\r\n\t
",isbn:"978-1-83968-760-0",printIsbn:"978-1-83968-759-4",pdfIsbn:"978-1-83968-761-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"cc49d6034d85f8f2e2890c6acc3cc629",bookSignature:"Dr. Abhijit Biswas",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10285.jpg",keywords:"Mott Insulators, Semi Metals, Polycrystals, Single Crystals, Electronic Properties, Magnetic Properties, PLD, MBE, Topological Insulators, Topological Hall Effect, Devices Applications, Catalysis",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 9th 2020",dateEndSecondStepPublish:"October 7th 2020",dateEndThirdStepPublish:"December 6th 2020",dateEndFourthStepPublish:"February 24th 2021",dateEndFifthStepPublish:"April 25th 2021",remainingDaysToSecondStep:"5 months",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"A pioneering researcher in the field of tailoring metal oxide crystal surfaces and growth as well as engineering of thin films for various emergent phenomena and energy applications. Dr. Biswas received his Ph.D. from POSTECH, South Korea.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"194151",title:"Dr.",name:"Abhijit",middleName:null,surname:"Biswas",slug:"abhijit-biswas",fullName:"Abhijit Biswas",profilePictureURL:"https://mts.intechopen.com/storage/users/194151/images/system/194151.png",biography:"Dr. Abhijit Biswas is a research associate at the Indian Institute of Science Education and Research (IISER) Pune, in India. His research goal is to design and synthesize highest quality epitaxial heterostructures and superlattices, to play with their internal degrees of freedom to exploit the structure–property relationships, in order to find the next-generation multi-functional materials, in view of applications and of fundamental interest. His current research interest ranges from growth of novel perovskite oxides to non-oxides epitaxial films, down to its ultra-thin limit, to observe unforeseeable phenomena. He is also engaged in the growth of high quality epitaxial layered carbides and two-dimensional non-oxide thin films, to exploit the strain, dimension, and quantum confinement effect. His recent work also includes the metal-insulator transitions and magneto-transport phenomena in strong spin-orbit coupled epitaxial perovskite oxide thin films by reducing dimensionality as well as strain engineering. He is also extremely interested in the various energy related environment friendly future technological applications of thin films. In his early research career, he had also extensively worked on the tailoring of metal oxide crystal surfaces to obtain the atomic flatness with single terminating layer. Currently, he is also serving as a reviewer of several reputed peer-review journals.\nDr. Biswas received his B.Sc. in Physics from Kalyani University, followed by M.Sc in Physics (specialization in experimental condensed matter physics) from Indian Institute of Technology (IIT), Bombay. His Ph.D., also in experimental condensed matter physics, was awarded by POSTECH, South Korea for his work on the transport phenomena in perovskite oxide thin films. Before moving back to India as a national post-doctoral fellow, he was a post-doc at POSTECH working in the field of growth and characterizations of strong spin-orbit coupled metal oxide thin films.",institutionString:"Indian Institute of Science Education and Research Pune",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Indian Institute of Science Education and Research Pune",institutionURL:null,country:{name:"India"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"20",title:"Physics",slug:"physics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"205697",firstName:"Kristina",lastName:"Kardum Cvitan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/205697/images/5186_n.jpg",email:"kristina.k@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"8356",title:"Metastable, Spintronics Materials and Mechanics of Deformable Bodies",subtitle:"Recent Progress",isOpenForSubmission:!1,hash:"1550f1986ce9bcc0db87d407a8b47078",slug:"solid-state-physics-metastable-spintronics-materials-and-mechanics-of-deformable-bodies-recent-progress",bookSignature:"Subbarayan Sivasankaran, Pramoda Kumar Nayak and Ezgi Günay",coverURL:"https://cdn.intechopen.com/books/images_new/8356.jpg",editedByType:"Edited by",editors:[{id:"190989",title:"Dr.",name:"Subbarayan",surname:"Sivasankaran",slug:"subbarayan-sivasankaran",fullName:"Subbarayan Sivasankaran"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"47335",title:"Cell Sheet Engineering for Periodontal Regeneration",doi:"10.5772/58901",slug:"cell-sheet-engineering-for-periodontal-regeneration",body:'Periodontitis is a world-wide infectious disease that destroys the tooth-supporting attachment apparatus, which consists of alveolar bone, cementum, and periodontal ligament. Recent studies have reported numerous associations between periodontitis and systemic diseases, such as cardiovascular disease (de Oliveira et al., 2010) and diabetes mellitus (Lalla and Papapanou, 2011), as well as a higher risk of preterm low birth-weight babies (Offenbacher et al., 1996). Furthermore, researches have recently shown that Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) is also associated with severe periodontitis (Vescovi et al., 2011). Therefore, periodontal treatment may not only contribute to oral hygiene but also improvement of systemic conditions (Seymour et al., 2007). Conventional treatments, such as scaling, root-planing, and surgical cleaning, have been performed to remove the bacteria and contaminated tissue. However, these procedures frequently result in the formation of a weak attachment, a condition termed “long junctional epithelium (LJE)” (Caton et al., 1980), wherein the patients tend to present with a recurrence of disease without maintenance therapies (Axelsson and Lindhe, 1981). To overcome this problem, various regenerative therapies, such as guided tissue regeneration (GTR) and enamel matrix derivative, have been introduced in clinical practice. The use of cell-occlusive membranes for GTR is regarded as the first generation of periodontal regeneration, whereas the development and use of growth factors and endogenous regenerative technology for periodontal regeneration is regarded as the second generation of periodontal regeneration (Ishikawa et al., 2009). However, the outcomes of these studies were limited and associated with poor clinical predictability (Esposito et al., 2009). Therefore, stem cell-based approaches for periodontal regeneration have been studied and translated into clinical settings as the third generation. In this chapter, we would like to describe the principles of “Cell Sheet Engineering” and its application of clinical settings, featuring our recent translational research for periodontal regeneration.
The cell delivery for periodontal regeneration is usually performed with the combination use of cells and scaffolds, although the location and the differentiation of transplanted is difficult to control. In contrast to approaches that utilize scaffolds, we have developed an alternative technology for cell transplantation using temperature responsive culture dishes, which we call “Cell Sheet Engineering”.
Poly(N-isopropylacrylamide) (PIPAAm) is a temperature responsive polymer that has been widely utilized for novel biomedical applications. We have developed a PIPAAm-grafted surface as a smart biointerface wherein cell attachment/detachment can be easily controlled by simply changing the temperature (Okano et al., 1995; Yamada et al., 1990). This surface is slightly hydrophobic under cell culture conditions of 37 °C, but readily becomes hydrated and hydrophilic below its lower critical solution temperature (LCST) of 32 °C. Cells can adhere, spread, and proliferate similarly to that on ungrafted tissue culture grade polystyrene surfaces at 37 °C (Figure 1A), and cells detach from the surface by reducing temperature below LCST, making it possible to harvest the cells from the culture surfaces without the use of proteolytic enzymes (Figure 1B).
The principle of “Cell Sheet Engineering”.
A: Cells can attach and proliferate on grafted surface of the temperature responsive polymer (poly (N-isopropylacrylamide: PIPAAm) at 37 °C, wherein PIPAAm is extensively dehydrated and compact. B: At temperatures below 32 °C, cells with extracellular matrix proteins spontaneously detach from the temperature responsive culture dishes, wherein PIPAAm is fully hydrated with an extended-chain conformation. A simple temperature change can control cell attachment/detachment without any damages. Modified and reprint from Iwata et al., 2013.
The application of this technology has enabled the retrieval of confluently cultured cells, such as keratinocytes (Yamato et al., 2001), corneal epithelial cell sheets (Nishida et al., 2004a), and oral mucosal epithelial cells (Ohki et al., 2006) in the form of a “cell sheet”. The epithelial cell sheets are multi-layered and preserve the integrity of proteins such as E-cadherin and laminin 5 that are typically destroyed in the process of enzymatic treatments (Yamato et al., 2001). In addition, recent studies revealed that epithelial cell sheets can be fabricated using temperature responsive culture inserts without feeder layers (Murakami et al., 2006a; b), thereby eliminating exclude xenogeneic factors for animal-free cell transplantation (Takagi et al., 2011).
To fabricate thick tissues, cell sheets can be stacked in layers because they can connect to one another very quickly. A study demonstrated that bilayer cardiomyocyte sheets were completely coupled 46 ± 3 min (mean ± SEM) after the initial layering (Haraguchi et al., 2006), suggesting that multi-layered cell sheets can communicate and become synchronized as functional tissues. Based on this study, multi-layered transplantation was performed (Shimizu et al., 2006b). When more than three cardiomyocyte sheets were layered and transplanted into the subcutaneous space in rats, the appearance of fibrosis and disordered vasculature indicated the presence of fibrotic areas within the transplanted laminar structures. Although the rapid establishment of microvascular networks occurred within the engineered tissues, this formation of new vessels did not rescue the tissues when the thickness was above 80 µm. Using a multiple-step transplantation protocol at 1 or 2 day intervals resulted in rapid neovascularization of the engineered myocardial tissues with a thickness of more than 1 mm (Shimizu et al., 2006b), and these results led us to fabricate prevascularized cell sheets (Sekine et al., 2011). Recent studies demonstrate that the combination of different types of cells, for example an endothelial cell sheet sandwiched with other types of cell sheets, can lead to pre-vascularization in vitro, which may allow the graft to survive and function (Haraguchi et al., 2012; Pirraco et al., 2011). Furthermore, the three-dimensional manipulation of fibroblast cell sheets and micro-patterned endothelial cells with a gelatin-coated stacking manipulator produced microvascular-like networks within a 5-day in vitro culture (Tsuda et al., 2007). Non-patterned endothelial cell sheets and other types of cell sheets with a fibrin gel manipulator can also produce pre-vascular networks both in vitro (Asakawa et al., 2010) and in vivo (Sasagawa et al., 2009).
From the beginning of the 21st century, various types of cells have been extracted, cultured in temperature responsive dishes, and fabricated as cell sheets. Transplantation has been performed, and the efficacy of these cell sheets was evaluated in most of the studies.
Limbal stem-cell deficiency by ocular trauma or diseases causes corneal opacification and loss of vision. To recruit limbal stem cells, a novel cell-sheet manipulation technology that takes advantage of temperature responsive culture surfaces was developed (Nishida et al., 2004a). The results reveal that multi-layered corneal epithelial cell sheets were successfully fabricated and that their characteristics were similar to those of native tissues. Transplantation of these cell sheets induced corneal surface reconstruction in rabbits. For patients who suffer from unilateral limbal stem deficiency, corneal epithelial cell sheets can be cultured from autologous limbal stem cells. When the objective is to repair the bilateral corneal stem cell deficiency, autologous oral mucosal epithelial cells are utilized to create oral mucosal epithelial cell sheets. The cell sheets contain both cell-to-cell junctions and extracellular matrix proteins, and can be transplanted without the use of any carrier substrates or sutures. Therefore, oral mucosal epithelial sheets were examined as an alternative cell source to expand the possibilities of autologous transplantation. Autologous transplantation to rabbit corneal surfaces successfully reconstructed the corneal surface and restored transparency. Four weeks after the transplantation, epithelial stratification was similar to that of normal corneal epithelia, although the keratin expression profile retained characteristics of the oral mucosal epithelium.
To enhance the function of cardiac tissue, neonatal rat cardiomyocyte sheets were fabricated and examined (Shimizu et al., 2002). When 4 sheets were layered, spontaneous beating of the engineered constructs was observed. When they were transplanted subcutaneously, heart tissue-like structures and neovascularization within the contractile tissues were observed. The long-term survival of pulsatile cardiac grafts was confirmed for more than one year in rats (Shimizu et al., 2006a). Another study was performed to create thick tissue in rats (Shimizu et al., 2006b). However, the thickness limit for the layered cell sheets of subcutaneous tissue was ~80 μm (3 layers). To overcome this limitation, several transplantations of triple-layer grafts were performed, resulting in an approximately 1 mm-thick myocardium with a well-organized microvascular network. Other types of cell sheets were also examined to improve cardiac function. Adipose-derived mesenchymal stem cells in mice (Miyahara et al., 2006) and skeletal myoblasts in dogs, rats, and hamsters (Hata et al., 2006; Hoashi et al., 2009; Kondoh et al., 2006) were transplanted as cell sheets, demonstrating the efficacy of the method for cardiac repair.
Chondrocyte sheets applicable to cartilage regeneration were prepared using cell sheet manufacturing technique that takes advantage of temperature responsive culture dishes. The layered chondrocyte sheets were able to maintain the phenotype of cartilage and could be attached to sites that exhibited cartilage damage. The cell sheets act as a barrier for preventing the loss of proteoglycan from these sites and for protection against catabolic factors in the joints of rabbits (Kaneshiro et al., 2006).
With the recent development of endoscopic submucosal dissection (ESD), large esophageal cancers can be removed using a single procedure. However, complications, such as postoperative inflammation and stenosis, frequently occur after an aggressive ESD procedure, which can considerably affect the quality of life of the patient. Therefore, a novel treatment combining ESD and the endoscopic transplantation of tissue-engineered cell sheets created using autologous oral mucosal epithelial cells, was examined in a canine model (Ohki et al., 2006). The results confirm the efficacy of the novel combination of the endoscopic approach with the potential treatment of esophageal cancers that can effectively enhance wound healing and possibly prevent postoperative esophageal stenosis.
To address the demand for therapeutic benefits for patients suffering from liver disease, the development of new therapeutic applications is crucial. Therefore, hepatic tissue sheets transplanted into the subcutaneous space of mice have been investigated, resulting in the efficient engraftment of the surrounding cells, as well as the formation of a two-dimensional hepatic tissues network, which was stable for more than 200 days (Ohashi et al., 2007). The engineered hepatic cell sheets also showed several characteristics of liver-specific functionality, and the use of bilayered sheets enhanced these characteristics.
In thoracic surgery, the development of postoperative air leaks is the most common cause of prolonged hospitalization. To seal the lung leakage, use of autologous fibroblast sheets on the defects was demonstrated to be an effective treatment for permanently sealing air leaks in a dynamic fashion in rats (Kanzaki et al., 2007). Using roughly the same procedures, pleural defects were also closed by fibroblast sheets in pigs (Kanzaki et al., 2008).
Post-operative adhesions often cause severe complications such as bowel obstruction and abdominopelvic pain. The use of mesothelial cell sheets was investigated to prevent post-operative adhesions in a canine model (Asano et al., 2006). Mesothelial cells were harvested from tunica vaginalis (Asano et al., 2005) and cell sheets were fabricated on a fibrin gel. The results demonstrated that mesothelial cell sheets are effective for preventing post-operative adhesion formation.
The retinal pigment epithelium (RPE) plays an important role in maintaining the health of the neural retina. RPE cell sheets were fabricated as a monolayer structure with intact cell-to-cell junctions, similar to that of native RPE (Kubota et al., 2006). In the transplantation study, RPE cell sheets attached to the host tissues in the subretinal space were more effective than the use of injected isolated cell suspensions in rabbits (Yaji et al., 2009).
Augmentation cystoplasty using gastrointestinal flaps may induce severe complications such as lithiasis, urinary tract infection, and electrolyte imbalance. The use of viable, contiguous urothelial cell sheets cultured in vitro should eliminate these complications. Canine urothelial cell sheets were grown and their structures were shown to be appropriate (Shiroyanagi et al., 2003). Urothelial cell sheets were autografted onto dog demucosalized gastric flaps successfully, with no suturing or fixation, and generated a multi-layered urothelium in vivo (Shiroyanagi et al., 2004). The novel intact cell-sheet grafting method rapidly produced native-like epithelium in vivo.
To establish a novel approach for diabetes mellitus, pancreatic islet cell sheets were fabricated and transplanted in rats (Shimizu et al., 2009). Laminin-5 was coated on temperature responsive dishes to enhance the initial cell attachment, and the presence of specific molecules, such as insulin and glucagon, was also observed in the recipient site.
For hormonal deficiencies caused by endocrine organ diseases, continuous oral hormone administration is indispensable to supplement the shortage of hormones. To verify the cytotherapeutic approach, cells from rat thyroid were spread on temperature responsive culture dishes, and cell sheets were created (Arauchi et al., 2009). Rats were exposed to total thyroidectomy as hypothyroidism models and received the thyroid cell sheet transplantation 1 week after the total thyroidectomy. The transplantation of the thyroid cell sheets was able to restore the thyroid function 1 week after the cell sheet transplantation and the improvement was observed long after the surgery.
In Japan, 6 clinical trials using cell sheet engineering technology have been started or have already been completed.
The first clinical trial of the cell sheet engineering technology involved a corneal reconstruction using autologous mucosal epithelial cells, and the results were published in 2004 (Nishida et al., 2004b). Oral mucosal tissue was harvested from 4 patients with bilateral total corneal stem-cell deficiencies. Subsequently, cells were cultured for two weeks using a mitomycin C-treated 3T3 feeder layer and transplanted directly into the denuded corneal surfaces without sutures. The results demonstrated that complete re-epithelialization of the corneal surfaces occurred, and the vision of all patients was restored. Recently, autologous oral mucosal epithelial cell sheets cultured with UpCell-Insert technology (CellSeed, Tokyo, Japan) without the feeder layer were transplanted into 25 patients for the treatment of corneal limbal epithelial deficiency in France The safety of the products was established during the 360-day follow-up, and the results confirmed its efficacy for reconstructing the ocular surface. (Burillon et al., 2012).
Using a canine model (Ohki et al., 2006), autologous oral mucosal epithelial cell sheets were fabricated using the UpCell-Insert technology. After performing the esophageal endoscopic submucosal dissection to remove superficial esophageal neoplasms, cell sheets were transplanted, resulting in the complete prevention of stricture formation in patients with partial circumferential resection (Ohki et al., 2009; Ohki et al., 2012).
Autologous myoblast cells from a patient’s thigh were fabricated as cell sheets, and these cell sheets were transplanted into end-stage dilated cardiomyopathy patients in need of left ventricular assist systems (Sawa et al., 2012). The myoblastic cell sheets were transplanted into the affected part of the heart in the patients. The first patient was successfully treated and discharged from the hospital without requiring a ventricular assisting device.
A clinical trial for cartilage regeneration began in 2011 at Tokai University, Japan. In this study, autologous chondrocytes and synoviocytes were co-cultured with the UpCell-Insert technology. After a period of cultivation, co-cultured cell sheets were combined into three layers and transplanted into the cartilage defects of patients.
A clinical trial for preventing hearing loss began in 2014 at The Jikei University, Japan. Autologous nasal mucosa epithelial cell sheets were transplanted to the surface of bone of the middle ear, and inhibit such as the hyperplasy of granulation tissue and bone, and the progression of fibroblast within middle ear cavity, which induce hearing loss after the surgery of otitis media.
Our laboratory started to introduce cell sheet engineering for periodontal regeneration since sometime after 2000. A key event in periodontal regeneration involves the formation of periodontal ligament and cementum complex (MacNeil and Somerman, 1999), which is a thin surface structure that anchors the tooth to the alveolar socket. Several studies have demonstrated that the cell sheet engineering approach can deliver functional cells in the form of a thin layered sheet, wherein the extracellular matrices, cell-cell junctions, and cell-matrix interactions are well-preserved (Kumashiro et al., 2010). Thus, we have attempted to regenerate this periodontal attachment apparatus based on the technology of “cell sheet engineering” (Yang et al., 2007).
Human PDL (hPDL) cell sheets were successfully created using temperature responsive dishes, and the characteristics of hPDL cell sheets were investigated (Hasegawa et al., 2005). In this study, explant culture methods were utilized for the primary culture of hPDL cells. The hPDL cell sheets cultured with ascorbic acid were recovered from the culture dishes as a contiguous sheet accompanied by abundant extracellular matrix components, including type I collagen, integrin β1 and fibronectin. Then, hPDL cell sheets were transplanted as cell pellets into a mesial dehiscence model in athymic rats. Four weeks after surgery, newly formed immature fibers with obliquely anchored dentin surfaces were observed in all the experimental sites, whereas no such findings were observed in any control sites (Figure 2).These results suggest that this procedure based upon the principles of cell sheet engineering can be applied to periodontal regeneration.
PDL regeneration at 4 weeks postsurgery.
A: Nontransplanted control site. B: hPDL transplanted experimental site. Regeneration of periodontal ligament-like structure was observed only in the experimental site. Azan staining. Modified and reprint from Hasegawa et al., 2005.
Next, the optimal culture condition was examined. Because the osteoinductive medium, which contains 50 µg/ml of ascorbic acid, 10 mM β-glycerophosphate, and 10 nM dexamethasone, enhanced both osteoblastic/cementoblastic and the periodontal differentiation of PDL cells in vitro, we compared hPDL cell sheets cultured in the absence and presence of these osteoinductive supplements in a xenogeneic transplantation model (Flores et al., 2008a). Three layered hPDL cell sheets were constructed with fibrin gel and transplanted with a human dentin block into the back of a subcutaneous athymic rat. The constructs were excised for histological investigation 6 weeks after the transplantation. The three-layered hPDL cell sheets-dentin block constructs induced a new cementum-like hard tissue on the surface of the dentin in more than 60% of the samples. Collagen fibers were inserted perpendicularly into the newly formed cementum-like tissue, and this orientation resembled the native Sharpey’s fibers. In addition, the regenerative potential of hPDL cell sheets cultured with the osteoinductive medium the was confirmed, when hPDL cell sheets were transplanted onto the root surface of periodontal defects in athymic rat mandibles (Flores et al., 2008b). The results indicate that most of the specimens in the experimental group exhibited a newly-formed cementum and a new attachment of collagen fibers to the cementum layer. No clear cementum layer was observed in the control group (in the absence of osteoinductive supplements). As shown in these experiments, hPDL cells cultured with osteoinductive medium could contribute to the simultaneous regeneration of cementum and PDL.
Based on the successful results from small animal studies, we next utilized canine periodontal defect models. Dog PDL (dPDL) cells were extracted using collagenase/dispase digestion. Four individual dPDL cells were successfully isolated and expanded ex vivo. Cells were cultured in a standard medium with osteoinductive supplements for 5 days, because longer cultivation induced spontaneous detachment of cell sheets from the UpCell Surfaces. Three-layered dPDL cell sheets were fabiricated with woven polyglycolic acid (PGA) for cell sheet transfer. This PGA product has a number of advantages, including: 1) cell sheets can be easily peeled from temperature responsive dishes, because cell sheets can be attached to the fibers of the woven PGA, 2) the shrinkage of cell sheets can be prevented, 3) easy stacking of multi-layered cell sheets can be achived in a short period of time (see the video attached to the manuscript (Iwata et al., 2009)), 4) easy adjustment of different sizes of cell sheets can be used to cover any defect shape by simply trimming the cell sheets, 5) the ability to make contact on hard tissues and curved surfaces, and 6) the transplant is visible to the operators. dPDL cell sheets were transplanted into the surface of dental roots containing three-wall periodontal defects in an autologous manner, and bone defects were filled with porous beta-tricalcium phosphate (β-TCP). Cell sheet transplantation regenerated both new bone and cementum connecting with the well-oriented collagen fibers, while only limited bone regeneration was observed in the control group where cell sheet transplantation was not performed. These results suggest that PDL cells have multiple differentiation properties that allow for the regeneration of periodontal tissues composed of hard and soft tissues.
Next, we evaluated the safety and efficacy of PDL cell sheets in a one-wall infrabony defect model (Tsumanuma et al., 2011), which is considered to be a severe defect model (Kim et al., 2004). In this study, we also compared the differences in the periodontal healing of various cell sources. PDL cells, bone marrow derived mesenchymal stem cells, and alveolar periosteal cells were obtained from each animal, three-layered canine cell sheets were transplanted in an autologous manner, and bone defects were filled with porous β-TCP with 3% type I collagen gelto stabilize the graft shape. Eight weeks after transplantation, significantly more periodontal regeneration was observed in the newly formed cementum and well-oriented PDL fibers more in the PDL cell sheets group than in the other groups. These results indicate that PDL cell sheets combined with β-TCP/collagen scaffold serve as a promising tool for periodontal regeneration.
To protect human rights as subjects in clinical trials, the protocol of cytotherapy should be designed based on Good Clinical Practice (GCP) and Good Manufacturing Practice (GMP). Culturing hPDL cells from a single tooth is essential in performing our clinical trial. However, appropriate method for the extraction and expansion of hPDL cells are still not well understood. Thus, we determined the optimal method of isolation and expansion of hPDL cells and then examined their gene expression levels and differentiation potentials, and eventually validated the common characteristics of hPDL cells from 41 samples (Iwata et al., 2010). The hPDL cells were successfully extracted with collagenase/dispase, and then clonal proliferation was performed. Typically, 10 to 100 colonies were observed for a few days after the initial spreading. hPDL cells exhibit the ability to be highly proliferative when cultured at a low cell density. The cells were subcultured for 3 to 4 days, reaching one million cells in 2 weeks. Then, cells were spread on temperature responsive dishes to create a cell sheet in the presence of the osteoinductive medium. Cell sheets were harvested 2 weeks after spreading because the mRNA expression of osteogenic marker genes was strong after that period of time. Quality assurance tests were performed on at least 7 samples, and then the standard phenotypes of hPDL cell sheets were determined.
According to the GCP and GMP guidelines, hPDL cell sheets were created from three healthy volunteer donors at the GMP-grade Cell Processing Center (CPC) in our university (Washio et al., 2010). GMP-grade reagents and certified materials were used for culturing the hPDL cells. The safety and efficacy of “the product (hPDL cell sheets in this case)” was validated for a clinical trials. Prior to performing the cell culture, autologous serum was prepared from the donors. The hPDL cells were cultured under xeno-free conditions, and cell sheets were fabricated using the temperature responsive dishes. Culture sterility was confirmed using conventional tests. Safety was evaluated using the following tests: 1) the soft-agar colony-formation assay, 2) transplantation into nude mice, and 3) the karyotype test (Yoshida et al., 2012). The efficacy of the cell sheets was verified by transplantation with a dentin block into SCID mice. All of these tests revealed that hPDL cell sheets created at the CPC were safe and exhibited the ability to regenerate periodontal tissues. Another set of three hPDL cell sheets from healthy volunteer donors were created at the CPC to optimize the procedures.
After approval on the 5th of January 2011, our clinical trial called “Periodontal regeneration with autologous periodontal ligament cell sheets” was initiated to treat patients presenting with the following ailments: 1) infrabony defects with a probing depth of more than 4 mm after the initial therapy, 2) radiographic evidence of infrabony defects, and 3) a redundant tooth that contains healthy periodontal tissue as a cell source. All patients provided written informed consent according to the GCP. Exclusion criteria included the following: 1) relevant medical conditions contraindicating surgical interventions (e.g., diabetes mellitus, cardiovascular, kidney, liver, or lung disease, or compromised immune system), 2) pregnancy or lactation, and 3) heavy tobacco smoking (more than 11 cigarettes a day). The primary outcome of this trial is to evaluate the safety and efficacy of autologous transplantation of periodontal ligament cell sheets. As of the end of May in 2014, 10 cases of autologous PDL cell sheets were transplanted, and the healing process took place uneventfully.
The applications of cell sheet engineering for regenerative medicine are mentioned. Various types of cells have been examined and most of them improved the functions of recipients, suggesting that cell sheet engineering can be an alternative strategy for the therapy of tissue engineering. The implementation of robotic systems that allow the safe mass production of sterile cell sheets automatically, as well as further collaboration between researchers and medical professionals will make “cell sheet engineering” the leading edge solution for regenerative medicine (Elloumi-Hannachi et al., 2010).
This study was supported by Creation of innovation centers for advanced interdisciplinary research areas Program in the Project for Developing Innovation Systems “Cell Sheet Tissue Engineering Center (CSTEC)” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. Teruo Okano is a director of the board of Cell Seed, a stake holder of Cell Seed, and an inventor of cell sheet-related patent. Masayuki Yamato had been a science consultant of Cell Seed until 2011, stake holder and an inventor of cell sheet-related patent. Tokyo Women\'s Medical University is receiving research fund from CellSeed Inc.
Thrombosis is the leading cause of death in the world. Indeed, atherothrombosis including coronary artery diseases and cerebrovascular diseases is the top cause of death in various regions of the world [1]. Venous thrombosis including deep venous thrombosis and pulmonary embolism is the third cause of death in hospitalized patients [2]. Thrombosis is a disease caused by thrombi formed at various vessels. The major symptom differs substantially depending upon the site where the thrombi developed. Typically, arterial thrombosis such as myocardial infarction and ischemic stroke is symptomatic even when the thrombi are small (e.g., less than 1 mm in diameter) [3]. On the other hand, venous thrombosis is asymptomatic until thrombi become substantially large such as the ones that occlude several pulmonary arteries to cause pulmonary embolism [4]. In both arterial and venous thromboses, platelets are cells that contribute to initial thrombus formation. Coagulation and fibrinolysis are systems necessary to regulate the size of fibrin thrombi.
It is noteworthy that there is homogeneity in risk factors for various arterial/venous thromboses despite wide variation of clinical manifestation [5]. Framingham study demonstrated that cigarette smoking, diabetes mellitus (DM), dyslipidemia, and hypertension are strong predictors for the future onset of arterial thrombosis represented by acute myocardial infarction [6]. Recent international registries also confirm that these risk factors are contributing factors for the recurrence of cardiovascular events [7]. Moreover, international registries also suggested these parameters as risk factors of venous thrombosis [8]. These clinical observations suggested the presence of common pathways for the onset of arterial and venous thrombosis [9].
The Framingham registry suggested the contributory role of obesity and less exercise as the predictors for future prevalence of risk factors. These abnormalities represented as visceral obesity-related syndrome is named as “metabolic syndrome.” In metabolic syndrome patients, insulin resistance is one of the major contributors [10]. Increased body weight, high blood pressure, and dyslipidemia are common manifestations of metabolic syndrome. Long-term exposure to a high-calorie diet and lack of good exercise are supposed as underlining mechanisms for the onset of metabolic syndromes. The risk of thrombotic disease including arterial and venous thrombosis is speculated to be high in patients with metabolic syndrome.
Blood is flowing to maintain homeostasis inside the human body. Blood cells have specific functions: erythrocytes bring oxygen to tissues, leukocytes protect from infection, and platelets stop bleeding promptly. As shown in Figure 1, large and heavy erythrocytes tend to be located in the center of blood flow. Small cells of platelets circulate interacting with endothelial cells [11]. In the case where endothelial cells have a physiological function, platelets do not interact with them [12]. Platelets collide with the vessel wall and promptly go back to the blood flow without platelet activation. On the other hand, when endothelial cell function was disturbed by physical or chemical stimuli, endothelial cells lose their ability to keep antithrombotic function. Then, platelets immediately start the interaction with endothelial cells [12]. At the time, von Willebrand factor (VWF) is expressed on the cell surface of stimulated endothelial cells. Platelets capture VWF through glycoprotein (GP)Ibα. GPIbα is expressed on the surface of platelet regardless if they are activated or not [13]. Thus, initial adhesion of platelets at the site of endothelial cell damage occurs predominantly as a physical phenomenon, which occurs immediately without time-consuming biological process. Historically, the vast majority of vessel damage is caused by trauma. Rapid accumulation of platelets at the site of endothelial injury plays an important role to keep our blood in our vessel system for surviving.
Role of erythrocytes and blood flow in platelet adhesion at the site of endothelial injury. This figure demonstrates the three-dimensional distribution of erythrocytes, platelets, and endothelial cells. Erythrocytes accumulate in the center of blood flow by biorheological effects. Accordingly, platelets circulate close to endothelial cells. In the presence of normally functioning endothelial cells, platelets do not adhere nor are activated, but just return to blood flow (panel A). If the endothelial cell function was disturbed by various stimulations, platelets are adhered and activated through their interaction with von Willebrand factor (VWF).
The potential impact of erythrocytes for the onset and growth of thrombosis has first caught the interest of researchers in the 1960s [14]. Biorheological axial accumulation of flowing platelets was also recognized at the same time [15]. Clinical studies also support the notion that higher hematocrit values are related to higher risk of thrombotic diseases such as myocardial infarction [16]. These results strongly suggest the biophysical role of erythrocytes for thrombus formation. These rheological effects could hardly be controlled by food intake. In another aspect, erythrocytes also influence the function of platelet with biochemical modulation [17, 18, 19]. Indeed, erythrocytes are a huge source of ADP [20], which is one of the most potent platelet-stimulating agents [21, 22]. There is potential effects of food intake for influencing erythrocytes components which can influence thrombogenicity of platelet [23, 24].
Recent advances in computer technology allowed us to predict the structure and function of VWF bound with GPIbα from the physical movement of atoms and water molecules [25, 26]. By the method, physical force generated by VWF binding with GPIbα could be predicted. Platelet adhesion at injured vessel wall is summarized in Figure 2. Platelets are cells with a diameter of approximately 5 μm. But, when platelet adhered at the site of vessel damage, only part of platelet bound with VWF. Molecular dynamic prediction revealed that single bond of VWF and GPIbα could generate binding force approximately 70 pN [25]. Fluid dynamic force applied to platelets reaches to a couple hundred pN when the cell receives detaching force from arterial blood flow. Theoretically, several bonds between VWF and GPIbα are enough to stop platelets from adhering to the vessel wall. The mechanism of thrombus formation is a complicated process, but platelet adhesion under blood flow condition could now be constructed from physical movement of atoms and water molecules.
Platelet adhesion at the site of endothelial damage under blood flow conditions. Platelet adhesion is mediated exclusively by its glycoprotein (GP)Ibα binding with von Willebrand factor (VWF). Adhered platelets receive fluid dynamic force, but platelets continue to adhere until the detaching force becomes larger than the binding force generated between VWF and GPIbα.
It is of particular importance that endothelial damage is not caused only by acute physical or chemical stimulation. In the recent era, human beings enjoy longer life than those who lived hundreds of years ago. Just like carrying human being, vessel system become old when people become old. Longer time exposure of vessel wall to atherogenic lipids such as LDL cholesterol and its related local biological reaction causes atherosclerosis [27, 28]. Antithrombotic potential of endothelial cell in patients with atherosclerosis is reduced when compared to younger normal ones. Moreover, plaque rupture exposes subendothelial thrombotic materials to vessel lumen. Thus, atherothrombotic events occur frequently [29] in the era of aging society. The initial event resulting in symptomatic atherothrombosis is always platelet adhesion at the site of endothelial injury.
By understanding the mechanism of atherosclerosis and atherothrombosis, it is rather easy to understand that various types of food intake influence the risk of thrombosis. As regards nutritional factor, there is a hot discussion concerning cholesterol. Some suggested potential benefit of cholesterol restriction for prevention of atherothrombosis. The other suggest there are no relationship between daily cholesterol intake and the risk of atherothrombotic event risk.
Symptomatic atherothrombotic events such as acute myocardial infarction occur when organ perfusing arterial branch was occluded by thrombi. The diameter of organ perfusing vessels is substantially larger than a single cell of platelet. Indeed, the diameter of platelets is just 2–5 μm, while the diameter of myocardial perfusing coronary arterial branches is 2–3 mm. The size of vessel diameter is typically 1000 more than the size of platelet diameter. It is nonrealistic to imagine that coronary arterial branches were occluded by platelet thrombi. Indeed, when coronary arterial thrombi causing myocardial infarction are aspirated by thrombo-aspiration therapy, the main component of occlusive thrombi was fibrin (Figure 3). It is noteworthy that fibrin fibrils are detected around activated platelets (Figure 3 is the product in collaboration with Prof. Yujiro Asada at Miyazaki University).
Major components of thrombi causing acute myocardial infarction. Sample thrombi were aspirated from patients with acute myocardial infarction. The main results and study protocols were published elsewhere [53]. Here, electron microscopy results are shown. Fibrin fibrils could be seen around activated platelets (arrow).
The lipid components of activated platelet changed from the ones at the quiescent state. Negatively charged phospholipids appeared on the surface of activated platelets [22]. Then, various coagulation factors accumulated around the lipid to form prothrombin complex. On the activated platelet, thrombin generation occurs extremely efficiently. Indeed, thrombin generation rate in the absence of activated platelet and tissue factor is almost 0 as compared to that in its presence. At the site of atheroma rupture, large enough fibrin thrombi were formed as a result of the accumulation of activated platelet and exposure of tissue factor from the ruptured atheroma. Tissue factor accumulated in the atheroma is generated from inflammatory cells, which migrated into the atheroma. In the animal study, dietary lipid restriction reduces the amount of tissue factor accumulated in the atheroma [30]. The clinical factor of the reduction of the onset of myocardial infarction by the use of lipid-lowering therapy [31] may be related to reduction of lipid accumulation and subsequent reduction in tissue factor accumulated in the atheroma. Moreover, there are several publications indicating the impact of food intake for the lipid component of blood cells [23, 24]. The rate of fibrin formation at the site of endothelial damage and platelet accumulation should be modified by food from both activated platelet-derived procoagulant activity and the amount of tissue factors accumulated in the atheroma.
The process of thrombus formation at the site of endothelial injury is complex. We have attempted to develop the process model of thrombus formation as shown in Figure 4 [32]. The model is still simple but includes various physically and chemically different events. First, the model implemented the effect of blood flow, which is a purely physical phenomenon. Second, the model includes platelet adhesion and activation. Platelet adhesion is implemented to be medicated by its GPIbα binding with von Willebrand factor (VWF) (① in Figure 4). GPIbα binding with VWF is a chemical phenomenon, but the binding force is a physical one. We have implemented both in the same model. Platelets were implemented to be activated to change their biological roles (② in Figure 4). This process is a biological process. The detailed process model of platelet activation was published elsewhere [33]. Briefly, platelets were settled to be captured by VWF under blood flow condition. Collagen exposed at the site of endothelial injury also interacts with platelet and contributed to platelet activation through its receptor, namely, GPVI [34]. Then, activated platelet was settled to have stronger capacity to bind with injured vessel wall, cohesion each other, and possess the capacity to express coagulogenic phospholipids. Then, prothrombin conversion to thrombin was settled to occur only on the surface of activated platelets (③ in Figure 4). Thrombin function is neutralized promptly by its interaction with antithrombin III. Thrombin implemented to have function to convert fibrinogen to fibrin (④ in Figure 4) and further activated platelet through thrombin receptor stimulations [35].
Coupling model of blood flow, platelet, coagulation, and fibrinolysis. Thrombus formation at the site of endothelial injury is modeled. Nonactivated platelets (NP) adhered at the site of endothelial injury through von Willebrand factor (VWF) and collagen are exposed there. NP become activated platelets (AP) by their interaction with VWF/collagen (①). AP has a potential to convert prothrombin to thrombin on their membrane surface (②). After production of thrombin from prothrombin (③), thrombin converts soluble fibrinogen to fibrin thrombi. (④) thrombin also has a function to further activate platelets through thrombin receptor stimulation. (⑤) Fibrinolytic system is also incorporated in this model. Functional endothelial cells constitutively release both tissue-type plasminogen activator (t-PA: ⑥) and plasminogen activator inhibitor (PAI)-1 (⑦). T-PA converts plasminogen to plasmin, which has fibrinolytic activity (⑧) unless inactivated by binding with PAI-1. Plasmin is a strong enzyme able to degrade fibrin. Its function is immediately neutralized by its binding with a2-plasmin inhibitor to form plasmin a2-plasmin inhibitor complex (PIC: ⑨).
There are several coagulation factors, the function of which is regulated strongly by food intake. Gla-domain of coagulation factors plays crucial roles in the accumulation of coagulation factors around exposed negatively charged phospholipids on activated platelets [36]. Gla-domain also plays crucial roles for enzymatic function of coagulation factors. Carboxylation of Gla-domain is mediated by vitamin K. Thus, coagulation cascade does not work well in the absence of vitamin K or in patients taking vitamin K inhibitor. It is noteworthy that there are many foods including fermented food that are known to contain abundant vitamin K. Strict food restriction is necessary to keep the anticoagulant effects of vitamin K inhibitors. Recently, a larger load of vitamin K on health is cautioned [37].
The amount of fibrin formed at the site of endothelial injury was reduced by the effect of intrinsic fibrinolysis. Fibrinolysis is a complex pathway, but the details of which is simplified to be incorporated as shown in Figure 4. Vascular endothelial cells have balanced roles for fibrinolysis by releasing both fibrinolytic tissue-type plasminogen activator (t-PA: ⑥) and the one has antifibrinolytic effects of plasminogen activator inhibitor (PAI)-1 (⑦). Both of them are constitutively released from endothelial cells. But the rates of their releases were individually controlled in individual endothelial cells. When the rate of t-PA release increases, the amount of fibrin formed around the endothelial cells becomes smaller. It becomes larger in the case when the rate of PAI-1 release increases. Free t-PA has a potential to convert plasminogen to plasmin. (⑧) Plasmin is a strong protease, which can dissolve many functional proteins including fibrinogen. To avoid too much protein degradation, activity of plasmin is promptly neutralized by the function of α2-plasmin inhibitor (α2-PI: ⑨).
Previous publication suggested increased PAI-1 release after acute myocardial infarction and its role for the increased recurrence of myocardial infarction [38]. Animal experiments revealed that the food coloring agent of crocin reduces activity of PAI-1 and prevents thrombosis [39]. In human, increased PAI-1 activity is reported at the time of too much intake of fat [40]. Total fibrinolytic activity in humans is also reported to be low in obese patients [41]. Decreased fibrinolytic activity in patients taking too much lipid is one potential reason of increased risk of thrombosis in these patients.
There are many reports suggesting the increase/decrease in the risk of thrombosis by various food and beverage intake. Framingham study suggested that coffee consumption is related to lower risk of myocardial infarction [42]. However, the influence of coffee intake for the onset and recurrence of myocardial infarction is still under discussion because other reports suggested higher rate of sudden cardiac death in coffee intake in patients after myocardial infarction [43]. People have consensus that food intake should influence the risk of arterial and venous thrombosis. The problem is that it is still hard to state which food reduces/increases the risk of thrombosis.
Old epidemiological studies suggested that the risk of myocardial infarction increased in Japanese people who immigrated to Hawaii or California than that of the ones staying in Japan. They have the same genetic background. Environmental factors including food should contribute to the change in the risk of population when moved to the US than staying in Japan. Lower cardiovascular death rate in Japan is still noted in the international registry of patients with atherothrombosis or non-valvular atrial fibrillation. Despite epidemiological data, it is still hard to identify what food specifically modulated the rate of thrombosis.
There are many specific diets that potentially influence thrombotic risk. Among them, sodium intake should be one of the most established factors to avoid cardiovascular diseases. Low sodium intake clearly decreases the risk of heart failure [44], but its direct effects for thrombosis is still to be elucidated. Mediterranean diet is also related to lower risk of cardiovascular diseases [45]. But it is still difficult to identify the specific content of Mediterranean diet related to the reduction in the risk of CV disease. A plant-based diet seems beneficial in reducing the risk of cardiovascular disease, but it has both good qualities and bad qualities [46]. The relationship between food and the risk of cardiovascular diseases (mostly arterial thrombosis) is complex.
A recent publication suggested the positive correlation between red and processed meat intake and risk of cardiovascular diseases. This study also suggested the negative relationship between the intake of yogurt, cheese, and eggs and CV disease risk [47]. The observation study is useful to find potential contributing factors but still includes many potential biases. Just like drug or medical intervention, randomized trials comparing a variety of food intake with hard endpoint of cardiovascular death, myocardial infarction, and ischemic stroke will give us more insight. However, in reality, it is hard to design such trials because people have the right to eat whatever they like. It is hard to make a restriction in food intake for a long period of time. The combination of observational study and the study to clarify the mechanism will give us the best available evidence now.
Metabolic syndrome is characterized as the presence of three apparent characteristics including visceral obesity manifested as increasing waist circumference, dyslipidemia, hypertension, and high blood glucose. Underlining pathophysiology is insulin resistance and lipid accumulation. It is noteworthy that various cytokines (adipocytokines) were identified from adipose tissue. Adiponectin is the one identified as factor reducing the risk of thrombosis by preventing endothelial dysfunction [48]. Indeed, decreased plasma concentration of adiponectin observed in obese patients may suggest the potential regulatory role of adiponectin for the onset of thrombotic diseases [49]. Despite difficulty in understanding the precise relationship among various cytokines and adiponectin [50], an apparent link between metabolic syndrome and decreased adiponectin is noteworthy. Various parameters for coagulation and fibrinolysis are also influenced in metabolic syndrome patients [51]. It is reasonable to recommend regular exercise to prevent metabolic syndrome and future onset of thrombosis [52].
Obviously, food intake influences deeply the risk of thrombotic disease such as arterial and venous thrombotic diseases. Deeply reliable population-based clinical trials or nicely designed registry studies are awaited. Precise understand the mechanism of thrombotic disease from hard science such as re-construction of biological phenomena from the physical movement of atoms.
Shinya Goto acknowledges financial support from MEXT/JSPS KAKENHI 17 K19669, 18H01726, and 19H03661. SG acknowledges independent research grant support from Bristol-Myers Squibb (33999603). SG also acknowledges grant support from Vehicle Racing Commemorative Foundation and Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering. SG received research funding from Sanofi, Pfizer, and Ono.
Book - collection of Works distributed in a book format, whose selection, coordination, preparation, and arrangement has been performed and published by IntechOpen, and in which the Work is included in its entirety in an unmodified form along with one or more other contributions, each constituting separate and independent sections, but together assembled into a collective whole.
",metaTitle:"Attribution Policy",metaDescription:"DEFINITION OF TERMS",metaKeywords:null,canonicalURL:"/page/attribution-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\\n\\nAttribution – appropriate credit for the used Work or book.
\\n\\nCreative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\\n\\nWith the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\\n\\nIn case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
\\n\\nAll rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\\n\\nA Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\\n\\nIn instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\\n\\nEvery single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\\n\\nIndividual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\\n\\nEvery single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\\n\\nIn the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\\n\\nIntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\\n\\nAll these rules apply to BOTH online and offline use.
\\n\\nParts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
\\n\\nAll the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
\\n\\nPolicy last updated: 2016-06-09
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\n\nAttribution – appropriate credit for the used Work or book.
\n\nCreative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\n\nWith the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\n\nIn case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
\n\nAll rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\n\nA Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\n\nIn instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\n\nEvery single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\n\nIndividual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\n\nEvery single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\n\nIn the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\n\nIntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\n\nAll these rules apply to BOTH online and offline use.
\n\nParts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
\n\nAll the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
\n\nPolicy last updated: 2016-06-09
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5766},{group:"region",caption:"Middle and South America",value:2,count:5227},{group:"region",caption:"Africa",value:3,count:1717},{group:"region",caption:"Asia",value:4,count:10367},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15790}],offset:12,limit:12,total:118189},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"1",sort:"dateEndThirdStepPublish"},books:[{type:"book",id:"10231",title:"Proton Therapy",subtitle:null,isOpenForSubmission:!0,hash:"f4a9009287953c8d1d89f0fa9b7597b0",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10231.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10652",title:"Visual Object Tracking",subtitle:null,isOpenForSubmission:!0,hash:"96f3ee634a7ba49fa195e50475412af4",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10652.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10653",title:"Optimization Algorithms",subtitle:null,isOpenForSubmission:!0,hash:"753812dbb9a6f6b57645431063114f6c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10653.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10655",title:"Motion Planning",subtitle:null,isOpenForSubmission:!0,hash:"809b5e290cf2dade9e7e0a5ae0ef3df0",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10655.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10657",title:"Service Robots",subtitle:null,isOpenForSubmission:!0,hash:"5f81b9eea6eb3f9af984031b7af35588",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10657.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10662",title:"Pedagogy",subtitle:null,isOpenForSubmission:!0,hash:"c858e1c6fb878d3b895acbacec624576",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10662.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10673",title:"The Psychology of Trust",subtitle:null,isOpenForSubmission:!0,hash:"1f6cac41fd145f718ac0866264499cc8",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10673.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10675",title:"Hydrostatics",subtitle:null,isOpenForSubmission:!0,hash:"c86c2fa9f835d4ad5e7efd8b01921866",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10675.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10677",title:"Topology",subtitle:null,isOpenForSubmission:!0,hash:"85eac84b173d785f989522397616124e",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10677.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10678",title:"Biostatistics",subtitle:null,isOpenForSubmission:!0,hash:"f63db439474a574454a66894db8b394c",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10678.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10679",title:"Mass Production",subtitle:null,isOpenForSubmission:!0,hash:"2dae91102099b1a07be1a36a68852829",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10679.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10684",title:"Biorefineries",subtitle:null,isOpenForSubmission:!0,hash:"23962c6b77348bcbf247c673d34562f6",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10684.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:6},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:6},{group:"topic",caption:"Business, Management and Economics",value:7,count:5},{group:"topic",caption:"Chemistry",value:8,count:1},{group:"topic",caption:"Computer and Information Science",value:9,count:5},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:3},{group:"topic",caption:"Engineering",value:11,count:6},{group:"topic",caption:"Environmental Sciences",value:12,count:4},{group:"topic",caption:"Immunology and Microbiology",value:13,count:2},{group:"topic",caption:"Mathematics",value:15,count:3},{group:"topic",caption:"Medicine",value:16,count:27},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:4},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1}],offset:12,limit:12,total:86},popularBooks:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9043",title:"Parenting",subtitle:"Studies by an Ecocultural and Transactional Perspective",isOpenForSubmission:!1,hash:"6d21066c7438e459e4c6fb13217a5c8c",slug:"parenting-studies-by-an-ecocultural-and-transactional-perspective",bookSignature:"Loredana Benedetto and Massimo Ingrassia",coverURL:"https://cdn.intechopen.com/books/images_new/9043.jpg",editors:[{id:"193200",title:"Prof.",name:"Loredana",middleName:null,surname:"Benedetto",slug:"loredana-benedetto",fullName:"Loredana Benedetto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5229},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8098",title:"Resources of Water",subtitle:null,isOpenForSubmission:!1,hash:"d251652996624d932ef7b8ed62cf7cfc",slug:"resources-of-water",bookSignature:"Prathna Thanjavur Chandrasekaran, Muhammad Salik Javaid, Aftab Sadiq",coverURL:"https://cdn.intechopen.com/books/images_new/8098.jpg",editedByType:"Edited by",editors:[{id:"167917",title:"Dr.",name:"Prathna",middleName:null,surname:"Thanjavur Chandrasekaran",slug:"prathna-thanjavur-chandrasekaran",fullName:"Prathna Thanjavur Chandrasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editedByType:"Edited by",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8415",title:"Extremophilic Microbes and Metabolites",subtitle:"Diversity, Bioprospecting and Biotechnological Applications",isOpenForSubmission:!1,hash:"93e0321bc93b89ff73730157738f8f97",slug:"extremophilic-microbes-and-metabolites-diversity-bioprospecting-and-biotechnological-applications",bookSignature:"Afef Najjari, Ameur Cherif, Haïtham Sghaier and Hadda Imene Ouzari",coverURL:"https://cdn.intechopen.com/books/images_new/8415.jpg",editedByType:"Edited by",editors:[{id:"196823",title:"Dr.",name:"Afef",middleName:null,surname:"Najjari",slug:"afef-najjari",fullName:"Afef Najjari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"98",title:"Astronomy and Astrophysics",slug:"astronomy-and-astrophysics",parent:{title:"Earth and Planetary Sciences",slug:"earth-and-planetary-sciences"},numberOfBooks:4,numberOfAuthorsAndEditors:89,numberOfWosCitations:91,numberOfCrossrefCitations:40,numberOfDimensionsCitations:74,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"astronomy-and-astrophysics",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7338",title:"Planetology",subtitle:"Future Explorations",isOpenForSubmission:!1,hash:"d52566a2f61bb3d7021ed630a149e1e6",slug:"planetology-future-explorations",bookSignature:"Bryan Palaszewski",coverURL:"https://cdn.intechopen.com/books/images_new/7338.jpg",editedByType:"Edited by",editors:[{id:"279275",title:"M.Sc.",name:"Bryan",middleName:null,surname:"Palaszewski",slug:"bryan-palaszewski",fullName:"Bryan Palaszewski"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8444",title:"Lunar Science",subtitle:null,isOpenForSubmission:!1,hash:"f1dcf511a174e8ec89d97ca8c0c6146a",slug:"lunar-science",bookSignature:"Yann H. Chemin",coverURL:"https://cdn.intechopen.com/books/images_new/8444.jpg",editedByType:"Edited by",editors:[{id:"270578",title:"Dr.",name:"Yann",middleName:"H.",surname:"Chemin",slug:"yann-chemin",fullName:"Yann Chemin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1629",title:"Astrophysics",subtitle:null,isOpenForSubmission:!1,hash:"95209a68cff9bc045b51611c513b63bd",slug:"astrophysics",bookSignature:"Ibrahim Kucuk",coverURL:"https://cdn.intechopen.com/books/images_new/1629.jpg",editedByType:"Edited by",editors:[{id:"102957",title:"Prof.",name:"İbrahim",middleName:null,surname:"Küçük",slug:"ibrahim-kucuk",fullName:"İbrahim Küçük"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1617",title:"Exploring the Solar Wind",subtitle:null,isOpenForSubmission:!1,hash:"7695d3592f3bb8f5c0a52de901949a74",slug:"exploring-the-solar-wind",bookSignature:"Marian Lazar",coverURL:"https://cdn.intechopen.com/books/images_new/1617.jpg",editedByType:"Edited by",editors:[{id:"107684",title:"Dr.",name:"Marian",middleName:null,surname:"Lazar",slug:"marian-lazar",fullName:"Marian Lazar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,mostCitedChapters:[{id:"32544",doi:"10.5772/37359",title:"The Polar Cap PC Indices: Relations to Solar Wind and Global Disturbances",slug:"the-polar-cap-pc-indices-relations-to-solar-wind-and-global-disturbances",totalDownloads:2700,totalCrossrefCites:11,totalDimensionsCites:13,book:{slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"Peter Stauning",authors:[{id:"112396",title:"MSc.",name:"Peter",middleName:null,surname:"Stauning",slug:"peter-stauning",fullName:"Peter Stauning"}]},{id:"32539",doi:"10.5772/39281",title:"Suprathermal Particle Populations in the Solar Wind and Corona",slug:"suprathermal-particle-populations-in-the-solar-wind-and-corona",totalDownloads:2801,totalCrossrefCites:7,totalDimensionsCites:10,book:{slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"M. Lazar, R. Schlickeiser and S. Poedts",authors:[{id:"107684",title:"Dr.",name:"Marian",middleName:null,surname:"Lazar",slug:"marian-lazar",fullName:"Marian Lazar"}]},{id:"32533",doi:"10.5772/37908",title:"Measuring the Isotopic Composition of Solar Wind Noble Gases",slug:"measuring-the-isotopic-composition-of-solar-wind-noble-gases",totalDownloads:2266,totalCrossrefCites:6,totalDimensionsCites:8,book:{slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"Alex Meshik, Charles Hohenberg, Olga Pravdivtseva and Donald Burnett",authors:[{id:"114740",title:"Prof.",name:"Alexander",middleName:null,surname:"Meshik",slug:"alexander-meshik",fullName:"Alexander Meshik"},{id:"115300",title:"Prof.",name:"Donald",middleName:null,surname:"Burnett",slug:"donald-burnett",fullName:"Donald Burnett"},{id:"115301",title:"Prof.",name:"Charles",middleName:null,surname:"Hohenberg",slug:"charles-hohenberg",fullName:"Charles Hohenberg"},{id:"115302",title:"Dr.",name:"Olga",middleName:null,surname:"Pravdivtseva",slug:"olga-pravdivtseva",fullName:"Olga Pravdivtseva"}]}],mostDownloadedChaptersLast30Days:[{id:"32544",title:"The Polar Cap PC Indices: Relations to Solar Wind and Global Disturbances",slug:"the-polar-cap-pc-indices-relations-to-solar-wind-and-global-disturbances",totalDownloads:2702,totalCrossrefCites:11,totalDimensionsCites:13,book:{slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"Peter Stauning",authors:[{id:"112396",title:"MSc.",name:"Peter",middleName:null,surname:"Stauning",slug:"peter-stauning",fullName:"Peter Stauning"}]},{id:"32539",title:"Suprathermal Particle Populations in the Solar Wind and Corona",slug:"suprathermal-particle-populations-in-the-solar-wind-and-corona",totalDownloads:2803,totalCrossrefCites:7,totalDimensionsCites:10,book:{slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"M. Lazar, R. Schlickeiser and S. Poedts",authors:[{id:"107684",title:"Dr.",name:"Marian",middleName:null,surname:"Lazar",slug:"marian-lazar",fullName:"Marian Lazar"}]},{id:"70129",title:"Introductory Chapter: Planetology",slug:"introductory-chapter-planetology",totalDownloads:208,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"planetology-future-explorations",title:"Planetology",fullTitle:"Planetology - Future Explorations"},signatures:"Bryan Palaszewski",authors:[{id:"279275",title:"M.Sc.",name:"Bryan",middleName:null,surname:"Palaszewski",slug:"bryan-palaszewski",fullName:"Bryan Palaszewski"}]},{id:"34268",title:"Visualization Methods for Numerical Astrophysics",slug:"visualization-methods-for-numerical-astrophysics",totalDownloads:1946,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"astrophysics",title:"Astrophysics",fullTitle:"Astrophysics"},signatures:"Werner Benger, Markus Haider, Harald Höller, Dominik Steinhauser, Josef Stöckl, Biagio Cosenza and Marcel Ritter",authors:[{id:"90557",title:"Dr.",name:"Werner",middleName:null,surname:"Benger",slug:"werner-benger",fullName:"Werner Benger"},{id:"112252",title:"MSc.",name:"Markus",middleName:null,surname:"Haider",slug:"markus-haider",fullName:"Markus Haider"},{id:"112253",title:"Dr.",name:"Josef",middleName:null,surname:"Stoeckl",slug:"josef-stoeckl",fullName:"Josef Stoeckl"},{id:"112254",title:"Dr.",name:"Biagio",middleName:null,surname:"Cosenza",slug:"biagio-cosenza",fullName:"Biagio Cosenza"},{id:"112257",title:"MSc.",name:"Marcel",middleName:null,surname:"Ritter",slug:"marcel-ritter",fullName:"Marcel Ritter"},{id:"112258",title:"MSc.",name:"Dominik",middleName:null,surname:"Steinhauser",slug:"dominik-steinhauser",fullName:"Dominik Steinhauser"},{id:"128849",title:"MSc.",name:"Harald",middleName:null,surname:"Hoeller",slug:"harald-hoeller",fullName:"Harald Hoeller"}]},{id:"32543",title:"Ground-Based Monitoring of the Solar Wind Geoefficiency",slug:"ground-based-monitoring-of-the-solar-wind-geoefficiency",totalDownloads:2019,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"Oleg Troshichev",authors:[{id:"116123",title:"Prof.",name:"Oleg",middleName:null,surname:"Troshichev",slug:"oleg-troshichev",fullName:"Oleg Troshichev"}]},{id:"34257",title:"Nuclear Excitation Processes in Astrophysical Plasmas",slug:"nuclear-excitation-processes-in-astrophysical-plasmas",totalDownloads:2016,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"astrophysics",title:"Astrophysics",fullTitle:"Astrophysics"},signatures:"G. Gosselin, P. Mohr, V. Méot and P. Morel",authors:[{id:"109302",title:"Mr.",name:"Gilbert",middleName:null,surname:"Gosselin",slug:"gilbert-gosselin",fullName:"Gilbert Gosselin"},{id:"109409",title:"Dr.",name:"Vincent",middleName:null,surname:"Meot",slug:"vincent-meot",fullName:"Vincent Meot"},{id:"109410",title:"Dr.",name:"Pascal",middleName:null,surname:"Morel",slug:"pascal-morel",fullName:"Pascal Morel"},{id:"112136",title:"Dr.",name:"Peter",middleName:null,surname:"Mohr",slug:"peter-mohr",fullName:"Peter Mohr"}]},{id:"32535",title:"Multifractal Turbulence in the Heliosphere",slug:"multifractal-turbulence-in-the-heliosphere",totalDownloads:2032,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"Wiesław M. Macek",authors:[{id:"111245",title:"Prof.",name:"Wieslaw",middleName:null,surname:"Macek",slug:"wieslaw-macek",fullName:"Wieslaw Macek"}]},{id:"32546",title:"Turbulence in the Magnetosheath and the Problem of Plasma Penetration Inside the Magnetosphere",slug:"turbulence-in-the-magnetosheath-and-the-problem-of-plasma-penetration-inside-the-magnetosphere",totalDownloads:1921,totalCrossrefCites:0,totalDimensionsCites:6,book:{slug:"exploring-the-solar-wind",title:"Exploring the Solar Wind",fullTitle:"Exploring the Solar Wind"},signatures:"Elizaveta E. Antonova, Maria S. Pulinets, Maria O. Riazantseva, Svetlana S. Znatkova, Igor P. Kirpichev and Marina V. Stepanova",authors:[{id:"108722",title:"Prof.",name:"Elizaveta",middleName:null,surname:"Antonova",slug:"elizaveta-antonova",fullName:"Elizaveta Antonova"},{id:"108731",title:"Dr.",name:"Maria",middleName:null,surname:"Riazantseva",slug:"maria-riazantseva",fullName:"Maria Riazantseva"}]},{id:"34263",title:"The Lane-Emden-Fowler Equation and Its Generalizations - Lie Symmetry Analysis",slug:"the-lane-emden-equation-and-its-generalizations",totalDownloads:3486,totalCrossrefCites:1,totalDimensionsCites:0,book:{slug:"astrophysics",title:"Astrophysics",fullTitle:"Astrophysics"},signatures:"Chaudry Masood Khalique",authors:[{id:"94177",title:"Dr.",name:"Chaudry",middleName:"Masood",surname:"Khalique",slug:"chaudry-khalique",fullName:"Chaudry Khalique"}]},{id:"65534",title:"Solar System Exploration Augmented by In Situ Resource Utilization: Lunar Base Issues",slug:"solar-system-exploration-augmented-by-in-situ-resource-utilization-lunar-base-issues",totalDownloads:494,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"lunar-science",title:"Lunar Science",fullTitle:"Lunar Science"},signatures:"Bryan Palaszewski",authors:[{id:"279275",title:"M.Sc.",name:"Bryan",middleName:null,surname:"Palaszewski",slug:"bryan-palaszewski",fullName:"Bryan Palaszewski"}]}],onlineFirstChaptersFilter:{topicSlug:"astronomy-and-astrophysics",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"book.detail",path:"/books/elements-of-bioeconomy",hash:"",query:{},params:{book:"elements-of-bioeconomy"},fullPath:"/books/elements-of-bioeconomy",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()