin (4 mM) for 48 h. The relative levels of mRNA expression were analyzed by qRT-PCR and calculated by 2¯(ΔCt) method.
N (n = 3) | C/EBP alpha | G-CSFR | ||
---|---|---|---|---|
Fold increase | Standard Deviation, σ | Fold increase | Standard Deviation, σ | |
1 | 8.395 ± 1.481 | 1.219 | 3.930 ± 1.843 | 1.988 |
2 | 9.854 ± 0.023 | 4.626 ± 0.853 | ||
3 | 11.381 ± 1.506 | 5.134 ± 1.357 |
Fold increase C/EBP alpha and G-CSFR mRNA expression (analyzed in triplicates) in gene expression in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
Thease findings are quite confirmed by Tavor et al. [23] have first shown that the restoration of C/EBP-alpha expression in BCR-ABL-positive KCL22 blast cell line provided by transfection with C/EBPα plasmid vector caused a block in the G2/M phase of the cell cycle with gradual increase in apoptosis suggesting that C/EBP-alpha may be considered as a putative target in differentiation therapies in acute myeloid leukemia. C/EBPα directly activates G-CSFR transcription in lineage committing activation of common myeloid progenitor [24, 25, 26]. Therefore, C/EBPα loss is causally connected with early block in myeloid maturation suggesting that C/EBPα is a master regulator of hematopoietic differentiation. The transcription factor C/EBPα is known as a critical regulator of myeloid development, directing granulocyte, and monocyte differentiation [27].
Our findings gave evidence of C/EBP alpha-dependent activation to granulocytic differentiation via targeted increase in G-CSFR expression in vitamin E treated K562 cells. It should be further elucidated whether such effects of vitamin E on myeloid transcription factor C/EBP-alpha are direct or mediated indirectly due to the antioxidant properties of vitamin E. Nevertheless, our data suggest vitamin E-associated hematopoietic differentiation-like potential associated with C/EBPα and G-CSFR up-regulation. Our findings might be very important for future studies of imatinib resistance in CML clinical setting taking into account the recent report by S. Kagita et al. demonstrating correlation of C/EBPα expression with response and resistance to imatinib in CML [28].
LSCs in CML do not depend on BCR-ABL signaling for their survival [29, 30], and their persistence remains a major obstacle to curing CML [31, 32]. The search for new biological markers of LSC phenotype is still relevant today. Placental-like alkaline phosphatase (PLAP) is expressed by many tumors. Its aberrant expression has been considered to be potentially useful as tumor marker [33]. However, the biological background of the role of this aberrant alkaline phosphatase (AP) in cancer is still unclear. The AP activity in blood serum known as nonspecific marker of bone metastasis [33] is also of potential significance for the identification of stem cell phenotype [13, 34]. Moreover, AP activity is a widely accepted marker of stem cells associated with embryonic stem cell pluripotency [35]. The expression of various forms of AP in CML cells has not yet been studied. Therefore, we aimed to analyze the expression patterns of various AP forms in cells originated from CML patients in blast crisis and to modify their expression by vitamin E (100 μM) in K562 cells. We used the primers to three known tissue AP, namely placental AP (PAP), non-specific AP (TNAP) (expressed in bone, kidney, liver) and intestinal AP (IAP) [36] to analyze the mRNA expression of these APs in CML cells by qRT-PCR. We have observed the aberrant expression of mRNA IAP in cells of CML patient in blast crisis (Figure 1B) that upon sequencing (data not shown) demonstrated the significant alignment with known cancer-associated PLAP sequence, while no gene homology with tissue PAP was detected. This fact gave reason to consider revealed PLAP as embryonic-like placental AP (ELAP), to be more precise, the aberrant PLAP in blast cells of CML patients (Figure 1C). Indeed, such PLAP is expressed in early embryo pre-implantation period as was detected in studying mouse embryonic cell development, while tissue TNAP begins to express in post-implantation period [35]. We have not detected TNAP in cells of CML patients. Only the embryonic-like PLAP was detected, which expression also increased in acute myeloid leukemia (Figure 1C). Recently, TNAP recognized ultimately as mesenchymal stromal cell antigen-1 (MSCA-1) [13] was described as a biomarker associated with normal hematopoiesis as well as with terminal myeloid differentiation [37]. The decreased TNAP synthesis is a classical feature of CML used as one of diagnostic cytochemical markers in differential diagnosis [2]. We have observed vitamin E targeted decrease in aberrant embryonic-like PLAP expression at mRNA level with increased TNAP mRNA expression. Moreover, along with down-regulation of aberrant PLAP the up-regulation of C/EBP alpha mRNA expression was restored by vitamin E in exposed K562 cells as we founded (Figure 1D and Table 2).
N(n=3) | Fold decreasing | Standard deviation, σ | Fold increasing | Standard deviation, σ | Fold increasing | Standard deviation, σ |
---|---|---|---|---|---|---|
PLAP(M ± m) | CEBPα(M ± m) | TNAP (M ± m) | ||||
1 | 4.088 ± 0.322 | 1.42 | 2.972 ± 1.594 | 1.35 | 6.023 ± 2.809 | 1.98 |
2 | 6.292 ± 1.883 | 4.377 ± 0.117 | 1.690 ± 1.524 | |||
3 | 2.848 ± 1.561 | 6.207 ± 1.713 | 1.931 ± 1.283 |
The relative fold decreasing PLAP corresponding to fold increasing CEBP α and TNAP mRNA expression (analyzed in triplicates) in gene expression in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
Taken together, we have concluded that the loss of TNAP and CEBP alpha in CML may contribute to pathogenesis of this disease whereas aberrant embryonic-like PLAP may be considered as a new CML biomarker of LSC pluripotent phenotype in CML progression. Therefore, aberrant embryonic-like PLAP may be considered as a putative target in differentiation therapies in myeloid neoplasms. Our findings suggest the biomodulation role of vitamin E as the available inducer of differentiation potential of CML leukemic cells. The ectopic PLAP expression in leukemic cells of different myeloid neoplasms suggests its importance in biology of these malignancies.
Conclusivelly, to analyze whether ectopic PLAP expression in CMLcells
To sum up, we have demonstrated increased aberrant PLAP expression in leukemic cells of myeloid origin (CML) in the setting of the decreased TNAP expression. The aberrant expression of embryonic PLAP may be considered as one of the putative markers of myeloid cell undifferentiated state. On the other hand, potential of PLAP as one of the possible target for controlling LSC phenotype should be further explored. More attention is needed to explore the potential of the bioactive molecules such as vitamin E that may induce granulopoiesis reprogramming.
The persistence of LSC remains a major obstacle to cure CML [38, 39]. Epithelial mesenchymal transition (EMT) mechanism is known to contribute to tumor stem cell progression [40, 41]. Although EMT has been studied in relation to epithelium-derived tumors, there is increasing evidence implicating the involvement of EMT activators in hematopoietic malignancies [42, 43]. The expression of some EMT modulators has been demonstrated in Ph + leukemia cells [44]. EMT inducer Snail if of most important role in maintaining stemness properties in tumor progression [45, 46]. It was shown that Snail also drives LSC phenotype in leukemia progression [44, 47]. Earlier, we revealed that alpha-tocopherol might be an effective inducer of mRNA CEBP alpha in K562 cells
We have determined the relationship between EMT-Snail suppression and restored CEBP alpha myeloid differentiation potential in CML blast crisis K562 cells exposed to vitamin E. Metformin as known substance mediating EMT reversal [49] was used to compare EMT suppression effect of vitamin E in K562 cells.
We have found highly detectable Snail1 mRNA expression and down-regulated CEBP alpha in K562 cells (Figure 1E). Vitamin E suppressed EMT-Snail mRNA expression and up-regulated myeloid master regulator CEBP alpha mRNA expression (Figure 1E and Tables 3, 4). Such reactivation of CEBP alpha is enhanced by metformin pointing to the possible synergistic effect with alpha-tocopherol. We observed that vitamin E is a modulator of gene expression that affects Snail1 and CEBP alpha mRNA expression in K562 cells in opposite directions. One could suggest the causal relationship between EMT-Snail1 suppression and restoration of CEBP alpha expression that seems to contribute to recover myeloid differentiation potential of CML blast cells. As seen in Figure 1E, myelopoietic master regulator C/EBPα is also restored upon metformin treatment, although the effect of vitamin E is more pronounced (Table 4).
N(n=3) | Fold decreasing | Standard deviation, σ | Fold decreasing | Standard deviation, σ |
---|---|---|---|---|
Vitamin E/Snail M ± m | Metformin/Snail M ± m | |||
1 | 14.160 ± 0.437 | 0.408 | 1.579 ± 0.110 | 0.086 |
2 | 13.176 ± 0.547 | 1.366 ± 0.103 | ||
3 | 13.833 ± 0.110 | 1.464 ± 0.005 |
Fold increase EMT-inducer transcription factor SNAIL mRNA expression (analyzed in triplicates) in gene expression in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
N(n=3) | Fold increasing | Standard deviation, σ | Fold increasing | Standard deviation, σ | Fold increasing | Standard deviation, σ |
---|---|---|---|---|---|---|
Vitamin E M ± m | Vitamin E + Metformin M ± m | Metformin M ± m | ||||
1 | 5.156 ± 0.328 | 0.232 | 5.564 ± 0.075 | 0.371 | 2.841 ± 0.007 | 0.272 |
2 | 4.634 ± 0.194 | 5.00 ± 0.489 | 3.164 ± 0.330 | |||
3 | 4.696 ± 0.132 | 5.902 ± 0.413 | 2.498 ± 0.336 |
The fold increase of relative levels of the transcription factor CEBP alpha mRNA expression compared with metformin (4 mM) under decreasing of relative levels of the transcription factor Snail mRNA expression by vitamin E (analyzed in triplicates) in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
Taken together, schematic model of the Vitamin E modulation effects in CML blast crisis progression with Snail-EMT phenotype is presented (Figure 2).
Schematic model of the vitamin E modulation in CML progression with EMT phenotype.
CML is characterized by an accelerated and unregulated proliferation of predominantly myeloid cells in the bone marrow with their accumulation in the blood. CML develops as a result of malignant transformation and clonal proliferation of pluripotent hematopoietic stem cells (HSCs), leading to overproduction of immature myeloid progenitor cells that results in blast cell crisis. The CML blast crisis resembles acute leukemia. Because the preeminent mutation driving CML is Bcr-ABL thyrosine kinase oncogene, the use of Bcr-Abl kinase inhibitors (TKIs), such as imatinib, dasatinib, and nilotinib, significantly improves treatment outcomes and extends the life expectancy of CML patients. However, imatinib resistance drives blast crisis progression. The persistence of LSCs remains a major obstacle to cure CML. The clinical CML blast crisis progression with LSC phenotype is practically incurable. Therefore, the blocking of terminal myeloid differentiation and LSC phenotype development defines a putatively new strategy for CML prevention.
The potential of vitamin E in regulation of these interdependent mechanisms in CML progression was hinted by several observations that were reported earlier. Sangodkar et al. [50] showed that vitamin E activates PP2A phosphatase resulting in Bcr-Abl thyrosine kinase inhibition and re-activation of myeloid differentiation pathway. In BCR/ABL transformed cells and CML blast crisis hematopoietic progenitors, the PP2A activity is strongly inhibited, while the pharmacological activation of PP2A suppresses BCL/ABL activity and induces BCR/ABL degradation [51]. The pharmacological modulation of PP2A activity is becoming an attractive strategy for cancer treatment. The substances of several different classes are known as PP2A activating compounds, vitamin E (α-tocopherol) and its analogues having been reported among such compounds [50, 52].
Nevertheless, the effects of vitamin E on differentiation pathways in cells of blast crisis CML, in particular those involving restoration of the expression of CCAAT-enhancer binding protein alpha (C/EBPα) and granulocyte colony-stimulating factor receptor (G-CSFR) have not been yet studied. The expression of these proteins decreases drastically in chronic phase and blast crisis of CML [53, 54]. In this regard, we evaluated the effect of vitamin E on RNA expression of crucial factors of myeloid differentiation, C/EBRα and G-CSFR, in BCR-ABL-positive CML blast crisis K562 cells. Our data demonstrate that vitamin E restores the expression of C/EBPα and concequently G-CSFR. Our results are consistent with Tavor et al. [23] who demonstrated that the restoration of C/EBPα expression in BCR-ABL-positive KCL22 blast cell line triggered a proliferative arrest, a block in the G2/M phase of the cell cycle and a gradual increase in apoptosis suggesting the activation of differentiation. Therefore, C/EBPα stimulated by vitamin E may be considered as a putative target in differentiation therapies in myeloid leukemias.
The second effect of vitamin E potentially useful for CML treatment was reported by Nieborowska-Skorska et al. [55] who demonstrated that vitamin E prevents accumulation of imatinib-resistant BCR-ABL1 kinase mutations in mice CML xenografts. The authors stressed anti-oxidant function of vitamin E in this processes. We use vitamin E as modulating factor in CML that involves vitamin E-dependent EMT mechanism of repression taking into account the pivotal role of EMT in the development of LSC phenotype. In this connection, we observed Snail1 overexpression suggesting some features of EMT phenotype in K562 cells seemingly contributing to CML pathogenesis. Furthermore, we have determined down-regulation of CEBP alpha transcription factor representing the master regulator of myelopoiesis in CML cells coinciding with Snail1 overexpression. Our findings are quite consistent with the recent report by Lourenço et al. [43] who suggest that C/EBP α is crucial determinant of epithelial maintenance by preventing EMT. Indeed, we have found that CEBP alpha is repressed by overexpression of EMT-inducer Snail in CML blast crisis K562 cells. Consequently, the reactivation of CEBP alpha by vitamin E is paralleled by suppression of Snail.
Therefore, our findings make deeper understanding of the role of vitamin E in suppression of CML LSC phenotype. In addition, we have revealed a new marker – aberrant placental-like alkaline phosphatase (PLAP) that expressed ectopically in CML progression. Moreover, its suppression by vitamin E consequently re-activates CEBP alpha and TNAP as myeloid differentiation factors. Taken together, our findings presented in this Chapter stress the role of vitamin E in modifying expression profile of CML cells towards restoration of myeloid differentiation potential.
Vitamin E is a complex group of lipid-soluble antioxidants comprising four tocopherols and four tocotrienols. It prevents production of reactive oxygen species (ROS) that are elevated in majority of tumor cells leading to lipid peroxydation, changing signaling pathways that control cell proliferation and apoptosis, expression of several transcription factors, epigenetic modulators, resistance to treatment, etc. We have suggested the causal relationship between EMT-Snail1 suppression and restoration of CEBP-alpha myeloid master regulator expression that seems to contribute to recover myeloid differentiation potential of CML blast cells by vitamin E. We first observed that vitamin E is an effective modulator of down-regulation of transcription factor Snail EMT-inducer and up-regulation of pivotal myelopoietic transcription factor CEBP alpha resulting in restoration of TNAP expression. Taken into account the data of literature and our findings, we can postulate that vitamin E might be used as a potential pharmacopoeian biological modulator capable of preventing the onset of blast crisis development, ameliorating disease progression and possibly overcoming drug resistance of leukemic cells in CML patients.
All authors of chapter are Laureates of the National Award of the Cabinet of Ministers of Ukraine for the development and implementation of innovative technologies in the field of Biomedicine (N289.p from May 10, 2018).
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