Sectoral vulnerability in food, land and biodegradation in sub-continents of Asia.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"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:"5989",leadTitle:null,fullTitle:"Ubiquitination Governing DNA Repair - Implications in Health and Disease",title:"Ubiquitination Governing DNA Repair",subtitle:"Implications in Health and Disease",reviewType:"peer-reviewed",abstract:"DNA damage response (DDR) and lesion repair are vital processes ensuring genome integrity through various pathways depending mainly on the nature of DNA injury and cell cycle stage. DDR is finely regulated at many levels in co-ordination with other ongoing processes as is genome replication and cell cycle progression. Posttranslational modifications (PTMs), affecting both protein-protein and protein-DNA interactions, play a crucial role in finely tuning all processes involved in the restoration of genome lesions. Regarding damaged chromatin, PTMs serve in many cases as recruitment platforms for DNA repair mechanisms by facilitating binding sites or regulating interactions between involved proteins. Ubiquitination, the addition of ubiquitin moieties on a target protein, apart from controlling protein availability through degradation, is also involved, together with partner small ubiquitin-like modifier (SUMO), in controlling many pathways involved in DDR by modifying the structure-function relationship and thus interacting with partner molecules. The aim of this book is to cover a broad spectrum of current topics in ubiquitination and to a lesser extent SUMOylation involvement in regulation of DDR and repair in health and disease. This book is intended for pre- and postgraduate students and young scientists in this field. Members of both academic and research institutions, actively involved in the field, have described their current understanding of major mechanisms involved, highlighted key events, described ongoing applications in both developmental diseases and cancer and provided hints for future potential applications.",isbn:"978-1-78923-585-2",printIsbn:"978-1-78923-584-5",pdfIsbn:"978-1-83881-264-5",doi:"10.5772/66565",price:119,priceEur:129,priceUsd:155,slug:"ubiquitination-governing-dna-repair-implications-in-health-and-disease",numberOfPages:220,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"d9892e3c8d2c928119619d7425c9e371",bookSignature:"Effrossyni Boutou and Horst-Werner Stürzbecher",publishedDate:"August 1st 2018",coverURL:"https://cdn.intechopen.com/books/images_new/5989.jpg",numberOfDownloads:11415,numberOfWosCitations:4,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:7,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:13,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 13th 2016",dateEndSecondStepPublish:"December 22nd 2016",dateEndThirdStepPublish:"September 16th 2017",dateEndFourthStepPublish:"October 16th 2017",dateEndFifthStepPublish:"December 16th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"58579",title:"Dr.",name:"Effrossyni",middleName:null,surname:"Boutou",slug:"effrossyni-boutou",fullName:"Effrossyni Boutou",profilePictureURL:"https://mts.intechopen.com/storage/users/58579/images/4577_n.jpg",biography:"PhD in Molecular Biology & Biochemistry (Athens University). Research Interests on DNA repair mechanisms, Stem cell biology, Human Genetics.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Laiko General Hospital of Athens",institutionURL:null,country:{name:"Greece"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"201634",title:"Dr.",name:"Horst-Werner",middleName:null,surname:"Stürzbecher",slug:"horst-werner-sturzbecher",fullName:"Horst-Werner Stürzbecher",profilePictureURL:"https://mts.intechopen.com/storage/users/201634/images/7705_n.jpg",biography:"Prof. Dr. Horst-Werner Stuerzbecher is currently working in molecular cancer pathology as a professor at the Institute of Pathology, University Clinic of Schleswig-Holstein Campus Luebeck in Germany.\nAfter his studies in biology at the Westfaelische-Wilhelms University Muenster, Germany, he obtained his PhD (Dr. rer. biol. hum.) degree from the Department of Biochemistry at the University of Ulm, Germany. \nBetween 1986 and 1991, Prof. Stuerzbecher continued his research activities at the Marie-Curie Research Institute in Oxted, Surrey, UK, focusing on the tumor suppressor p53. He habilitated in genetics at the Institute of Genetics of the Johannes-Gutenberg University in Mainz, Germany, in 1992 and was appointed as a senior scientist at the Department of Tumor Virology of the Heinrich-Pette Institute in Hamburg, Germany. Prof. Stuerzbecher received a Heisenberg stipend from Deutsche Forschungsgemeinschaft (DFG) to lead his own research group at the Heinrich-Pette Institute focusing on the contribution of DNA repair processes to carcinogenesis, especially the interaction of the tumor suppressor protein p53 and the human RAD51 recombination protein.\nIn 1996, he accepted a position as professor of Genetics at the Institute of Human Genetics of the University Clinic of Schleswig-Holstein Campus Luebeck, Germany.\nIn addition to his work as a reviewer for various international journals and research grants, Prof. Stuerzbecher was also a coordinator of national and international research projects, for example, an international research project within the 5th Framework European Union.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"913",title:"Proteomics",slug:"structural-biology-proteomics"}],chapters:[{id:"58366",title:"Ubiquitylation and SUMOylation: An Orchestrated Regulation During DNA Damage Repair",doi:"10.5772/intechopen.72583",slug:"ubiquitylation-and-sumoylation-an-orchestrated-regulation-during-dna-damage-repair",totalDownloads:1038,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"DNA double-strand breaks (DSBs) are cytotoxic DNA lesions that must be repaired as soon as possible because it can cause chromosomal aberrations and cell death. Homologous recombination (HR) and nonhomologous end joining (NHEJ) are the pathways that mainly repair these ruptures. HR process is finely regulated by synchronized posttranslational modifications including phosphorylation, ubiquitylation, and SUMOylation. The ubiquitin (Ub) modifications at damaged chromatin serve as recruitment platforms for DSB repair complexes by facilitating binding sites or regulating the interaction between proteins. Thus, SUMOylation has been associated with protein interaction, enzymatic activity, and chromatin mobility. Several DNA damage factors have been found to be ubiquitylated and SUMOylated including histones (H2AX) and proteins such as Mre11, Rad51, NBS1, and BRCA1. Regarding ubiquitylation-mediated regulation of DNA repair, RNF168 and RNF8 E3 ligases have turned out to be a key step in DNA damage repair regulation. Interestingly, there is evidence that the Ub signaling mechanism is ancestral, and this emphasizes its importance.",signatures:"Sara Espinoza-Corona, Ma Luisa Bazán-Tejeda, Ulises Omar García-\nLepe and Rosa Ma Bermúdez-Cruz",downloadPdfUrl:"/chapter/pdf-download/58366",previewPdfUrl:"/chapter/pdf-preview/58366",authors:[{id:"205238",title:"Dr.",name:"Rosa",surname:"Bermudez",slug:"rosa-bermudez",fullName:"Rosa Bermudez"},{id:"207883",title:"MSc.",name:"Sara",surname:"Espinoza-Corona",slug:"sara-espinoza-corona",fullName:"Sara Espinoza-Corona"},{id:"207884",title:"Dr.",name:"Maria Luisa",surname:"Bazan-Tejeda",slug:"maria-luisa-bazan-tejeda",fullName:"Maria Luisa Bazan-Tejeda"},{id:"207885",title:"BSc.",name:"Ulises Omar",surname:"Garcia-Lepe",slug:"ulises-omar-garcia-lepe",fullName:"Ulises Omar Garcia-Lepe"}],corrections:null},{id:"57498",title:"The Five Families of DNA Repair Proteins and their Functionally Relevant Ubiquitination",doi:"10.5772/intechopen.71537",slug:"the-five-families-of-dna-repair-proteins-and-their-functionally-relevant-ubiquitination",totalDownloads:941,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The process of DNA repair, be it a response to replication dysfunction or genotoxic insult, is critical for the resolution of strand errors and the avoidance of DNA mismatches that could result in various molecular pathologies, including carcinogenic development. Here, we will describe the five main mechanisms by which DNA avoids mutation, namely the processes of base excision repair, mismatch repair, nucleotide excision repair, homologous recombination, and nonhomologous end joining. In particular, we will dissect the functional significance of various posttranslational modifications of the essential proteins within these pathways, including but not limited to ubiquitination, acetylation, and phosphorylation.",signatures:"Niko Moses and Xiaohong Mary Zhang",downloadPdfUrl:"/chapter/pdf-download/57498",previewPdfUrl:"/chapter/pdf-preview/57498",authors:[{id:"202135",title:"Ph.D.",name:"Xiaohong",surname:"Zhang",slug:"xiaohong-zhang",fullName:"Xiaohong Zhang"},{id:"203639",title:"Ms.",name:"Niko",surname:"Moses",slug:"niko-moses",fullName:"Niko Moses"}],corrections:null},{id:"56957",title:"Regulation of the Base Excision Repair Pathway by Ubiquitination",doi:"10.5772/intechopen.70733",slug:"regulation-of-the-base-excision-repair-pathway-by-ubiquitination",totalDownloads:1041,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Genome integrity is under constant threat from cellular reactive oxygen species generated by endogenous and exogenous mutagens. The base excision repair (BER) pathway consequently plays a crucial role in the repair of DNA base damage, sites of base loss and DNA single strand breaks that can cause genome instability and ultimately the development of human diseases, including premature ageing, neurodegenerative disorders and cancer. Proteins within the base excision repair pathway are increasingly being found to be regulated and controlled by post-translational modifications, and indeed ubiquitination performs a key role in the maintenance of repair protein levels but may also impact on protein activity and cellular localisation. This process is therefore important in maintaining an efficient cellular DNA damage response, and if not accurately controlled, can cause DNA damage accumulation and promote mutagenesis and genomic instability. In this chapter, we will present up-to-date information on the evidence of ubiquitination of base excision repair proteins, the enzymes involved and the molecular and cellular consequences of this process.",signatures:"Rachel Jane Carter and Jason Luke Parsons",downloadPdfUrl:"/chapter/pdf-download/56957",previewPdfUrl:"/chapter/pdf-preview/56957",authors:[{id:"203604",title:"Dr.",name:"Jason",surname:"Parsons",slug:"jason-parsons",fullName:"Jason Parsons"},{id:"207678",title:"Dr.",name:"Rachel",surname:"Carter",slug:"rachel-carter",fullName:"Rachel Carter"}],corrections:null},{id:"58796",title:"The Role of Deubiquitinases in DNA Double-Strand Break Repair",doi:"10.5772/intechopen.73341",slug:"the-role-of-deubiquitinases-in-dna-double-strand-break-repair",totalDownloads:969,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"DNA double-strand break (DSB) is a type of the most critical DNA lesions, and if not repaired promptly, it can result in cell death or a wide variety of genetic alterations including genome instability, large- or small-scale deletions, chromosome loss, loss of heterozygosity, and translocations. DSBs are repaired by double-strand break repair (DSBR), including nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathway, and defects in these pathways cause genome instability and promote tumorigenesis. Accumulating evidence has demonstrated that the superfamily of deubiquitinases (DUBs) can regulate the action and stability of DNA repair enzymes involving in DSBR via modifying ubiquitination levels, a reversible posttranslational modification pathway. In this review, we will discuss ubiquitination/deubiquitination modification involving in DSBR genes, the role of DUBs in DSBR and corresponding mechanisms, and the potential effects of this modification on human diseases.",signatures:"Jun Lu, Zhi-Feng Xi, Xiao-Ying Huang, Qiang Xia and Xi-Dai Long",downloadPdfUrl:"/chapter/pdf-download/58796",previewPdfUrl:"/chapter/pdf-preview/58796",authors:[{id:"202142",title:"Prof.",name:"Xi-Dai",surname:"Long",slug:"xi-dai-long",fullName:"Xi-Dai Long"},{id:"202476",title:"Prof.",name:"Qiang",surname:"Xia",slug:"qiang-xia",fullName:"Qiang Xia"},{id:"204289",title:"Dr.",name:"Jun",surname:"Lu",slug:"jun-lu",fullName:"Jun Lu"},{id:"204290",title:"Dr.",name:"Zhi-Feng",surname:"Xi",slug:"zhi-feng-xi",fullName:"Zhi-Feng Xi"}],corrections:null},{id:"56818",title:"The Roles of Cullin RING Ligases and the Anaphase Promoting Complex/Cyclosome in the Regulation of DNA Double Strand Break Repair",doi:"10.5772/intechopen.70482",slug:"the-roles-of-cullin-ring-ligases-and-the-anaphase-promoting-complex-cyclosome-in-the-regulation-of-d",totalDownloads:1005,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Historically, genome maintenance has been viewed as the largely independent activities of (1) ubiquitin ligases driving unidirectional cell cycle progression and, (2) the activity of cellular checkpoints that monitor DNA integrity and DNA replication. It is well established that the DNA damage response (DDR) checkpoint machinery promotes the activation of repair mechanisms in addition to opening a window for repair. Emerging evidence demonstrates an integrated network of the central cell cycle driving E3 ubiquitin ligases and the checkpoint machinery, as well as deubiquitinating enzymes, which intermittently cooperate and antagonize one another to define windows of checkpoint and repair activities to optimize genome stability and cellular health. A growing number of components of the ubiquitin machinery are involved in the DDR. Herein, we focus on the regulation of cell cycle checkpoints and the DNA repair mechanisms for double strand breaks (DSBs) by the coordinated activities of Cullin RING ligases (CRLs) and the anaphase promoting complex/cyclosome (APC/C).",signatures:"Debjani Pal and Matthew K. Summers",downloadPdfUrl:"/chapter/pdf-download/56818",previewPdfUrl:"/chapter/pdf-preview/56818",authors:[{id:"204371",title:"Associate Prof.",name:"Matthew",surname:"Summers",slug:"matthew-summers",fullName:"Matthew Summers"},{id:"208322",title:"Dr.",name:"Debjani",surname:"Pal",slug:"debjani-pal",fullName:"Debjani Pal"}],corrections:null},{id:"57410",title:"The Cross Talk among Autophagy, Ubiquitination, and DNA Repair: An Overview",doi:"10.5772/intechopen.71404",slug:"the-cross-talk-among-autophagy-ubiquitination-and-dna-repair-an-overview",totalDownloads:1287,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Cellular plasticity is modulated by protein posttranslational modifications, which act on most intracellular pathways. Ubiquitination is a versatile posttranslational modification (PTM) that influences protein fate, controlling their degradation or modulating their activity and subcellular localization. The ubiquitin proteasome system, UPS, and the autophagic pathway are the main degradative intracellular machineries, which rely on ubiquitination for their activation and/or the selective recycling of proteins and organelles. Recent findings indicate that the cross talk between UPS and autophagy plays a key role in controlling DNA repair pathways. Even being a cytoplasmic process, it is now clear that autophagy can directly impact on the correct activation of DNA repair. Of note, defects on autophagy are related to the impairment of homologous recombination repair and to an increase of the nonhomologous end joining repair activity. These evidences give new insights into the molecular processes underlying the DNA damage response and provide further explanation for the tumorigenesis associated with autophagy impairment. Moreover, these findings introduce new examples of synthetic lethality between autophagy and DNA repair genes and lead to the possible development of target therapies for tumors with defective autophagy.",signatures:"Francesca Nazio, Emiliano Maiani and Francesco Cecconi",downloadPdfUrl:"/chapter/pdf-download/57410",previewPdfUrl:"/chapter/pdf-preview/57410",authors:[{id:"204392",title:"Prof.",name:"Francesco",surname:"Cecconi",slug:"francesco-cecconi",fullName:"Francesco Cecconi"},{id:"204393",title:"Dr.",name:"Emiliano",surname:"Maiani",slug:"emiliano-maiani",fullName:"Emiliano Maiani"},{id:"204394",title:"Dr.",name:"Francesca",surname:"Nazio",slug:"francesca-nazio",fullName:"Francesca Nazio"}],corrections:null},{id:"62505",title:"Interlace between Chromatin Structure, DNA Repair and Ubiquitination",doi:"10.5772/intechopen.77175",slug:"interlace-between-chromatin-structure-dna-repair-and-ubiquitination",totalDownloads:889,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Chromatin remodeling, ubiquitylation, and DNA damage repair may be regarded as three discrete processes, but in fact, they are three extremely important interlinked processes that are imperative for the sustenance for life. Discrepancies in one will have outcomes that will affect the other processes direly. Exogenous and endogenous factors persistently affect the DNA by inducing damage and modifications. To sustain the integrity of life, these challenges need to be combated efficiently. For the preservation of the structural and functional components of the genome, nature has allowed them to evolve numerous pathways that constantly work to repair the induced damage. This sort of response is termed as DDR (DNA damage response) that include BER and NER (base excision and nucleotide excision repair, respectively) and non-homologous end joining and homologous recombination (NHEJ & HR). Since the DNA in cells is exceedingly organized and compressed, hence any process that utilizes DNA as its substrate requires essential remodeling of the chromatin structure. The chapter emphasizes on the phenomenon of chromatin remodeling and ubiquitylation which subsequently affects the integral process of DNA damage repair.",signatures:"Attya Bhatti, Shanzay Ahmed, Arooma Jannat and Peter John",downloadPdfUrl:"/chapter/pdf-download/62505",previewPdfUrl:"/chapter/pdf-preview/62505",authors:[{id:"219185",title:"Ph.D.",name:"Attya",surname:"Bhatti",slug:"attya-bhatti",fullName:"Attya Bhatti"}],corrections:null},{id:"62195",title:"Maintenance of Genome Stability by Ubiquitination of DNA Repair Proteins in Mammalian Development and Disease",doi:"10.5772/intechopen.79244",slug:"maintenance-of-genome-stability-by-ubiquitination-of-dna-repair-proteins-in-mammalian-development-an",totalDownloads:1007,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"To maintain genome DNA, DNA repair machinery has been developed in cellular life cycle. Multiple DNA repair pathways such as base excision repair, nucleotide excision repair, DNA cross link damage repair, DNA single strand break repair and DNA double strand break repair including nonhomologous end joining and homologous recombination are regulated by protein signal cascade. Because of limited gene number, protein posttranslational modification signal has advantage to control cell dynamics during development and senescence. This chapter focuses on how DNA repair proteins molecular modification including phosphorylation and ubiquitination contribute to genome stability pathway during mammalian development and disease.",signatures:"Mikio Shimada",downloadPdfUrl:"/chapter/pdf-download/62195",previewPdfUrl:"/chapter/pdf-preview/62195",authors:[{id:"42943",title:"Dr.",name:"Mikio",surname:"Shimada",slug:"mikio-shimada",fullName:"Mikio Shimada"}],corrections:null},{id:"57018",title:"Ubiquitination and DNA Repair in Multiple Myeloma",doi:"10.5772/intechopen.70800",slug:"ubiquitination-and-dna-repair-in-multiple-myeloma",totalDownloads:1118,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells in the bone marrow. MM cells are characterized by genomic abnormalities that arise during the pathogenesis of disease and accumulate during progression. DNA repair pathways are critical to repair the plethora of DNA lesions that occur in MM, and deregulation of these pathways is implicated in disease onset and survival. The ubiquitin proteasome system has emerged as a central player in the regulation of DNA damage response (DDR). In this chapter, we review defects within the ubiquitin proteasome system that are associated with abnormal DNA damage response in MM and discuss current and potential novel ways of targeting these aberrations in the clinic.",signatures:"Lisa J. Crawford and Alexandra E. Irvine",downloadPdfUrl:"/chapter/pdf-download/57018",previewPdfUrl:"/chapter/pdf-preview/57018",authors:[{id:"88220",title:"Dr.",name:"Alexandra",surname:"Irvine",slug:"alexandra-irvine",fullName:"Alexandra Irvine"},{id:"202927",title:"Dr.",name:"Lisa",surname:"Crawford",slug:"lisa-crawford",fullName:"Lisa Crawford"}],corrections:null},{id:"61321",title:"Ubiquitin and Fanconi Anemia",doi:"10.5772/intechopen.77123",slug:"ubiquitin-and-fanconi-anemia",totalDownloads:1008,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Fanconi anemia (FA) is an inherited disease distinct from the failure of bone marrow, growth disturbance, predisposition to cancer and concomitant chromosomal abnormalities. FA is associated with genes involved in DNA replication and DNA repair processes. More than 20 proteins have been identified to be related with FANC pathway operation. Necessary prerequisite for activation and regulation of FA pathway is the monoubiquitination of heterodimer FANCD2-FANCI by core proteins of Fanc complex. The monoubiquitination of FANCD2-FANCI is crucial for nuclear localization of heterodimer, binding to chromatin and regulation of DNA repair procedure. Mutations of genes of FANC complex proteins associated with deficiency of DNA repair pathways affected cellular and genome instability. The interaction between proteins and ubiquitination affected genomic integrity and stability.",signatures:"Ioannis Drikos and Alexandros Sachinidis",downloadPdfUrl:"/chapter/pdf-download/61321",previewPdfUrl:"/chapter/pdf-preview/61321",authors:[{id:"204419",title:"Dr.",name:"Ioannis",surname:"Drikos",slug:"ioannis-drikos",fullName:"Ioannis Drikos"}],corrections:null},{id:"59607",title:"Review of the Ubiquitin Role in DNA Repair and Tumorigenesis, with Emphasis in Breast Cancer Treatment; Current Data and Future Options",doi:"10.5772/intechopen.72600",slug:"review-of-the-ubiquitin-role-in-dna-repair-and-tumorigenesis-with-emphasis-in-breast-cancer-treatmen",totalDownloads:1117,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Breast carcinoma remains the commonest carcinoma among women worldwide. Despite the fact that impressive progression has been achieved so far regarding pathophysiology, histopathology and treatment of this cancer, there are still undiscovered fields on molecular and therapeutic levels. The need of resolving problems such as chemoresistance, recurrence and metastasis has led in revealing key molecules in the development and progression of malignancies, including breast tumors. In this review, we will briefly describe the functions of ubiquitin and post-translational modifications (PTMs) focusing specially in DNA repair and then discuss about the implication of ubiquitin and related molecules in tumorigenesis and specifically in breast carcinoma. So far there are only few drugs approved by FDA that target the ubiquitin system. There will be an analysis regarding the current and potential anti-cancer therapeutic strategies based on targeting specific ubiquitin-related molecules.",signatures:"Despoina Mourtzoukou, Ioannis Drikos, Nikolaos Goutas and\nDimitris Vlachodimitropoulos",downloadPdfUrl:"/chapter/pdf-download/59607",previewPdfUrl:"/chapter/pdf-preview/59607",authors:[{id:"204926",title:"Dr.",name:"Dimitris",surname:"Vlachodimitropoulos",slug:"dimitris-vlachodimitropoulos",fullName:"Dimitris Vlachodimitropoulos"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"780",title:"Proteomics",subtitle:"Human Diseases and Protein Functions",isOpenForSubmission:!1,hash:"a90c4e5b369d27036134a3c66ce1cb26",slug:"proteomics-human-diseases-and-protein-functions",bookSignature:"Tsz-Kwong Man and Ricardo J. 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\r\n\tCartilage lesions of the knee are common and should be treated correctly if symptomatic. Until now, multiple (surgical) techniques have been described; however, there is no consensus on which one should be used. Also, treatment techniques using platelet-rich plasma, mesenchymal stem cells, and different king of growth hormones have been mentioned. In this book, the importance of other knee structures when treating these knee cartilage defects will be discussed as the meniscus, integrity of ligaments, and the importance of the alignment of the lower limb will be emphasized. The book will give an update on the different treatment approaches in knees with this (osteo-)chondral lesion.
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Dr. Almqvist is an editorial board member at Sage Journals, Affiliated with the Orthocure Clinic, Dubai as an Orthopedic Consultant, Mediclinic City Hospital as a Consultant Orthopaedic surgeon, and is a member of ISAKOS.",coeditorOneBiosketch:"Dr. El Hamaky is a practitioner with over 11 years of experience in Orthopedic Surgery, is a member of the Egyptian Board of Orthopedic Surgery, a member of the AO Foundation, and was awarded his medical degree from the University of Cairo.",coeditorTwoBiosketch:"Dr. Taiceer Abdulwahab is an experienced practitioner, specializing in orthopedic surgery, trauma, and sports medicine, previously affiliated with The University of Bristol, The University of Edinburgh, The University of Warwick, and The University of Leicester, and is a member of the Royal College of Surgeons (MRCS) London, UK.",coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"251312",title:"Dr.",name:"Karl",middleName:null,surname:"Almqvist",slug:"karl-almqvist",fullName:"Karl Almqvist",profilePictureURL:"https://mts.intechopen.com/storage/users/251312/images/system/251312.jpg",biography:"Prof. Dr. Almqvist trained at the University of Ghent in Belgium and worked at the Ghent University Hospital where he was Head of Clinic, Department of Physical Medicine and Orthopaedic Surgery, prior to moving to Dubai in 2014. He also has considerable teaching experience and is an assistant professor in Physiotherapy and Orthopaedic Surgery at Ghent University. Karl Fredrik has published extensively and written a number of book chapters. He is a regular speaker at international meetings and is on the editorial board or is a reviewer for the major sports orthopedic journals.\r\nHe obtained his Ph.D. in 2001 (Human differentiated articular cartilage cells in biodegradable matrices – Preparative studies for their use in the repair of cartilage defects).\r\nKarl Fredrik is active in a number of orthopaedic organisations, and is the past Chairman of the Sports Committee of the International Society of Arthroscopy, Knee Surgery & Orthopaedic Sports Medicine as well as the past Chairman of the Cartilage Committee of the European Society of Sports Traumatology, Knee Surgery & Arthroscopy.\r\nThe main area of interest Karl Fredrik is knee surgery. 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He is also an Assistant Clinical Professor of Orthopaedic Surgery at Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai.\r\nHe is a Master of Surgery (ChM) in Trauma & Orthopaedic Surgery, degree obtained at the University of Edinburgh School of Medicine in partnership with the Royal College of Surgeons of Edinburgh, UK. He received his Master of Science (MSc) in Trauma & Orthopaedic Surgery degree from Warwick School of Medicine, University of Warwick, UK. He also received a Postgraduate Award (PGA) in Understanding Research & Critical Appraisal at the Warwick School of Medicine, University of Warwick, UK.\r\nDr. Abdulwahab obtained his primary medical qualification, Bachelor of Medicine & Bachelor of Surgery (MBChB) from the Bristol School of Medicine, University of Bristol, UK.\r\nDr. Taiceer Abdulwahab is a Member of the Royal College of Surgeons of England (MRCS).\r\nHe has presented at various international conferences including the International Congress for Joint Arthroplasty (ICJR) and the European College of Sports & Exercise Physicians (ECOSEP) with FIFA update, as well as published in peer-reviewed journals, Editor for a book titled 'Meniscus of the Knee', and investigator in several randomized controlled trials.\r\nHe is Trauma Doctor for the annual Emirates Rugby 7s.\r\nHe has a special interest in Sports Surgery (Arthroscopic Shoulder and Knee surgery).",institutionString:"Mediclinic City Hospital",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Mediclinic City Hospital",institutionURL:null,country:{name:"United Arab Emirates"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"466998",firstName:"Dragan",lastName:"Miljak",middleName:"Anton",title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/466998/images/21564_n.jpg",email:"dragan@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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The regulatory RNA molecules include small interfering RNAs (siRNAs), and short hairpin RNAs (shRNAs) provide the specific degradation of target mRNA in mammalian cells [1]. siRNAs are the products of long double-stranded RNA (dsRNA) molecules in cells, which are expressed transgenically or delivered exogenously. Synthetic siRNAs can be transfected into cells that specifically silence the expression of target genes. In the RNAi pathway, dsRNA (over 100 nt) molecules are cleaved into 21- to 23-nucleotide duplexed RNAs, termed as siRNA duplex, by endoribonuclease Dicer or RNAse III-type enzyme. The cleaved siRNA duplexes contain 5′-phosphate and two-base 3′ overhangs. siRNAs are incorporated into the endogenous RNA-induced silencing complex (RISC). One of the two strands of siRNA duplex is guide (antisense) strand, and the other is passenger (sense) strand. siRNA duplex is unwinded by RNA helicase activity. While the guide strand binds to the RISC, the passenger strand is degraded. The activated RISC binds to mRNA with base-pairing for sequence-specific degradation of complementary mRNA. The mRNA fragments cleaved by Argonaute (Ago) proteins are released from RISC and degraded by other endogenous nucleases. After mRNA degradation, the active RISC is rebuilt and can participate in another RNAi pathway [2, 3]. In the event, RNAi process decreases specific mRNA levels, and thus decreases target gene expression.
Among the nucleic acid–based drugs, siRNAs as potential novel drug candidates are offered a highly promising strategy in cancer therapy. The knockdown of abnormal gene overexpression, occuring in cancer by using siRNA, has been used in therapeutic applications [2]. Targets of chemical drugs are limited to certain classes of receptors, ion channels, and enzymes. In the treatment with siRNA, known sequence of any gene of interest is sufficient and its target choice is unlimited [4].
The potential advantages of siRNA treatment compared with other treatment methods are that siRNAs [5–7] (i) provide sequence-specific gene therapy; (ii) can specifically target many undruggable genes or downregulate gene products; (iii) are considered the safe therapeutics; (iv) are potent and efficient molecules and possess high gene silencing activity; and (iv) can be easily designed for any disease.
RNAi might be a promising new pharmaceutical area for treatment of incurable and severe diseases such as cancers and infections. RNAi applications have been recently achieved by using synthetic siRNAs and vector-based siRNA expression systems or short hairpin RNAs (shRNAs) synthesized within the cells by vector-mediated production. The expressed shRNAs from plasmid and viral vectors in nucleus are cleaved by Dicer in cytoplasm and siRNAs are formed. There both strategies have advantages and disadvantages. Vector-based siRNA expression systems have several advantages for applying RNAi compared to synthetic siRNAs. Both permanent and transient transfection with vector-based systems can be achieved, and thus vector-based system increases the period of siRNA-mediated inhibition of gene expression [8]. In addition, shRNA constructs are more stable than siRNAs [9]. Low amount (nM) of siRNA and less than five copies of shRNA are sufficient for stable transfection and for acheiving gene silencing effect [10]. The synthetic siRNAs can be easily synthesized in large amounts and chemically modified to improve stability, permeability, efficacy, and transfection control; however, the modified siRNAs are highly expensive [11]. siRNAs are not integrated into host genome. The modification of vector-based shRNA systems is difficult, but shRNA expression systems can be regulated or induced by appropriate promoters and termination sequences. Choice of promoter, loop structure of shRNA, length and arrangement of sense and antisense strands, and orientation of restriction enzyme regions are important for shRNA expression cassette preparation. Similar to the various RNAi applications for targeted gene silencing, the chimeric expression cassettes of siRNA and shRNA in the same expression unit might also be made [12].
Design of optimal siRNA sequence plays a key role for successful siRNA therapy. The choice of potent and specific siRNA sequences is important for minimization of immune responses and off-target effects. siRNAs are 19–27 base pairs in length, but mostly preferred to be 21 nt of siRNAs with a structure of 19 nt duplex region and two nucleotide overhangs at the 3′ end, usually TT and UU, which are important for recognition by the RNAi machinery. Increasing the length of the dsRNA may enhance its potency, dsRNAs with 27 nucleotides are up to 100 times more potent than the siRNAs containing 21 nucleotides. The longer (25–30 nt) duplexes act as a substrate for Dicer (Dicer-subtrate siRNAs). This Dicer-substrate siRNAs are more efficiently loaded into the RISC over the siRNAs with 21 bp and newly produced siRNAs from the long dsRNAs directly incorporated into the RISC complex. Thus, gene silencing mechanism can be facilitated [13, 14]. On the other hand, dsRNAs longer than about 30 bp can lead to interferon response, which is the defense mechanism against viral infection. The activation of interferon pathway causes non-specific mRNA degradation and apoptosis [15, 16]. The long dsRNAs activates innate immune response by interaction with protein kinase receptor (PKR) and Toll-like receptors (TLR7 and 8 are activated by ssRNA; TLR9 activated by unmethylated CpG; and TLR3 activated by dsRNA). The activation of these receptors induces interferon (IFN) and proinflammatory cytokines [10, 17].
In addition to immune responses, another important problem for efficient RNAi therapy is off-target effects of these molecules. The cause of off-target effects are the suppression of undesired or unpredicted genes other than the desired target genes. The absence of homolog sequences between siRNA and its target mRNA can cause cleavage of non-targeted mRNA regions. Off-target effects of siRNA can lead to problems in the interpretation of gene silencing studies, serious and unwanted side effects such as potential toxicity and even cell death [18]. There are many factors and mechanisms leading to occurence of off-target effects. These factors are the length of dsRNA or siRNA, the length and position of siRNA-target sequence mismatch, and coding sequences and untranslated regions in genes [19]. The mechanisms leading to off-target effects of siRNAs are (i) the regulation of unwanted transcripts by seed sequence homology to the 3′ UTR of cellular mRNAs, (ii) the saturation of RISC by affecting cellular miRNA activity of siRNAs in large amounts, (iii) the function of miRNAs as siRNAs or shRNAs because of similarities in gene silencing pathway, (iv) non-specific distribution by non-targeting systemic delivery, and (v) immunostimulatory motifs in siRNA sequences [14, 17, 20].
Many preclinical studies with siRNA indicated that it is a hopeful molecule for clinical research of various diseases. Up to date, at least 22 RNAi-based drugs have been evaluated in clinical trials [21]. The first clinical trial with siRNA was made in 2004 by Opko Health. The clinical studies of Bevasiranib, that is, siRNA targeting vascular endothelial growth factor (VEGF) to suppress ocular neovascularization in patients with age-related macular degeneration (AMD), continued to the phase III trial, but the clinical trials was terminated in 2009 because of its poor efficacy and causing vision loss. Allergan company has terminated the phase II clinical trials of siRNA AGN-745, targeting VEGF because of its off-target effects [21]. The clinical translation of RNAi can be possible with development of safe and efficient RNAi delivery systems that lack of off-target effects [7, 21].
Although siRNAs are used as the potential therapeutic molecules in cancer and other diseases, the most important challenge in the development of RNAi-based drugs is efficient and safe delivery of appropriate doses to target cells and tissues. Therefore, the development of siRNA-based viral and non-viral delivery systems are required to have an enhanced efficacy, improved stability, and minimized non-specific gene silencing such as off-target effects and immune responses. This chapter focuses on recent improvements in the non-viral siRNA delivery systems in cancer therapy.
Cancer is a multistep genetic disease, which develops as a consequence of changes in the control of cell proliferation and differentiation. In the transformation of normal cells to tumor cells, the affected cells undergo mutations such as downregulation of tumor suppressor genes and overexpression of oncogenes. RNAi-based therapeutics have been extensively used for knockdown of cancer-associated genes. The
Cancer cells have the ability to develop a resistance to chemotherapeutic drugs. RNAi-based therapeutics can simultaneously target multiple genes in cancer signaling pathway. The simultaneous silencing of multiple genes in cancer therapy have importance in terms of minimizing the multiple drug resistance caused by small chemical molecules given in high dose [23, 24]. This therapy inhibits survival signals and pathways that take part in the development of multi-drug resistance in cancer cells.
Oncogenes, mutated tumor supressor genes, survival and apoptotic genes, causing tumor initiation and progression, are major targets for RNAi-based therapy. Simultaneous suppression of one target gene or multiple genes has provided a significant advantage in cancer therapy. siRNAs can be designed for effective gene knockdown by targeting any gene or multiple genes in cells [25]. siRNAs are likely to be more effective than other antisense approaches because of many properties such as a highly specific mRNA degradation, cell-to-cell spreading of gene silencing effect, long silencing activity, improved stability
In clinical trials, the most of siRNAs have been given by local administration. When siRNAs are delivered to target tissue locally, lower siRNA doses can be used for pharmacologic effect (e.g., saline-based formulation, or excipiants such as 5% dextrose) and any drug delivery approaches (e.g., liposome, nanoparticle, and complexes) [28]. However, systemic drug administration by intravenous injection is required for cancer diseases [7]. In systemic effect, siRNAs must encounter several extra- and intra-cellular barriers until it reaches the target cell and tissue. siRNAs cannot freely cross physiological and cellular barriers because of their high molecular weight and negative charge. The significant challenges of using siRNA are their poor cellular uptake, degradation by serum nucleases, and rapid elimination. These factors and barriers reduce therapeutic effect of siRNA. Therefore, efficient
siRNAs have large molecular weight (~13 kDa) and are polyanionic nature (~40 negative phosphate charge) and are easily degraded by enzymes in cells, tissues, and bloodstream. In addition, siRNAs cannot easily cross the cell membrane [29]. The naked siRNAs are readily degraded by serum endonucleases. The half-life of circulating naked siRNA is less than 10 minutes because of its rapid clearance by the kidneys, so that they cannot reach to target cell efficiently. The gene silencing activity of unmodified or uncomplexed siRNAs is little or absent [31]. To solve this problem, two strategies are used: chemical modifications and conjugation of siRNA molecules or use of gene delivery systems for increasing efficiency of RNAi-based therapeutics.
Chemical modification is the major approach to overcome
Other chemical strategies for siRNA are cholesterol, folate, and aptamer conjugation and peptide modification. siRNAs can associate with aptamers, ligands, and antibodies by electrostatic interaction or direct conjugation. The conjugation of these functional groups provides cell- or tissue-specific targeting and efficient delivery. As a result, the efficacy of silencing can be increased [1].
Viral and non-viral vectors have been extensively used in the siRNA-based therapy. Viral vectors encoding shRNA have a high gene transduction and gene silencing effects. Adeno-associated viral vectors, lentiviral vectors, and adenoviral vectors have been extensively used in gene knockdown studies [35]. The transfering of shRNA-encoding vectors into the nucleus of cells have obtained high and long-term shRNA expression. In addition, viral vectors can integrate the host genome [14]. Although viral vectors have a high gene transfection efficiency, the challenges such as inflammatory reactions, strong immunogenicity, insertional mutagenesis, and oncogenic transformation of viral vectors can cause important safety concerns. In addition, some viral vectors have low capacity for transgene insertion. To overcome these problems, non-viral vectors have been developed and used in siRNA delivery. Compared to viral vectors, non-viral vectors have several advantages such as lack of immunogenicity, low or no integration into genome, large-scale production, and use of wide variety of nucleic acids size [36]. However, the transfection efficiency of non-viral vectors is not as high as the viral vectors.
The non-viral delivery of siRNA and shRNA therapeutics to target tumor cells is a multistep process. To achieve efficient delivery and therapeutic gene silencing, siRNAs should be stable in biological fluids and must have above mentioned properties [37, 38]. The circulating siRNAs after systemic administration must be evaded from the reticuloendothelial system (RES). Negatively charged siRNAs gain the positive charge after complexed with cationic charged polymers. This positive charge facilitates cellular internalization of siRNAs; however, the cationic charge increase non-specific interactions by non-target cells, negatively charged serum proteins, and extracellular matrix. As a consequence of these non-specific interactions, clot-like accumulations or aggregations are formed. Complexes are entrapped in the endothelial capillary bed or taken up by RES recognition. While RES organs such as spleen, liver, and bone marrow uptake the major part of injected dose, the minor part of this reaches to tumors [25, 37, 39].
Non-viral delivery vectors prolong the biological half-life and mean residence time of siRNA, and they enhance accumulation of siRNA molecules in tumor tissues. siRNA therapeutics can be accumulated into cancer tissue by enhanced permeability and retention (EPR) effect as a result of discontinuous vasculature (permeation) and poor lymphatic drainage (retention) in the abnormal tumor blood vessels compared to the normal blood vessels. Tumor endothelium allows penetration of macromolecules [37, 38].
The other challanges of RNAi-based therapeutics delivery to the tumor tissues after systemic circulation are crossing of cellular membrane, intracellular traffic into the cells with endosomal/lysosomal compartments, release of siRNA or shRNA from carriers, and nuclear transport for vector-based siRNA/shRNA therapeutics and entry to cytoplasm for siRNA-based therapeutics. The cell membrane is an important extracellular barrier for siRNA uptake. The average size of a single siRNA molecule is less than 10 nm. Despite their small size, polyanionic nature and hydrophilicity of siRNA make crossing of biological membranes difficult [18]. To overcome this problem, the complexation of negatively charged siRNA with cationic polymers or lipids are performed. The net positive charge of this formulations facilitates binding to negatively charged cell membranes, following internalization by adsorptive pinocytosis. For cell-type specific delivery, targeting ligands, antibodies, and aptamer-binding non-viral vectors pass through the cell membrane by receptor-mediated endocytosis [1]. After crossing from the cell membrane, siRNAs and vector-based siRNAs/shRNAs encounter several intracellular barriers that include the endosomal trafficking, unpackaging of siRNA, and nuclear traffic. The intracellular traffic of endosomal content is important for succesful siRNA delivery. When siRNA released from the carrier reaches cytosol, RNAi mechanism is induced inside the cells. However, for the onset of RNAi effect, transfer of vector-based siRNA/shRNA to the nucleus is required. In the delivery process, early release of siRNA from endosome is required. If siRNA remains inside the endosome for long time, it will be degraded. Therefore, different agents (fusogenic protein) conjugated with polymers disrupt the endosomal membrane. In addition, polymers possess proton-sponge effect (polyethyleneimine, PEI), which have been used to induce osmotic swelling and subsequent disruption of the endosome [15].
Negatively charged siRNAs or shRNAs can readily bind to cationic polymers or load to the nanocarriers by ionic interactions. Nanosized complexes or polyplexes by electrostatic interactions and nanoparticle formulations by encapsulation have been developed for efficient siRNA/shRNA delivery. Thus, siRNAs can be protected from nuclease attack and cellular uptake of siRNAs via endocytic pathway faciliated. Many natural and synthetic polymers are used for gene delivery, such as polyethyleneimine (PEI), poly-l-lysine (PLL), chitosan, protamine, gelatin, atelocollagen, cationic polypeptides, cyclodextran polymers, dendrimers, poly-lactide-co-glycolide (PLGA), and polydimethylaminoethylmethacrylate (PDMAEMA) [34]. In addition, polyethyleneglycol (PEG) is widely used as a linker between polymer and ligand or nucleic acid or for binding of siRNA onto nanocarrier surface [40].
Among the non-viral vectors, chitosan or its derivatives are attractive where chitosan has been shown to be biodegradable, biocompatible, non-toxic, mucoadhesive, and non-inflammatory and has low cost of production. Chitosan is a cationic polysaccharide, consisting of
Chitosan-based nanocarriers are prepared by three different methods. These include simple complexation, ionic gelation (siRNA entrapment), and adsorption of siRNA onto the surface of chitosan nanoparticles [42]. The molecular weight and degree of deacetylation of chitosan influence its solubility, hydrophobicity, charge density, and thus the interaction ability with nucleic acids. The N/P ratio (ratio between chitosan nitrogen per siRNA phosphate) of chitosan/siRNA nanoplexes is an important factor for optimization of complex properties (size and zeta potential), transfection, and gene silencing efficiency. Increasing the N/P ratio not only helps to obtain a high transfection efficiency but also enhances toxicity. The excess of free chitosan in the formulations can interact with cell membrane and cellular process, and thus, may reduce cell viability [41].
Chitosan has a great potential in siRNA-based cancer therapy studies, because it can be safely and efficiently delivered to cancer cells. It is reported that chitosan or modified chitosan nanoplexes and nanoparticles as delivery system exerted antitumoral effects in different cancers [43–48].
Howard et al. [43] developed chitosan nanoparticles using polyelectrolyte complexation method. The size of nanoparticles was between 40 and 600 nm. The endogenous enhanced green fluorescent protein (EGFP) silencing efficiency with nanoparticles was found to be 77.9 and 89.3% in human lung carcinoma cells (H1299) and murine peritoneal macrophages. The siRNA/chitosan nanoparticles reduced EGFP expression (43%) compared to untreated control in transgenic EGFP mice. They suggested that this chitosan-based system can be used in the treatment of systemic and mucosal diseases.
Salva and Akbuga [44] studied silencing effect of chitosan/
Salva et al. [46] also studied the IL-4 encoded plasmid (pIL-4) to improve the therapeutic efficacy of siRNA targeting
In another study, Salva et al. [47] obtained enhanced silencing effect by using siRNAs targeting to
Yang et al. [48] reported that chitosan/siRNA
Wang et al. [49] prepared the chitosan-TPP (tripolyphosphate) nanoparticles by ionic gelation method for the delivery of shRNA expressing vector to the human rhabdomyosarcoma (RD) cell line and for the inhibition of
Huang et al. [50] studied the effect of chitosan/shRNA
In order to increase the transfection efficiency of chitosan, different modifications are made on the structure of chitosan. Modified forms of chitosan such as carboxymethyl or trimethyl chitosan, trisaccharide-substituted chitosan oligomers, and succinated or galactosylated chitosan are formed. Chitosan is also conjugated with folic acid or PEG [51].
Jere et al. [52] used chitosan-graft-polyethylenimine (CHI-g-PEI) copolymer for delivery of shRNA
Noh et al. [53] prepared a copolymer containing additional cationic moieties linked with chitosan to enhance the cationic charge of chitosan. Therefore, chitosan derivation with poly-l-arginine (PLR) and polyethyleneglycol (PEG) (PLR-grafted CS) polyplexes were used for
Fernandes et al. [54] investigated folate conjugation to improve gene transfection efficiency of chitosan. When chitosan was conjugated with folate, the folate-chitosan-siRNA complexes have increased gene silencing efficiency because of promoted uptake in HeLa and OV-3 cell lines, which are known to have high folate receptor expression. Higher transfection efficiency and lower toxicity of folate-chitosan complexes are reported in folate receptor–positive cells.
Cell penetrating peptide-based systems may improve cellular uptake and gene silencing efficiency of siRNAs without side effects. Protamine is a cationic, non-toxic polypeptide that has membrane translocation and nuclear localization activities because of its arginine-rich amino acid sequences. In addition to its stabilization enhancing properties, protamine is known to exhibit cell penetrating activity and is an important compound for several cancer targeting systems [55].
Salva et al. [46] have developed ternary nanoplexes of chitosan/protamine/siRNA targeting
Erdem-Cakmak et al. [56] reported that addition of protamine to chitosan complexes increased the silencing of
Song et al. [57] used protamine/antibody fusion protein to deliver siRNAs targeting
Choi et al. [58] reported that complexes prepared with low molecular weight protamine (LMWP) inhibited cell growth by suppressing
Polyethylenimines (PEIs) are water-soluble cationic synthetic polymers. They can be synthesized in different lengths and different molecular weights such as branched (bPEI) or linear (lPEI) and low molecular weight (<1000 Da) or high molecular weight (>1000 kDa). PEI has a high cationic charge density because of the protonation of its primary, secondary, and tertiary amine groups positioned at every third nitrogen [59]. While in linear PEI all nitrogen atoms are protonable, in the branched form, two-thirds of nitrogens can be charged. PEI can lead to proton accumulation in endosome, which was brought in by endosomal ATPase with an influx of chloride anion. Proton accumulation in endolysosome counteracts pH decrease, inhibits nucleases and unbalances endosome osmolarity depend on CI concentration and results in osmotic swelling of endosome. This effect of PEI is named as “proton sponge effect”. PEI may enhance intracellular delivery by facilitating endosomal escape and induce lysosomal distruption, endosomal release, and DNA/siRNA protection from lysosomal degradation by buffering endosomes [60].
The molecular weight of PEI is important in the development of gene delivery and level of cytotoxicity in cells. The high molecular weight PEI has higher transfection efficiency than low molecular weight PEIs. PEI has a high electrostatic capacity, which can provide strong electrostatic interactions with the siRNA and contribute to cell membrane binding and internalization. Especially, the 25 kDa bPEI is one of the most effective non-viral vectors in gene silencing because of efficient endosomal escape. However, the high positive charge of bPEI leads to severe cytotoxicity and non-specific interactions with serum proteins [61, 62]. The cytotoxicity of PEIs can be decreased with modification of free amine groups or conjugation of cell binding and targeting ligands. Therefore, graft copolymers have been usually preferred as a delivery system.
Schiffelers et al. [63] prepared PEGylated PEI nanoplexes with Arg-Gly-Asp (RGD) peptide ligand containing siRNA targeting
Jiang et al. [64] studied anti-
Park et al. [61] synthesized siRNA/(PEI-SS)-b-HA complexes and, after characterization, applied to
Among cationic polymers, poly (l-Lysine) (PLL) is one of the mostly studied polymers used for nucleic acid delivery. It formed complexes with DNA smaller than 100 nm. Its complexes can target different cells after binding suitable ligands. PLL can be easily produced in large scale and is physiologically stable and biosafe [65]. PLL may protect siRNA from degradation effect of nucleases. However, PLL has some hurdless that impade its clinical application. PLL does not have the proton buffering ability to enhance lysosomal release of transported siRNA. It can be modified also by addition of ligands [66].
The ternary copolymer mPEG-b-PLL-g(ss-IPEI) was used for siRNA delivery to SKOV-3 ovarian cancer treatment. Nanocomplexes were administered to SKOV-3-implated Balb/c mice and tumor growth inhibition was observed [67].
Dendrimers are highly branched spherical and synthetic multifunctional macromolecules. The surface functional groups of dendrimers can be modified to enhance biocompatibility and decrease toxicity. Polycationic dendrimers such as poly(amidoamine) (PAMAM) and poly(propyleneimine) (PPI) dendrimers, because of the high density of positive charges on the surface, are highly attractive for delivery of negatively charged pDNA, antisense oligonucleotide (AsODN), and siRNAs. PAMAM dendrimers have primary amine groups on their surface and tertiary amine groups inside. Their amine groups are complexed with siRNAs. Thus, compact structure promote cellular uptake of siRNA and tertiary amine groups initiate the proton sponge effect to enhance endosomal release of siRNA [68, 69].
Waite et al. [70] conjugated cationic PAMAM dendrimers with RGD targeting peptides to enhance the delivery efficiency of siRNA to glioma cells. They suggested a promising strategy of RGD-conjugated dendrimers for siRNA delivery to solid tumors.
Liu et al. [71] investigated
Atelocollagen, which is produced from bovine type I collagen, has biomaterial properties such as high biocompatibility, biodegredability, and low immunogenicity. Atelocollagen forms a helix of three polypeptide chains and has positive charge, which enable its binding to nucleic acid molecules [72]. At low temperature, atelocollagen exists in liquid form (2–10°C), therefore, it can be easily mixed with nucleic acid solutions [72, 73]. Thus, atelocollagen can increase cellular uptake, nuclease resistance, and prolong release of nucleic acids. The size, charge, and sustained release of atelocollagen/siRNA complexes can be altered by ratio of siRNA to atelocollagen [74, 75].
Takei et al. [76] first studied anti-tumoral effect of atelocollagen complexes containing siRNA
Koyanagi et al. [77] reported that siRNA targeting vasohibin-2 (
PLGA has been widely used as gene delivery system because of its biodegredability, biocompatibility, and non-toxic properties. FDA has approved PLGA as a pharmaceutical excipient. PLGA nanoparticles enter the cells efficiently by specific and non-specific endocytosis. Nanoparticles can release the encapsulated drug slowly leading to sustained drug effect [25].
Murata et al. [78] investigated anti-tumor effect of long-term sustained release of PLGA microspheres encapsulating anti-
Su et al. [79] prepared PEI-coated PLGA nanoparticles loaded with paclitaxel and
Cationic lipids are used as carrier for siRNA delivery. Liposomes and lipoplexes, as lipid-based delivery systems, have been widely used in local and systemic siRNA or shRNA delivery. Liposomes are microscopic vesicles that consist of single or multiple lipid bilayer, form in a sphere with an aqueous core. Nucleic acids can either be entrapped in the aqueous core of liposomes or attached to the lipid surface for delivery. The advantages of liposomes as delivery system include a high gene transfection efficiency, enhanced stabilization, easy penetration into cell membranes, efficient
Neutral lipids lead to less cellular toxicity and do not induce immune responses without the down-regulation of gene expression. However, neutral liposomes have shown low transfection efficiency because of their lack of surface charges [17]. The commonly used cationic lipids for siRNA delivery include 1,2-dioleoyloxy-3-trimethylammonium propane (DOTAP) and 1,2-di-o-octadecenyl-2-trimethylammonium propane (DOTMA) have combined with neutral lipids such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). This combination can enhance transfection efficiency. Because neutral lipids facilitate fusion to the host cell’s membrane, cationic lipids can facilitate electrostatically complexation with siRNA to obtain more stable formulation and entry to cells more easily [18]. Liposomes are usually more stable than lipoplex in biological fluids [5].
Lipid-based siRNA delivery strategies have shown as promising in cancer therapy. Tumor-targeting approaches have been used to enhance antitumor efficacy of these delivery systems. Specific delivery to target cells can be achieved by conjugation of ligands or molecules such as transferin or PEG on the surface of liposomes [20]. The targeting and prolonged circulation half-life of liposomes allow for the enhanced permeability of tumor vasculature, increased delivery to tumor tissue, and reduced side effects [34, 82]. Cationic liposomes containing siRNA targeting tumor-associated genes have been used to inhibit tumor growth and proliferation, induce apoptosis, and enhance the radiosensitivity of tumor cells [83–85].
Cationic lipids can interact with negatively charged siRNA by ionic interactions. Thus, self-assembly formed lipoplexes protect siRNA from enzymatic degradation, enhance cellular uptake of siRNA by endocytosis, enhance the release of siRNA from endosomal/lysosomal entrapment, and thus, promote siRNA accumulation in the cytosol [16]. Commercially available cationic lipid formulations such as Lipofectin®, Lipofectamine® (Invitrogen), Dharmafect® (Dharmacon), RNAifect® (Qiagen), and TransIT TKO® (Mirus) have been studied as tranfection reagents for siRNA delivery
To overcome the drawbacks of lipoplexes and liposomes, different nanostructures such as neutral lipid-based nanoliposomes, stable nucleic acid lipid particles (SNALP), and solid lipid nanoparticles (SLN) have been developed as siRNA delivery system. SNALPs are composed of cationic, neutral, and fusogenic lipid mixture. SNALPs increase cellular uptake and endosomal release of siRNA [4]. PEG-conjugated SNALPs represent exciting lipid-based systemic RNAi. The PEG-lipid conjugate improves the retention time to >10 hours [87]. Recently, Tekmira Pharmaceuticals [88] has developed siRNA-based drugs that are encapsulated in the SNALPs for delivery of siRNAs to target tissue by intravenous injection. SNALP-encapsulated siRNA targeting
Tekedereli et al. [91] indicated that knockdown of
Landen et al. [92] studied neutral nanoliposomes incorporating siRNA targeting
Salva et al. [47] investigated the effect of co-delivery of siRNA
In conclusion, siRNA-based therapeutics are new and potential targets in cancer studies. In cancer, different mechanisms including angiogenesis, and cell growth were studied as target pathways. However, siRNAs have different hurdles in treatment because of their short biological life in blood, instability, and poor cellular internalization. In order to overcome these hurdles two solutions are present: one is modification of siRNA and the other is use of suitable siRNA delivery system. In cancer treatment, viral and non-viral delivery systems are evaluated as siRNA delivery. Although limited information is available related to
The ever-increasing population growth of the world has resulted in putting more and more pressure on a piece of arable land demanding higher and higher production. The world statistics shows reduction of per capita arable land from 0.23 ha in 2000 to 0.19 ha in 2015. While the per capita arable land in North America is still 0.55 ha, the numbers for South Asia and East Asia- Pacific are 0.12 ha and 0.11 ha respectively (5–6 times lower than that of North America) [1]. The shrinkage of arable land compels the farmers to go for over dose of fertiliser application which is a main source of many kind of pollutions and emission. Food sector contributes to around quarters (26%) of the global greenhouse gas (GHG) emission out of which solely crop production practices cause
Sub-region | Food and fibre | Biodiversity | Land degradation |
---|---|---|---|
Moderately resilient | Highly vulnerable | Moderately vulnerable | |
Highly vulnerable | Moderately vulnerable | Highly vulnerable | |
Moderately resilient | Highly vulnerable | Moderately vulnerable | |
Highly vulnerable | Highly vulnerable | Highly vulnerable | |
Highly vulnerable | Highly vulnerable | Highly vulnerable | |
Highly vulnerable | Highly vulnerable | Highly vulnerable |
Sectoral vulnerability in food, land and biodegradation in sub-continents of Asia.
According to IPCC (Intergovernmental Panel on Climate Change) 2014 [3] record, the scenario of GHG emission is very critical in Asia as Asian agriculture causes an average of 44% of global agricultural GHG emission (Table 2).
Carbon pool | Carbon changes | Rate of carbon increase in the atmosphere | |
---|---|---|---|
Fossil fuel use | Land Use | ||
750 Gt | + 5.5 Gt yr.−1 | +1.6 Gt yr.−1 | +3.3 Gt yr.−1 |
Carbon pool size and changes due to human activities [4].
The agricultural GHG emission contributors such as enteric fermentation and paddy rice cultivation are the major source of methane emission whereas the major sources of nitrous oxide emission are application of manures and fertilisers. The worldwide contribution of paddy rice cultivation towards GHG emission (CH4) is 11%. For higher crop production farmers rely on synthetic fertiliser application which is a rapidly growing source of emission having the increase rate of around 37% since 2001 [5]. Along with that the use of large number of machineries are the source of CO2 emission due to burning of fossil fuel. The imbalanced fertilisation is another reason for the release of soil carbon to the atmosphere (Figure 1).
Contribution of various agricultural sectors towards GHG emission in Asia. See [
To meet the daily food requirements, the agricultural stakeholders must make two kind of assessments in order to understand the impact of climate change on food and crop production i.e., mitigation and adaptation. Mitigation will reduce the emission of GHG from agricultural sources whereas adaptation will enable the agricultural sectors to perform well in the existing climate change situation through modified management and production systems. Both the approaches can be regulated through various policies e.g., ensuring the economic value of carbon and its sequestration will be an important development in the agriculture sector [7]. The adaptive-mitigation techniques to capture carbon in soil in organic form is a potential factor for controlling CO2 emission as well as a factor for improving soil quality and health.
Carbon storage in terrestrial system is important as soil can hold three times more carbon than vegetations that they support. The Soil carbon pool which is the largest reactive carbon in terrestrial ecosystem [8], is estimated to be 2500 Pg (1015) up to 1 mt depth, of which soil organic carbon is about 1500 Pg. This stock accounts for about 3.2 times the size of atmospheric carbon pool and 4 times that of biotic pool [6, 9]. Thus, capturing the carbon from agricultural lands in stable form can reduce CO2 content of the atmosphere.
Again, the global distribution of carbon and its storage potential is highly influenced by climatic conditions such as temperature and precipitation [10]. The higher decomposition rate controlled by higher oxidation of organic matter result in lower Soil Organic Carbon (SOC) in the tropics as compared to higher SOC of cooler regions. Though all the parts of Asian croplands contain moderate amount of carbon, and all together they account for about 25% of global cropland carbon [11]. But the regions of South Asia with low level of SOC and with serious degradation problems are global highest in carbon storage per hectare basis (0.62–1.28 t C/ha/yr) over 2.9 million km2 of land which all together turns out to be 2.2 to 4.5 Pg C storage/yr. in South Asia [11]. Thus, the management practices which are proved to be potential drivers of SOC enrichment must be encouraged as mitigative measure in agricultural soils.
Soil Organic carbon (SOC) is the controlling factor for soils physical, chemical, biological and ecological functionality and wellbeing. Not only soil’s health and productive capacity but soil carbon can also mitigate hazardous climate change. Quality and quantity of SOC; its dynamics/turnover is the main governing factor of soils ecosystem functions. A huge loss (50 to 75% and with magnitude of loss of around 30 to 60 Mg C/ha) of antecedent soil C pool has occurred due to land conversion, cultivation and erosion associated with it in most agricultural ecosystems [12]. Generally, agricultural soils contain considerably less SOC than soils under natural vegetation, hence, these lands are deprived of C than their ecological potential.
Carbon management practices (CMP) aim to sequester i.e., to capture and secure storage of carbon that would otherwise be emitted to, or remain, in the atmosphere. In other words, CMP is enhancing and/or maintaining soil carbon not allowing it to escape out to the atmosphere. In agricultural fields, addition of biomass carbon and organic manure is a direct approach but stabilisation of the soil carbon is through its physico-chemical property. Physical mechanism includes formation of organo-mineral complexes, encapsulation in microaggregates within macroaggregates, deeper placement of carbon in the soil profile away from natural and anthropogenic perturbation zone [12]. At the same time, the producer must seek for those practices which will promote sequestration of SOC in croplands without compromising the provision of ecosystem services such as food, fodder, fibre or other agricultural products. Thus, it is very crucial to understand the mechanism of carbon stabilisation by improving the mean residence time (MRT) and by offsetting anthropogenic emissions [13] which is vary according to the climatic condition and soil properties and also on existing soil carbon content of the particular region. For example, the same management practice which are proved to increase SOC can result in high amount of loss and unintended consequences in those soils which are already saturated with organic carbon [14] (Table 3).
Attributes | Mechanism |
---|---|
Physical stability | Depth distribution, Aggregate stabilisation, Organic macromolecules. |
Chemical recalcitrance | Charred materials, Interaction with cations, Hydrophobicity, Complexation with clay minerals, intermolecular interaction. |
Biotic mechanisms | Recalcitrant fractions, Structural composition, Condensation reaction. |
Mechanism of increasing MRT of SOC for its stabilisation.
A 4% increase in global agricultural soil carbon pool up to 1 m depth, 2–3 Gt C can be sequestered annually which would drawdown global anthropogenic GHG emission by 20–35% [15] but practicality has many constraints. For example, in countries with low (inherent) SOC like India, high rate of decomposition due to high temperature and the removal of crop residues does not allow this concept to work well [16]. Due to a greater surface area and charge density, organic matter can react with soil particles to form organo-mineral complexes. The mean residence time of carbon fractions are functions of their turnover rate which is dependent on the degree of protection within soil matrix [17]. Chemical protection involves formation of some recalcitrant compounds [18] like non- acid hydrolysable carbon fraction, aromatic compounds, double chained hydrocarbons and hydrophobic compounds which are not easily decomposed by microorganisms.
Change in soil carbon is a balance sheet of carbon input and output through mineralisation, loss, other emissions etc. [10]. So, the key for sequestering SOC is increasing carbon inputs and reducing carbon outputs. Cropping system biomass productivity has primary control over this carbon input through proper fertiliser, land, water management practices based on exiting soil and climatic condition. Integrated and balanced fertiliser application positively affect both above ground and below ground biomass and crop productivity. This adds more amount of organic matter to the soil directly in the form of straw returns, roots, exudates and organic manures directly. The organic carbon present in soil is very much prone to oxidation if neither biochemically protected (depends on its composition) not physically protected (in soil aggregates). So, researches focus on those practices which are helpful to protect pre-existing soil aggregates and/or to promote the genesis of new soil aggregates or to achieve both objectives of CMP.
Important carbon management practices are:
conservation agriculture (CA),
Cover crop
Crop rotation and diversification
Integrated and balanced nutrition (use of organic amendments viz. Crop residue, FYM, Compost, Biochar)
This is the technology of a set of management practices which aims at conserving the natural resources and biodiversity in the crop land and are characterised by the three principles e.g., i) No/minimum soil disturbance, ii) permanent organic cover or cover crops, and iii) crop diversification. Each principle individually and combinedly contribute towards carbon enrichment in soil. Build-up of carbon in soil can be successful through increased input, reduced decomposition and loss or both. Cultivation of previously uncultivated land can lead to 20%–40% loss in the native carbon in the initial years following initial cultivation [19]. Restoring that carbon in soil through addition and protection can be a potential carbon management practice. Every input like fertiliser, pesticide and irrigation has a carry a ‘hidden carbon cost, thus optimising their quantity in a crop management practice should be estimated in the carbon balance sheet [20]. Historically, excessive cultivation operations like tillage can expose SOC for decomposition by microbes which further may cause many land degradation problems such as erosion and soil structural decline. Enhanced soil disturbance triggers carbon losses from soil system via increased decomposition and erosion of SOM. All these ultimately adds to the atmosphere as CO2 fluxes or to the water resource [21]. Soil carbon levels of agricultural soils are lower than corresponding soils under natural vegetation or fallow that indicates the potential for soil carbon storage. In agricultural systems, soil carbon levels tend to be variable and dependent on management practices. Reducing soil disturbance can reduce rate of oxidation of organic matter and provide protection to the microbial habitat. Rate of decomposition can also be reduced by introducing slowly decomposing residues in the rotation. Intensifying crop rotation, legumes and green manure crops in crop cycle, elimination of fallow period, cover crop and residue mulch enhances soil carbon input in the form of both above ground and below ground biomass. The principles of conservation agriculture rotate around the concept of biomass addition and its protection through less soil disturbance. Soil C level and its composition under no-tillage and stubble retention (SOC = 2.5%) was more than the same soil under 3 pass tillage and stubble burning (SOC = 1.5%) after 19 years [4]. Reduced tillage increases the potential of soil c sequestration over conventional tillage practices as described in Figure 2. The concept of achieving steady state carbon status in cultivated soil through maximisation of organic input (residues, root biomass, organic amendments) is depicted in Figure 3. Conservation agriculture technology can be a potential method for conserving soil moisture, supplying plant nutrient and mitigate pathogen, peat and weed infestation there by cutting off fertiliser, pesticide requirement. Every input like fertiliser, pesticide and irrigation has a carry a ‘hidden carbon cost, thus optimising their quantity in a crop management practice should be estimated in the carbon balance sheet [23]. A study conducted by [20] Sapkota et al. (2015) in the Indo-Gangetic region showed that conventional rice- wheat cropping system has 27% higher GHG emission (in terms of CO2 equivalence) as compared to zero tilled rice- wheat crop rotation with residue mulching [23]. Sapkota et al. (2014) found the carbon dioxide efflux so also the global warming potential of wheat (through life cycle analysis) for its unit production under conventional tillage based practice is 10 times higher than no tillage based production. Introduction of legume in crop rotation and residue addition to the soil help reducing fertiliser requirement and energy need in arable systems. Considering the fact that, the annual global fertiliser leads to an annual release of 300 Tg of CO2 into the atmosphere during fertiliser manufacturing process [24], any management practice that will reduce the chemical fertiliser requirement with optimised output is highly environment friendly. They also explained that the release of every 2.6–3.7 kg CO2 per every 1 Kg of synthesised N, is produced from fossil fuel thus causing a net contribution to atmospheric amount of CO2 [24].
Changes in SOC content in cultivated soil as a result of tillage pattern over years [
Mechanism of achieving steady state SOC through input addition. Adopted from [
While the carbon sequestration in soil will occur at a certain point of time (until saturation) depending upon the soil type, reduction in emission owing to less energy requirement, fossil fuel consumption and machinery use will continue until the practice is carried out [25]. Zero tillage cuts the fuel consumption for land preparation so also CO2 emission. (Erenstein and Laxmi 2008) [26] found that adoption of ZT in wheat- maize system of the IGP could save an average of 36 L diesel ha–1 which is equivalent to a reduction in 93 kg CO2 emission ha−1 yr.−1 Sapkota et al. (2015) [20].
The carbon stock–enhancing effect of SOC management practice of conservation is possible due to reduced disturbance which is the prime factor in maintaining soils physical stability. This physical wellness of a soil system has positive effect on microbial habitat, their activities and the natural ecosystem functions of soil like nutrient cycling, buffering capacity, cation exchange etc.
The first principle is no tillage which is growing crops in soil without causing soil disturbance except for sowing or reduced tillage that is significant reduction of soil disturbance through less frequent passes of tillage, tillage in specific portion of the field which is in form of strip or ridge and shallower depth of tillage. Second principle aims at keeping a permanent organic cover on the soil surface in the form of residue mulch, growing cover crops both of which addresses many aspects of soil protection in the form of hindrance towards water, wind erosion, improved soil aggregation, enrichment of substate for microbial growth and functionality and many other chemical properties such as nitrogen fixation, carbon sequestration, etc. the third principle i.e. crop diversification is an essential tool for promoting better soil health as it has a role in allowing nutrient uptake of differently rooted crops from different depths, promoting microbial diversity, reducing disease and pest infestation there by allowing a better plant growth and biomass addition.
Soil particles are bound together by temporary (i.e., fungal hyphae and roots) and transient binding agents (i.e., microbial- and plant-derived polysaccharides through organic matter decomposition) [27]. In presence of these agents, aggregation is promoted and with time the microbially restructured carbohydrate molecules get attached with finer soil particles like clay and silt which is a stable form as compared to particulate organic matter (POM). With elimination of soil disturbance (tillage), soil organic matter gets strongly bound to clay particles in the form of macroaggregates and microaggregates within the macroaggregates. Again, microaggregates within the macroaggregates constitute a secure habitat soil microorganism, soil disturbance destroys the microbial habitat, affects its activity. In non-disturbed soil, the particulate organic matter present in macroaggregates get to be predominantly stabilised within microaggregates owing to the slow turnover rate [28]. On the other hand, a higher turnover of POM is seen due to tillage because they get exposed to rapid microbial attack preventing its incorporation into microaggregates as fine POM. In short, tillage leads to carbon loss through breakdown of C-rich macroaggregates and a decrease in microaggregate formation. Research has shown that 90% of total difference in SOC in soils of varying type and climate is due to the microaggregate-associated C fraction [29]. Thus, a slower turnover of this fraction in zero tillage allows greater protection and stabilisation of coarse POM over time through mineral-bound C decomposition product formation in the microaggregates-within-macroaggregates promoting long-term soil C sequestration in agricultural soils. The process of aggregate formation and protection under no tillage system is shown in the right flowchart whereas, disruption due to tillage is described in the left (Figure 4), The bold lines are implicative of higher amount.
Aggregate formation in a no-tillage as well as conventional tillage system. Adopted from [
Not only microbial habitat, but also macrofauna population is promoted under no tillage practices in absence of physical abrasion and habitat destruction as happens under conventional tillage practices.
Availability of protected habitat and higher C- input directly influence microbial population in a positive way. Generally, in tillage induced environment there is dominance of
Mechanism operated in soils under CA practice for enhancing C-pool size.
The main social issue with farmers of IGP are, less time interval between harvesting of kharif crop and sowing of succeeding crop, fodder requirement of domestic animals, use of crop residue as a source of energy for domestic purpose. Mostly farmers adopt the simple way of residue management i.e., residue burning which is undoubtfully a huge source of CO2. In that case, may the carbon addition be very small due to residue return to the field that would otherwise have been emitted to the atmosphere, is a sure shot CO2 efflux mitigation principle (Powlson et al., 2016) [34] (Figure 6, Table 4).
Macro and micro aggregate formation in soil through binding agents. Adopted from [
The intercrops or catch crops can be grown in field instead of keeping the land fallow before sowing of the next fallow crop. A
Monoculture is a technique that favour strong outbreak of diseases and pests. Again, due to same root architecture in every season, plants access nutrient from a specific depth. These affect plant growth and production. On the other hand, the stratified root architecture associated with crop diversification allows plants to uptake nutrients from various depths of the soil. Rhizosphere provides suitable environment for microbial diversity and proliferation in different level of the soil. Crop diversification has been shown to reduce the emergence and damage of such pests and diseases. This promotes better above ground as well as below ground biomass production in crop plant by which crop diversification directly contributes to carbon enrichment in soil. Crop rotation or mixed cultivar use instead of single genotype are found to improve resilience towards climate change extremities, pest, disease occurrence, enhance yield stability and reduce fertiliser footprint which ultimately cuts contribution of crop production towards CO2 emission. A study conducted by Hu et al. (2016) [42] showed that there is 46% less soil respiration and 10% less emission in wheat- maize intercropping as compared to maize monoculture in north-west China. In case of intensive cropping systems, minimum one legume crop is necessary for soil carbon stabilisation along with other soil quality benefits. Legume plants are characterised by deeper root system, high leaf shedding, higher root exudates accelerate rhizospheric activity [43]. The quality and quantity of both root exudates and microbial polysaccharides (rich in lignopolyphenol complexes) promote macro and meso aggregate associated carbon storage in “rotation with legume” system than “cereal- cereal” system which is a good indicator of carbon sequestration [44, 45]. A life cycle-assessment (LCA) review conducted by Clune et al. (2017) [46] from 2000 to 2015 around the world highlighted that pulses have a very low Global Warming Potential (GWP) values (0.50–0.51 kg CO2 eq kg−1 which makes inclusion of a pulse crop in crop rotation, a win-win situation.
Pulse cultivation has other beneficial effect on soil environment viz.; pulses during summer can conserve moisture because soil covering through litterfall protects soil surface from atmospheric temperature. Not only the exudate or biomass quality but the management practices associated with crop rotation (irrigation, fertiliser dose, nitrogen fixation, amount of residue recycled for different crop rotations) cause variation on biomass input into a system. Legume crops acquire their N from biological nitrogen fixation (except for starter dose of nitrogen fertiliser) rather than from the soil as nitrate a slight decrease in pH of soil occurs. The reduction in soil pH in neutral and alkaline soil environments promote microbial activity in root zone and increase the nutrient availability [45]. Therefore, pulse in rotation enhances the macroaggregates rather than cereal- cereal system. Though the results of legume in rotation are strong for higher carbon management, a cereal- cereal rotation improve the passive carbon pool because higher carbon: nitrogen ratio of such crop residues [45]. Cereal in a rotation has also found to be important in environmental aspect as per a study conducted by Senbayram et al. (2016) [47] who found that monocropped faba beans lead to three times higher cumulative N2O emissions than that of unfertilized wheat whereas faba bean wheat intercropping could lower the cumulative N2O emissions by 31% as compared to N-fertilised wheat.
Proliferated root condition under diversified cropping system supports a hierarchy of aggregate formation (macroaggregates followed by microaggregates within macroaggregates). Plant roots are residues bind the individual soil particles together to form macroaggregates then fine root hairs grow into these aggregates. The organic acids, enzymes, and other C-rich compounds exuded by these roots support higher microbial populations and act as the nucleation centre for microaggregate formation [48, 49]. The microbially altered organic compounds get polymerised and are then strongly bound to finer particles (silt & clay) inside of the macroaggregates. These newly formed occluded microaggregates are C and N enriched [48, 49].
With increase in demand of food per capita per unit land area, farmers are adopting higher fertiliser application in hope of getting higher yield. But in contrast the expectation, over use of chemical fertiliser result in severe soil degradation which is a major contributor towards soil carbon loss and higher GHG emission. As a correction measure to such issue, many scient have looked for the role of integrated (chemical+ organic) and balanced fertilisation on GHG emission reduction and soil carbon enrichment. As per a study conducted in subtropical north-western states of India, application of organics along with chemical fertilisers reduces the gaseous N losses as compared to fertiliser nitrogen alone in rice-wheat system [50]. Addition of organics no doubt acted as the primary source of denitrification, but the carbon balance was still positive. The higher yielding cropping systems created a scenario of higher CO2-C consumed by crops for photosynthesis than the total flux of CO2-C from rice-wheat system even with the use of organics thus making it a sink of atmospheric CO2-C [50].
Integrated nutrient management (INM) technology improves the physical, chemical and biological activity of the soil, which leads to a healthy plant population and higher yield. Organic treatments like FYM, sulphitation press mud (SPM), green gram residue (GR) and rice-wheat crop residues (CR) may consistently increase biomass yields and increase C inputs in soil. The strong influence from increasing C stock through long-term balanced fertilisation under rice–wheat cropping system was found by Nayak et al., 2012 [51]. Organic material incorporation improved soil aggregation and structural stability and resulted in higher C content in macroaggregates, thereby improved C sequestration potential in soils. However, the C accumulation in aggregates may determine by the kind and source of organic inputs. Thus, study by Das
Organic amendment like FYM, vermicompost, biochar etc. have higher humification rate constant but less decomposition rate thus, improve the amount and stability of SOC through their addition. An incubation study by Naher et al., 2020 [54] described that carbon mineralisation rate was 0.011 tonne year−1 for INM followed by balanced fertiliser and control which in turn enhance the scope for SOC sequestration in soil for sustainable rice production.
A study conducted by Bharali et al. (2018) [55] in the north-eastern India showed that addition of organics (Azolla compost or green manure) along with chemical fertilisers resulted in higher emission worth of higher global warming potential however, the carbon efficiency ratio and amount of fixed carbon in terms of grain yield was found to be higher and lower in case of Azolla compost as compared to chemical fertiliser alone. Likewise, in case of NPK + green manure, there is 64% higher emission over the control, a lower carbon efficiency ratio but higher total C fixed in a form of grain carbon (Table 5). Though INM is not a direct solution for reducing C efflux, the extra organics added may result in more emission as compared to sole chemical fertiliser addition, it also contributes to sufficiently higher C fixation in the form of grain C which ultimately shows to have a positive carbon balance due to INM.
Treatments | Carbon efficiency ratio | Global warming potential (kg CO2 ha−1) | % increase in yield over control | % increase in emission over control |
---|---|---|---|---|
NPK | 13.82 ± 0.82 | 540.60 ± 21.25 | — | — |
NPK + Green manure | 9.94 ± 0.24 | 887.40 ± 12.11 | 10.70 | 64.15 |
NPK+ Azolla compost | 16.90 ± 0.25 | 625.20 ± 13.03 | 27.43 | 15.66 |
LSD (T) | 0.634 | 21.068 |
Effect of INM on emission and yield.
A review done by Wu and Ma (2015) [56] shows the effect on INM on different soil properties and crop growth in countries of Asia is summarised in Table 6.
Soil attributes | Soil functions |
---|---|
Soil physical properties | Organic amendments support aggregate formation, aeration, higher water holding capacity |
Nutrition supply | Release of nutrient over a long period of time, improved use efficiency, higher SOC, more aggregate SOC, reduce phosphate fixation, reduced the mining of K from the soil |
Soil reactions | Increase CEC, buffering, rhizospheric elemental transformation |
Soil biological property | Microbial species diversity, soil enzymes, microbial biomass C (MBC), slow establishment and persistence of pathogens |
Agronomic properties | Better root establishment, higher grain, straw production |
Effect of INM on various soil properties for better soil health and crop production.
A meta-analysis conducted by Waqas et al. (2020) [57] all over China to study the effect of balanced, imbalanced, integrated, sole fertilisation and their combinations on yield sustainability (YSI), yield variability index (YVI) suggest that balanced and integrated fertilisation has highest YSI and lowest YVI and balanced chemical fertilisation has less YVI as compared to sole organics addition or imbalanced chemical fertilisation. The result supports the fact that integrated and balanced fertilisation supports carbon addition through higher above ground and below ground biomass production. Even imbalanced+ organic fertilisation and organic fertilisation alone can increase SOC due to direct addition of stabilised carbon through organic amendments. Organic amendments are also supply additional nutrients (N, P, S, etc.) into the soil which are responsible for production of fine fraction of soil organic matter [58]. The direct and indirect carbon input through integrated fertiliser management is a great adoptive measure as carbon management practice. In general, cold temperature promotes carbon sequestration due to low rate of organic matter decomposition but in higher temperature region with higher productivity and consequently increased biomass carbon input into soil [59], SOC can be improved through stable aggregate formation.
Sole and continuous use of chemical fertilisers inhibit the micro-organisms and their biochemical compositions, which reduced the aggregate formation. But the fresh organic matter added through organic amendments supply promote microbial polysaccharide formation (water soluble and hydrolysable substrate) that also promote aggregate formation. In completely no fertiliser condition, higher root extraction causes shattering of macroaggregates and breaking up soil structure [60].
Biochar as an organic amendment is also a great choice because the carbon-rich material has many organic functional groups to which act as bridge to form strong complexes with soil and is also helpful to increase soil aggregation through charged surface, porous structure and high cation exchange capacity [61].
Biochar amendments has two mechanisms of improving SOC dynamics (1) promoting soil aggregation thereby physical protection of bound SOC (2) Negative priming by means of higher recalcitrant organic substrate pool having low decomposition rate [62] (Tables 7 and 8).
Treatment | Carbon mineralisation rate (t yr−1) | Carbon stock (t ha−1 year−1) | Carbon sequestration (kg ha−1 year−1) |
---|---|---|---|
Fertiliser control | 0.009 | 10.95 | −213 |
Balanced fertiliser | 0.010 | 17.30 | −72.15 |
INM | 0.011 | 26.30 | 127.86 |
Carbon sequestration in soil with rice–rice–fallow cropping sequence for 10 years [54].
Country | Control | NPK | INM | Reference |
---|---|---|---|---|
New Delhi, India | 7.53 | 8.50 | [63] | |
Kanpur, India | 3.73 | 4.59 | [45] | |
Bangladesh | 9.8 | 13.3 | [64] | |
China | 13.81 | 13.40 (Only N) | [65] |
Total organic carbon (TOC) content under INM and chemical fertilisation practice in various regions of Asia (TOC given in g/kg).
Bold letters are to make the values distinctly visible from treatment details only.
In the degraded land Soil organic carbon acts as the centre of soil health through positive regulation of soil physical, chemical, biological and ecological functions. The integrated management practice like conservation agriculture does not only add carbon to the soil directly but also reduce fossil fuel CO2 emission, oxidation of SOC. Cover crops and crop diversity are beneficial for combating disease- pest occurrence, support healthy above ground and below ground biomass production. Legume in a crop rotation supports aggregate formation and stabilisation and ultimately protects the aggregate associated carbon through chemical polymerisation and physical occlusion. INM is beneficial over imbalanced chemical or sole chemical fertiliser application. Though biochar is another effective amendment for carbon sequestration in agricultural land, the higher carbon foot print associated with its production technique (CO2 production during pyrolysis and more CO2 emission from amended plots) can offset it as a climate change mitigative- adoptive practice. Soil C sequestration is not a permanent solution for all climate change related issues but is a holistic approach to restore degraded soil, reduce erosion, increase agronomic yields and reduce CO2 emission into the atmosphere at the same time. Thus, careful selection of carbon management practice according to climatic and soil condition is necessary for making it agriculturally and environment friendly.
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Concrete",slug:"fly-ash-as-a-cementitious-material-for-concrete",totalDownloads:849,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"This paper presents a review on fly ash as prime materials used for geopolymer. Due to its advantages of abundant resources, less in cost, great workability and high physical properties, fly ash leads to achieving high mechanical properties. Fly ash is considered as one of the largest generated industrial solid wastes or so-called industrial by-products, around the world particularly in China, India, and USA. The characteristics of fly ash allow it to be a geotechnical material to produce geopolymer cement or concrete as an alternative of ordinary Portland cement. Many efforts are made in this direction to formulate a suitable mix design of fly ash-based geopolymer by focusing on fly ash as the main prime material. The physical properties, chemical compositions, and chemical activation of fly ash are analyzed and evaluated in this review paper. Reference has been made to different ASTM, ACI standards, and other researches work in geopolymer area.",book:{id:"9916",slug:"zero-energy-buildings-new-approaches-and-technologies",title:"Zero-Energy Buildings",fullTitle:"Zero-Energy Buildings - New Approaches and Technologies"},signatures:"Aissa Bouaissi, Long Yuan Li, Mohd Mustafa Al Bakri Abdullah, Romisuhani Ahmad, Rafiza Abdul Razak and Zarina Yahya",authors:null},{id:"73729",doi:"10.5772/intechopen.93500",title:"Solar Energy and Its Purpose in Net-Zero Energy Building",slug:"solar-energy-and-its-purpose-in-net-zero-energy-building",totalDownloads:614,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"The Net Zero Energy Building is generally described as an extremely energy-efficient building in which the residual electricity demand is provided by renewable energy. Solar power is also regarded to be the most readily available and usable form of renewable electricity produced at the building site. In contrast, energy conservation is viewed as an influential national for achieving a building’s net zero energy status. This chapter aims to show the value of the synergy between energy conservation and solar energy transfer to NZEBs at the global and regional levels. To achieve these goals, both energy demand building and the potential supply of solar energy in buildings have been forecasted in various regions, climatic conditions, and types of buildings. Building energy consumption was evaluated based on a bottom-up energy model developed by 3CSEP and data inputs from the Bottom-Up Energy Analysis System (BUENAS) model under two scenarios of differing degrees of energy efficiency intention. The study results indicate that the acquisition of sustainable energy consumption is critical for solar-powered net zero energy buildings in various building styles and environments. The chapter calls for the value of government measures that incorporate energy conservation and renewable energy.",book:{id:"9916",slug:"zero-energy-buildings-new-approaches-and-technologies",title:"Zero-Energy Buildings",fullTitle:"Zero-Energy Buildings - New Approaches and Technologies"},signatures:"Mostafa Esmaeili Shayan",authors:[{id:"317852",title:"Ph.D.",name:"Mostafa",middleName:null,surname:"Esmaeili Shayan",slug:"mostafa-esmaeili-shayan",fullName:"Mostafa Esmaeili Shayan"}]},{id:"67105",doi:"10.5772/intechopen.86279",title:"Social Innovation and Environmental Sustainability in Social Housing Policies: Learning from Two Experimental Case Studies in Italy",slug:"social-innovation-and-environmental-sustainability-in-social-housing-policies-learning-from-two-expe",totalDownloads:1026,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"This chapter critically examines approaches and solutions developed by social housing to sustainably respond to the housing emergency plaguing contemporary cities and Italian cities in particular. In a broader perspective, we also investigate how housing has become ‘difficult’ in Europe and the poorest segments of the population run the risk of having their right to housing dramatically denied. Analysing housing in terms of its procedural dimension, we focus on two Italian case studies that evoke a new way of inhabiting the city, cases in which high standards characterised social housing and yet remain accessible to all. The Sharing hotel residence in Turin and Zoia social housing in Milan combine housing with other socially innovative measures in a framework of sustainability and avant-garde construction. These are significant examples that speak to issues such as temporariness, flexibility and the coordination of measures. These two cases both pursued objectives having to do with social, planning, architectural and environmental quality, albeit each in their own way. There are by now numerous examples of social housing in Europe and these have recently attracted growing interest in Italy as well; in this country, however, such projects represent valid instances of experimentation but are not at all widespread.",book:{id:"7650",slug:"different-strategies-of-housing-design",title:"Different Strategies of Housing Design",fullTitle:"Different Strategies of Housing Design"},signatures:"Rossana Galdini and Silvia Lucciarini",authors:[{id:"281246",title:"Dr.",name:"Silvia",middleName:null,surname:"Lucciarini",slug:"silvia-lucciarini",fullName:"Silvia Lucciarini"},{id:"282958",title:"Prof.",name:"Rossana",middleName:null,surname:"Galdini",slug:"rossana-galdini",fullName:"Rossana Galdini"}]},{id:"57401",doi:"10.5772/intechopen.71325",title:"Basic Schemes: Preparations for Applying Control Science to Sustainable Design",slug:"basic-schemes-preparations-for-applying-control-science-to-sustainable-design",totalDownloads:1254,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"It is the ultimate goal for humankind to deal with various problems and achieve sustainability. Control science can be applied to all goal-oriented tasks and has already produced remarkable results. Accordingly, applying control science to the task of achieving sustainability is a rational and reliable approach. In order to apply control science to sustainability issues, our first study has shown the “basic control system for sustainability” as well as the “model of sustainability.” After that, in order to identify system components of practical control systems for promoting sustainable design, we have devised “two-step preparatory work for sustainable design.” The two steps of this preparatory work are “determining the relationships between the standard human activities and sustainability” and “sustainability checkup on human activities as an object.”",book:{id:"5692",slug:"sustainable-home-design-by-applying-control-science",title:"Sustainable Home Design by Applying Control Science",fullTitle:"Sustainable Home Design by Applying Control Science"},signatures:"Kazutoshi Fujihira",authors:[{id:"69662",title:"BSc.",name:"Kazutoshi",middleName:null,surname:"Fujihira",slug:"kazutoshi-fujihira",fullName:"Kazutoshi Fujihira"}]},{id:"72850",doi:"10.5772/intechopen.92725",title:"Computational Analysis of a Lecture Room Ventilation System",slug:"computational-analysis-of-a-lecture-room-ventilation-system",totalDownloads:868,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"The level of Indoor Air Quality (IAQ) has become a big topic of research, and improving it using passive ventilation methods is imperative due to the cost saving potentials. Designing lecture buildings to use less energy or Zero Energy (ZE) has become more important, and analysing buildings before construction can save money in design changes. This research analyses the performance (thermal comfort [TC]) of a lecture room, investigate the use of passive ventilation methods and determine the energy-saving potential of the proposed passive ventilation method using Computational Fluid Dynamics (CFD). Results obtained showed that air change per hour at a wind velocity of 0.05 m/s was 3.10, which was below standards. Therefore, the lecture hall needs external passive ventilation systems (Solar Chimney [SC]) for improved indoor air quality at minimum cost. Also, it was observed that the proposed passive ventilation (SC) system with the size between 1 and 100 m3, made an improvement upon the natural ventilation in the room. There was a 66.69% increase after 10 years in the saving of energy and cost using Solar Chimney as compared to Fans, which depicts that truly energy and cost were saved using passive ventilation systems rather than mechanical ventilation systems.",book:{id:"9916",slug:"zero-energy-buildings-new-approaches-and-technologies",title:"Zero-Energy Buildings",fullTitle:"Zero-Energy Buildings - New Approaches and Technologies"},signatures:"Abayomi Layeni, Collins Nwaokocha, Olalekan Olamide, Solomon Giwa, Samuel Tongo, Olawale Onabanjo, Taiwo Samuel, Olabode Olanipekun, Oluwasegun Alabi, Kasali Adedeji, Olusegun Samuel, Jagun Zaid Oluwadurotimi, Olaolu Folorunsho, Jacob Adebayo and Folashade Oniyide",authors:null}],mostDownloadedChaptersLast30Days:[{id:"71982",title:"Net-Zero Energy Buildings: Principles and Applications",slug:"net-zero-energy-buildings-principles-and-applications",totalDownloads:2288,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Global warming and climate change are rising issues during the last couple of decades. With residential and commercial buildings being the largest energy consumers, sources are being depleted at a much faster pace in the recent decades. Recent statistics shows that 14% of humans are active participant to protect the environment with an additional 48% sympathetic but not active. In this chapter, net-zero energy buildings design tools and applications are presented that can help designers in the commercial and residential sectors design their buildings to be net-zero energy buildings. Case studies with benefits and challenges will be presented to illustrate the different designs to achieve a net-zero energy building (NZEB).",book:{id:"9916",slug:"zero-energy-buildings-new-approaches-and-technologies",title:"Zero-Energy Buildings",fullTitle:"Zero-Energy Buildings - New Approaches and Technologies"},signatures:"Maher Shehadi",authors:null},{id:"57400",title:"Case Study: Detached House Designed by Following the Control System",slug:"case-study-detached-house-designed-by-following-the-control-system",totalDownloads:1578,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"The previous chapter has demonstrated the control system for promoting sustainable housing design in which the sustainable design guidelines and sustainability checklist are incorporated. Following this control system, we have actually designed and constructed a detached house. To be concrete, the homeowner and the architects of the housing manufacture have designed the home’s parts, or elements, so that as much as possible the elements’ variables meet their desired values. The sustainable design guidelines and sustainability checklist have been readily accepted because the material and spatial elements are equivalent to real parts of the home. After the home started to be used, we have obtained external evaluations of the home’s sustainability performance. For example, CASBEE for Detached Houses, a comprehensive assessment system, has readily ranked the house in the highest “S.” An energy-saving performance assessment has shown that this home has reduced energy consumption by over 70%, as compared with the average home. On the other hand, the reactions of the occupants and visitors have indicated the comfort, healthiness and safety of this house. Furthermore, this home has received a sustainable housing award, especially due to its extremely high sustainability and energy-saving performance.",book:{id:"5692",slug:"sustainable-home-design-by-applying-control-science",title:"Sustainable Home Design by Applying Control Science",fullTitle:"Sustainable Home Design by Applying Control Science"},signatures:"Kazutoshi Fujihira",authors:[{id:"69662",title:"BSc.",name:"Kazutoshi",middleName:null,surname:"Fujihira",slug:"kazutoshi-fujihira",fullName:"Kazutoshi Fujihira"}]},{id:"67084",title:"Comprehensive Strategy for Sustainable Housing Design",slug:"comprehensive-strategy-for-sustainable-housing-design",totalDownloads:1385,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Sustainable housing needs to be designed to maximize occupants’ well-being and minimize the environmental load. The pursuit of combining these two different aspects toward sustainability is a goal-oriented task. The science of control can be applied to all goal-oriented tasks. Therefore, applying control science, we have been progressing in research on sustainable housing design. Our previous study has produced the control system for promoting sustainable housing design in which sustainable design guidelines and sustainability checklist are incorporated. Based on these accomplished results, this study has comprehensively visualized the process of producing and revising the sustainable design guidelines and sustainability checklist. Following this visualized process, also this study has concretely shown the production and revision processes of the sustainable design guidelines. The study results suggest that the comprehensive visualization can make these processes more manageable and help system designers to produce and revise the guidelines more efficiently. Furthermore, these results have led to indicating how to adjust the guidelines to different countries or regions as well as changing situations over time.",book:{id:"7650",slug:"different-strategies-of-housing-design",title:"Different Strategies of Housing Design",fullTitle:"Different Strategies of Housing Design"},signatures:"Kazutoshi Fujihira",authors:[{id:"69662",title:"BSc.",name:"Kazutoshi",middleName:null,surname:"Fujihira",slug:"kazutoshi-fujihira",fullName:"Kazutoshi Fujihira"}]},{id:"65804",title:"Effects of Street Geometry on Airflow Regimes for Natural Ventilation in Three Different Street Configurations in Enugu City",slug:"effects-of-street-geometry-on-airflow-regimes-for-natural-ventilation-in-three-different-street-conf",totalDownloads:1420,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Efficient natural ventilation is dependent on the micro climate conditions of an urban environment. This is affected by ambient wind flow, radiation and air temperatures. The airflow within the urban street can be cultivated into two regions. The first is a recirculation region, which forms in the near wake of each building. The Second is a ventilated region downstream of the recirculation region, formed when the street is sufficiently wide. The development of the flow into these two regions depends on geometry. This chapter looks at the impacts of street geometry on these regions of airflow cultivation in three different street configurations in high density residential settlements in Enugu city. It utilized schematic analysis of airflow regimes to identify the behaviors of flow in these street configurations relative to the height and width ratios of the street canyon. This schematic analysis can be utilized in preliminary design studies by city and building designers for justifying street dimensions and configurations in tropical regions where natural ventilation is paramount.",book:{id:"7650",slug:"different-strategies-of-housing-design",title:"Different Strategies of Housing Design",fullTitle:"Different Strategies of Housing Design"},signatures:"Jideofor Anselm Akubue",authors:[{id:"139659",title:"Dr.",name:"Akubue",middleName:"Jideofor",surname:"Anselm",slug:"akubue-anselm",fullName:"Akubue Anselm"}]},{id:"66000",title:"Fundamentals of Natural Ventilation Design within Dwellings",slug:"fundamentals-of-natural-ventilation-design-within-dwellings",totalDownloads:982,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Along with acoustical and lighting comfort, indoor air quality (IAQ) and thermal comfort upon households are essential to maintain a proper indoor environment, therefore ensuring a welfare toward the occupants. Nevertheless, sometimes, these features are neglected by building designers and constructers, causing problems such as the so-called sick building syndrome (SBS) and thermal discomfort, among others. Although there are short-term solutions such as purifiers, extractors, fans, and air conditioning, eventually these methods become not sustainable activities that consume energy and emit polluting gases such as chlorofluorocarbons. One alternative to this is natural ventilation, understood as the airflow throughout a building caused by changes of pressures naturally produced. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. 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Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:{name:"Kobe College",institutionURL:null,country:{name:"Japan"}}}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. 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Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"17",type:"subseries",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11413,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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