\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3283",leadTitle:null,fullTitle:"Skin Grafts",title:"Skin Grafts",subtitle:null,reviewType:"peer-reviewed",abstract:"Split thickness skin grafting procedure is a simple but essential and important one to achieve closure of a full thickness or deep partial thickness skin defect. It needs to be performed with care and precision for successful outcome. \nThe present publication is devoted to skin grafts. Three important components of this procedure are preparation of wound bed, fixation of skin grafts to the recipient area to improve possibility of graft take and management of skin graft donor area for both full thickness and split thickness grafts. The chapters have been distributed in these three sections.",isbn:null,printIsbn:"978-953-51-0973-0",pdfIsbn:"978-953-51-7081-5",doi:"10.5772/45962",price:119,priceEur:129,priceUsd:155,slug:"skin-grafts",numberOfPages:114,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"51201608d5c5d7ff6f47e5afd2abdb9f",bookSignature:"Madhuri Gore",publishedDate:"February 6th 2013",coverURL:"https://cdn.intechopen.com/books/images_new/3283.jpg",numberOfDownloads:20257,numberOfWosCitations:11,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:16,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:32,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2012",dateEndSecondStepPublish:"May 4th 2012",dateEndThirdStepPublish:"August 8th 2012",dateEndFourthStepPublish:"November 6th 2012",dateEndFifthStepPublish:"December 6th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"157243",title:"Dr.",name:"Madhuri",middleName:null,surname:"Gore",slug:"madhuri-gore",fullName:"Madhuri Gore",profilePictureURL:"https://mts.intechopen.com/storage/users/157243/images/system/157243.png",biography:"Dr. Madhuri Gore, a former Professor and Chief of Surgery at Lokmanya Tilak Municipal Medical College and General Hospital (LTMGH), India, is presently a consultant general surgeon in Mumbai, India. Her areas of interest are burns, non-burn trauma and wounds, and venous diseases. An acknowledged teacher and sought-after speaker, Dr. Gore established the first cadaver skin bank in India. She is an avid researcher and has been the chief investigator for more than twenty-five national and international clinical trials. She has more than seventy-five publications in national and international journals to her credit and has contributed seventeen chapters to various books. She has been honored with several awards, prizes, scholarships, and orations for her contribution to the fields of her special interest.",institutionString:"Zen Hospital, Mumbai",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1152",title:"Reconstructive Surgery",slug:"reconstructive-surgery"}],chapters:[{id:"41232",title:"Hydrosurgery-System® in Burn Surgery – Indications and Applications",doi:"10.5772/51851",slug:"hydrosurgery-system-in-burn-surgery-indications-and-applications",totalDownloads:2033,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:null,signatures:"Thomas Rappl",downloadPdfUrl:"/chapter/pdf-download/41232",previewPdfUrl:"/chapter/pdf-preview/41232",authors:[{id:"155384",title:"Dr.",name:"Thomas",surname:"Rappl",slug:"thomas-rappl",fullName:"Thomas Rappl"}],corrections:null},{id:"42567",title:"Evaluation of Skin Grafting Procedure in Burnt Patients",doi:"10.5772/54184",slug:"evaluation-of-skin-grafting-procedure-in-burnt-patients",totalDownloads:2557,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Madhuri A. 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It brings together discussions from leading researchers and scholars in the field of land use change and sustainability from five different countries including the USA, Ethiopia, Guyana, Taiwan, and Indonesia. Based on empirical research and case studies, the book is divided into two sections. The first section is subdivided into four chapters and discusses land use sustainability in the Northern Great Plains of the USA; effects of rural land use and tenure on sustainable management of mangroves in Corentyne, Guyana; the property formation process in peri-urban areas of Ethiopia; and the effects of green energy production on farmlands in the Yulin County of Taiwan. The second section of the book is subdivided into two chapters and discusses cases pertaining to land use mapping and sustainability including land cover/land use mapping using soft computing techniques with optimized features; and applying systems analysis to evaluate Jelutung as option for sustainable use of peat lands in Central Kalimantan, Indonesia. The book is insightful, thought provoking, concise, and easy to understand. It could serve as an important reference material on land use change and sustainability.",isbn:"978-1-78984-300-2",printIsbn:"978-1-78984-299-9",pdfIsbn:"978-1-83880-732-0",doi:"10.5772/intechopen.77843",price:119,priceEur:129,priceUsd:155,slug:"land-use-change-and-sustainability",numberOfPages:106,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"6b3aee3b93d95ecd84c41753486f7a83",bookSignature:"Seth Appiah-Opoku",publishedDate:"February 26th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8013.jpg",keywords:null,numberOfDownloads:4680,numberOfWosCitations:0,numberOfCrossrefCitations:4,numberOfDimensionsCitations:8,numberOfTotalCitations:12,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 9th 2018",dateEndSecondStepPublish:"October 30th 2018",dateEndThirdStepPublish:"December 29th 2018",dateEndFourthStepPublish:"March 19th 2019",dateEndFifthStepPublish:"May 18th 2019",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"4 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"137858",title:"Dr.",name:"Seth",middleName:null,surname:"Appiah-Opoku",slug:"seth-appiah-opoku",fullName:"Seth Appiah-Opoku",profilePictureURL:"https://mts.intechopen.com/storage/users/137858/images/system/137858.jpg",biography:"Dr. Seth Appiah-Opoku is a Professor of Geography at the University of Alabama, Tuscaloosa, AL, USA. He teaches World Regional Geography, Regional Geography of Africa, Environmental Management, Land Use Regulation, Principles of Planning, Regional Planning and Analysis, and also the Ghana Summer Abroad course. He is a member of the American Institute of Certified Planners and the editor of three books - The Need for Indigenous Knowledge in Environmental Impact Assessment: The Case of Ghana (Edwin Mellen Press, NY, June 2005), Environmental Land Use Planning (IntechOpen, 2012), and International Development (IntechOpen, 2017). His research focuses on international development, urban planning, ecotourism, environmental impact assessment, and resource development. He serves on the Editorial Boards of the Journal of Environmental Impact Assessment Review and the Environment and Social Psychology Journal. He also served as the editor of the Journal of African Geographical Review from 2016 to 2018. He has published scholarly articles in several renowned journals including Environmental Management, Society and Natural Resources, Environmental Impact Assessment Review, Journal of Cultural Geography, and Plan Canada. He served on the Technical Advisory Team that advised the government of Ghana on the preparation of a 40-year development plan for the country.",institutionString:"University of Alabama, Tuscaloosa",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"University of Alabama, Tuscaloosa",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"849",title:"Landscape Ecology",slug:"landscape-ecology"}],chapters:[{id:"65861",title:"Soil and Land-Use Change Sustainability in the Northern Great Plains of the USA",slug:"soil-and-land-use-change-sustainability-in-the-northern-great-plains-of-the-usa",totalDownloads:1032,totalCrossrefCites:2,authors:[{id:"37140",title:"Prof.",name:"David",surname:"Clay",slug:"david-clay",fullName:"David Clay"},{id:"87430",title:"Prof.",name:"Sharon",surname:"Clay",slug:"sharon-clay",fullName:"Sharon Clay"},{id:"256000",title:"Dr.",name:"Alexander",surname:"Smart",slug:"alexander-smart",fullName:"Alexander Smart"},{id:"282796",title:null,name:"Deepak",surname:"Joshi",slug:"deepak-joshi",fullName:"Deepak Joshi"},{id:"282830",title:"Dr.",name:"Umakant",surname:"Mishra",slug:"umakant-mishra",fullName:"Umakant Mishra"},{id:"282832",title:"Dr.",name:"Tulsi",surname:"Kharel",slug:"tulsi-kharel",fullName:"Tulsi Kharel"}]},{id:"68023",title:"Urban Built-Up Property Formation Process in the Peri-Urban Areas of Ethiopia",slug:"urban-built-up-property-formation-process-in-the-peri-urban-areas-of-ethiopia",totalDownloads:804,totalCrossrefCites:0,authors:[{id:"285509",title:"Dr.",name:"Achamyeleh",surname:"Adam",slug:"achamyeleh-adam",fullName:"Achamyeleh Adam"}]},{id:"69702",title:"Effects of Rural Land Tenure System on Mangroves Management in Corentyne, Guyana",slug:"effects-of-rural-land-tenure-system-on-mangroves-management-in-corentyne-guyana",totalDownloads:748,totalCrossrefCites:1,authors:[{id:"280866",title:"Ms.",name:"Linda",surname:"Johnson-Bhola",slug:"linda-johnson-bhola",fullName:"Linda Johnson-Bhola"}]},{id:"66795",title:"The Effects of Green Energy Production on Farmland: A Case Study in Yunlin County, Taiwan",slug:"the-effects-of-green-energy-production-on-farmland-a-case-study-in-yunlin-county-taiwan",totalDownloads:840,totalCrossrefCites:0,authors:[{id:"206814",title:"Dr.",name:"Shih-Yuan",surname:"Lin",slug:"shih-yuan-lin",fullName:"Shih-Yuan Lin"},{id:"215320",title:"Prof.",name:"Yu-Hsin",surname:"Tsai",slug:"yu-hsin-tsai",fullName:"Yu-Hsin Tsai"},{id:"282555",title:"Dr.",name:"Stephan",surname:"Van Gasselt",slug:"stephan-van-gasselt",fullName:"Stephan Van Gasselt"},{id:"283368",title:"Prof.",name:"Tzu-Chin",surname:"Lin",slug:"tzu-chin-lin",fullName:"Tzu-Chin Lin"}]},{id:"68761",title:"Land Cover/Land Use Mapping Using Soft Computing Techniques with Optimized Features",slug:"land-cover-land-use-mapping-using-soft-computing-techniques-with-optimized-features",totalDownloads:608,totalCrossrefCites:0,authors:[{id:"281803",title:"Dr.",name:"Selvaraj",surname:"Rajesh",slug:"selvaraj-rajesh",fullName:"Selvaraj Rajesh"},{id:"282973",title:"Mrs.",name:"Gladima Nisia",surname:"T.",slug:"gladima-nisia-t.",fullName:"Gladima Nisia T."}]},{id:"66745",title:"Applying Systems Analysis to Evaluate Options for Sustainable Use of Peatlands in Central Kalimantan in Indonesia",slug:"applying-systems-analysis-to-evaluate-options-for-sustainable-use-of-peatlands-in-central-kalimantan",totalDownloads:648,totalCrossrefCites:1,authors:[{id:"287566",title:"MSc.",name:"Johan",surname:"Kieft",slug:"johan-kieft",fullName:"Johan Kieft"},{id:"287578",title:"MSc.",name:"Riska",surname:"Efrianti",slug:"riska-efrianti",fullName:"Riska Efrianti"},{id:"289497",title:"Dr.",name:"Andrea",surname:"Bassi",slug:"andrea-bassi",fullName:"Andrea Bassi"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"194666",firstName:"Nina",lastName:"Kalinic Babic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/194666/images/4750_n.jpg",email:"nina@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. 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Competitiveness drives the aerospace industries to investigate new technology solutions to address market pressure and high-tech demands. The global objective is to reduce to half the amount of fuel by 2020 and at least 70% less by 2025 with respect to the Boeing 777, one of the most efficient aircraft, which is made entirely of carbon fiber. The weight saving to increase payload and the reductions of the cost/time of the production cycle are imperative targets. For these reasons, aerospace companies, which are traditionally based on the use of metal alloys, have been focusing for past decade on composite materials. The main advantages of composites with respect to metals, that are resistance to corrosion and fatigue and high performance/weight ratios, are a set of qualities for winning the current and future aerospace applications. Obviously, this is possible only through the development of economically competitive technologies.
The Resin Transfer Molding (RTM) is one of the most promising technology available today. RTM is capable of making large complex three-dimensional part with high mechanical performance, tight dimensional tolerance and high surface finish. A good design by RTM leads to fabricate three-dimensional near-net-shape complex parts, offering production of cost-effective structural parts in medium-volume quantities using low cost tooling. In addition to these advantages, the problems of the joints, typical of the metal structures, can be eliminated by integration of inserts.
The final performances of a composite depend not only on the choice of the matrix and the fiber but also on the manufacturing process by which they are made. Since the starting of the composite life, the presence of imperfections due to manufacturing must be considered. Such imperfections can be already damage for the manufactured composite piece or lead to the damage quickly. The damage for composites can be defined as a change in the microstructure of the material that causes deterioration in the structural behavior of the component and sometimes its collapse. The damage in a composite structure can occur at the level of fibers and matrix as well.
The most common damage to the fibers is the interruption of their continuity. For example, fibers that are subject to load tend to align again inducing states of compression and tension on the matrix. These states may cause, in addition to a local decrease of the properties of the lamina, the breaking of the fibers themselves and the gap between fiber and matrix. In the assumption of an optimal stratification, fiber misalignment is caused during the manufacturing process by a bad balance of the process parameters that leads to the deformation of the fiber bundles. The fibers may also be distributed unevenly in the volume of the composite, and this generates intra-laminar shear stresses under operating conditions.
In the matrix, the damage is essentially correlated to the presence of porosity. The formation of microvoids between fibers and dry spots are potential starting points for propagating cracks or delaminations. The response of the component to delamination depends not only on the compatibility and surface tension between fibers and matrix but mainly on the compaction, and therefore also on the impregnation phases during the manufacturing process.
Comparing RTM with traditional manufacturing process applied in the aerospace industries (i.e. autoclave), the RTM technique results in a suitable alternative to the prepreg approach permitting high finish quality and controlled fiber directions. RTM reduces voids compared to hand lay-up so increasing component mechanical properties. In addition, component design by RTM process can compete with metal one when prepreg cannot be applied to manufacture a product. Hand lay-up requires a low initial investment, but it becomes more expensive (cost per product) than the other techniques due to recurring costs associated with direct labor and material waste. Compared with compression molding (CM), RTM requests lower tooling costs because of the absence of a press system to compact the preform. RTM seems to meet both low cost/high volume requirements of the automotive industry (500 to 50,000 parts per year) and low number/high performances (50 to 500 part per year) of the aerospace industry. In fact, RTM can guarantee the demanded performances for the aeronautical production: reduction of the mass, increase of the operating life, aimed design, reduction of the production times. Today an increasingly number of parts realized using RTM is observed due to the development of new resins and the preforming technology. In addition, such technique is suitable, with only small adjustments, for the realization of large, complex and thick-walled structures for use in infrastructures and military applications.
The RTM is a process with a rigid closed mold. Figure 1 summarizes the main steps for a simple case. The lamination sequence (preform) is draped in a half mold, then the mold is closed and the preform compacted. After that, the resin is injected using a positive gradient pressure through the gate points replacing the air entrapped within the preform. Usually, vacuum is applied at dedicated vents in order to favorite the air escape from the mold. When the resin reaches the vents, the gates are clamped and the preform is impregnated. At this point, the cure phase is considered to start. Finally, the mold is opened and the part removed. Especially for aerospace structures, an additional free-mold post-curing phase can be necessary in order to guarantee the polymerization of the matrix and release the internal thermal stress.
The closing mold step is characterized by the compaction of the fiber reinforcement, which permits to reach the desired thickness and design fiber volume fraction. The compaction changes the microstructure and the dimensions of the preform, producing large deformations and nonlinear viscoelastic effects. These effects are accompanied by a change in energy within the material, which causes the residual stresses due to the viscoelastic behavior of the fibers. However, during the impregnation phase a release of stress, probably due to the balance, occurs.
The injection phase must guarantee the complete impregnation of the preform: a bad impregnation of the fibers results in dry spot areas with missing adhesion between the layers, which makes the surface rough and irregular. If partial impregnation occurs in the proximity of a connecting zone among elements, it can cause a bad integration with a consequent loss of mechanical properties.
Sequence of the main steps of RTM process. From left to right: realization of the preform, deposition and draping of the preform in the mold cavity, closing mold, injection phase and curing phase; after the curing phase, the mold is opened and manufacred element is demolded.
The RTM process is governed by variables and parameters that are dependent on each other. Their combination affects the process and the quality of the finished product. Consequently, they need to be carefully determined. The most important parameters, which can not be neglected in the design, are pressure, temperature, viscosity, permeability, volume fraction, and filling time of the process. There are also a multitude of parameters that must be considered independently, such as the angle of attack of the nozzle, the orientation of the fibers, the paths of flow and shear rates, the stratification. In fact, the resin tends to flow more quickly in the fiber direction, thus the flow dynamic depends mainly on the type of fabric used and the number of overlapped layers. Sometimes it may be necessary to have a certain number of skins, not for structural reasons, but to obtain a homogeneous distribution of the resin. The thickness of the part to be manufactured can also affect the flow progress and the impregnation of the fibers, causing a high percentage of voids and dry spots. The thickness becomes a critical design constraint especially in the case of the inclusion of reinforcements and ribs.
The injection pressure determines the injection velocity of the resin into the mold, the hydraulic pressure and the holding and closing forces of the mold. Consequently, the injection velocity defines the filling time, which should not be too short to ensure an adequate impregnation of the fibers and, at the same time, the filling must be such as to avoid the risk of incurring in premature gelation of the resin. The injection pressure adjusts the distribution of the resin on the preform, which affects the formation of air voids in the matrix, the appearance surface and the mechanical properties of the finished product. Another phenomenon in which this parameter is relevant, together with the viscosity, is the so-called "fiber wash", i.e. the movement of the reinforcement inside the mold during the injection phase. In this case, the surface treatment of the fibers and especially the choice of the binder play a fundamental role. If the binder dissolves too quickly in contact with the resin, then fibers under the injection pressure can move freely.
The temperature is an extremely important process parameter and it is strictly related to the injection pressure and the viscosity of the resin. When the temperature increases, the filling time decreases and the working pressures are lower. When the temperature is low, the viscosity of the resin increases and it is necessary to increase the pressure to ensure the transfer of the resin itself.
As previously mentioned, the diffusion of RTM process in the aerospace industries is strictly related to the possibility of building net-shape 3D-complex structures. This possibility is given by the development of the preform technology. Preform is prepared separately and constitutes the skeleton of the final product, greatly simplifying the molding operations and reducing the time and cost of processing. When the production volumes is medium-high, an industrialized preform permits to amortize in a relatively short time the cost of equipment, even in a limited production, as required in the aerospace industry.
The textile methods are numerous. The choice of one method over the other depends on several factors: the processability, the feasibility of the geometry, the desired mechanical properties of the molded part, and the cost of production. Obviously, the preform affects strongly the performance required by the final application. The choice of the architecture of the fiber reinforcement depends on the required performance of the composite structure and the characteristics related to the process, such as permeability, compressibility and drape.
The preforms are formed weaving yarns or rovings. The terms used for the fiber comes from the textile tradition: a single fiber is a filament; a set of fibers produced simultaneously is called strand. Several parallel strands can be rolled up like a ribbon, called "roving" or "tows", or twisted and united as a strand, which is named "yarn". Generally, the yarns are typically not too complex because the excessive torque reduces the possibility of penetration of the resin in the cavities. Besides, a slight twist of the yarn compacts and raises the formation of composites with high fiber content.
Strands and yarns can be processed as woven roving and cloth. The first type uses effectively the resistance of the fibers, but it can produce composites with high resin content as the roving is not compacted. Woven roving is used to rapidly produce thick composites, because resin can fill them easily. Cloth is slightly less resistant than the roving because of the slight damage that is produced by rolling the fibers and also due to the twisting of the fibers themselves. The cloth is well impregnated from the resin and, as it is compact, high fiber content is obtained.
The weaving process can produce a wide variety of forms. The ratio between the number of filaments in the transverse direction (weft) and the number of filaments in the longitudinal direction (warp) may vary from nearly pure unidirectional, in which the number of filaments of the weft is the minimum required to hold together the fabric, up to the case of equal number of filaments in the warp and weft. In addition, there are hybrid fabrics with carbon fibers in the warp and glass fibers as weft. The weaving method influences the properties of the composite. In flat woven, warp and weft overlap in an alternating manner. In particular, weaving the warp passes through a number of fibers of the weft. These fabrics are better suitable for complex shapes, and their strength and stiffness are slightly higher because the fibers are straight on average. There are also more complex forms of weaving, with an angle of intersection fibers different from 90°. These methods are used to produce biaxial and multi-axial weaves. The complex fiber architectures can be obtained with the weaving method by interlacing and knitting the fibers along the three spatial directions; an example is shown in Figure 2. Different bi-axial layers can be also stitched. The stitching method consists on darning the layers with fibers (Figure 2). These are automated techniques that realize complex shapes and 3-D junctions in place of bolts and rivets. From the mechanical point of view, these methods can increase the resistance to fracture of the structure and reduce the progress of cracks by adopting high strength fibers in the z-direction. On the other hand, the stitching seams can produce local defects induced in the preform as a result of penetration of the wire and the needle. Further, the robotic system is very expensive and sometimes damage due to misalignment of fibers can occur.
The choice of the fiber reinforcement is carried out according to the mechanical requirements of the manufactured component. The types of fibers that can be used are many and with variable characteristics. During machining, the preform can be damaged, particularly when using glass fibers that are fragile and have a high friction coefficient (about 1 in the contact glass on glass). For this reason, immediately after production, the fibers are protected with a coating, "finish" or "size", which performs several functions: it acts as a binder to hold the fibers together, as a lubricant to reduce the coefficient of friction between fibers, and it improves the wettability of the fiber and the adhesion of the resin. Purpose of sizing is also to protect the fibers from the environment, mainly by moisture. These protective sizes are specific to each type of resin, since they must be dissolved from the resin itself. In the case of carbon fibers, the epoxy resin is also used as a protective finish.
Braiding method is another interesting textile process for aerospace structures. The braiding has high level of conformability to complex shapes and it is especially suitable for conical and cylindrical geometry. It regards 2D and 3D preforms. The high level of process automation reduces scrap and labour costs. More advantages of the braiding technique compared to standard tape and fabrics are strength in third dimension, improving fatigue resistance, more efficient distribution of mechanical stresses and the possibility to consider inserts during the preform realization. Despite of these characteristics, the braiding process requires the use of a mandrel and high initial cost for the preform engineering.
An important target of any textile process is obtaining the desired fiber volume fraction that is given by the design. It is very difficult to determine precisely the volume of reinforcement that must match the structural design with the manufacturing aspects. If the fibers are too compacted or their content is excessive, there is no sufficient space for the passage of the resin and the filling time becomes longer. Generally, the optimum volume of fibers is 60% of the product. An increase with respect to this value may cause a bad distribution of the resin and a dramatic drop of the mechanical properties of the manufactured component.
Examples of 3D weaving and stitching textile processes.
Braiding technology
Thermosetting resins are the matrix used in RTM because of their low viscosity during the process. They are very rigid materials consisting of cross-linked polymers in which the motion of polymer chains is strongly limited by the high number of existing crosslinks. During the polymerization phase, thermosetting undergoes irreversible chemical change.
The selection of a reactive thermosetting resin for RTM application forces to deal with a large number of choices of chemical engineering, mainly due to a strong relationship between the chemistry and process engineering. In fact, the process parameters, such as temperature and pressure, cannot be selected without considering the chemistry of the resin to be used. Factors to take in consideration for a RTM system can be divided into two broad categories: processing and performance. Initial viscosity and molding life are function of the temperature, and they determine the operational temperature range of a process. The molding time is a function of the rate at which the reaction occurs between the resin and the curing agent and the rate is directly proportional to the temperature. The viscosity depends on the chemical-physical characteristics of the matrix. Viscosity may change over time because of both temperature variations and as consequence of chemical reactions that occur in the liquid state. The knowledge of the rheological behavior of systems is essential for a proper setting of process parameters. In fact, the values of the viscosity during the phases of the process must be such as to guarantee both the simultaneous removal of dissolved gases and moisture entrapped in the matrix, and the compaction of the fibers, before reaching the gel point. However, the viscosity of the resin must not be too high, especially in the case in which the fiber volume fraction is higher than 40-50%.
Within thermosetting resins, several classes are suitable for aerospace applications of RTM, such as epoxy, phenolic, cyanate and bismaleimide. Phenolic resins are produced from the reaction of formaldehyde with phenol to give the condensation products. The reaction is always conducted in the presence of catalysts: these can be both acid and bases and their choice has a determinant role, together with the molar ratio of the reactants, and the nature of the reaction products. There are mainly two types of phenolic resins: resole and the novalacs. The base resins and formulated systems are available from Borden and Georgia Pacific. Approximately 91,000 tons of molded materials and phenolic are produced every year, but only a relatively small amount is used in composites for structural applications. A large number of industrial applications of phenolic resins are based on the excellent adhesive properties and strength. Especially when combined with appropriate reinforcements, phenolic resins have good chemical and thermal resistance, good dielectric strength and good dimensional stability over a wide range of temperatures. Materials produced with these resins have a very low flammability, are very resistant to creep, have low moisture absorption and have a remarkable resistance to degradation from a variety of lubricating fluids. Their low viscosity and the high char yield of these materials are used in many structures forming composite carbon/carbon. Phenolic resins are polymers that generate volatiles (mostly aqueous vapor) during the treatment phase. The volatile substances have a strong impact on the processability of these composite materials resulting in structural voids where the content can have a dramatic effect on the mechanical properties of the part. In addition, these polymers are generally brittle, characterized by a low elongation and a low tensile strength. Despite the relatively poor mechanical behavior and the difficulty of processability, these resins are becoming more applied in the structural field due to the low flammability and low smoke production. The only resins comparable to the phenolic for the properties of high fire resistance and low smoke generation are the bismaleimide resins, but they are at least an order of magnitude more expensive. The nature of the RTM process (closed molding) makes it difficult the implementation of this method due to the development of volatile substances typical of phenol in the curing phase. In order to overcome this problem clever methods have been developed. A particularly interesting approach is the use of a catalyst that allows gelation of the resin at temperatures below 100 C. So if the water is formed during the RTM process, but the temperature is maintained below the boiling point (100 C), the water will remain in the liquid phase and will act as a plasticizer. If the temperature increases above 100 C in the initial stage of gelation in the curing phase, the water will evaporate and will leave the part producing a massive degradation. A high temperature cure achieved with a ramp rather slow through the 100 C will lead the water out from the gelled structure and the cross-linking of the polymer occurs without degradation of the piece. Another issue to consider when phenolic resins are used in RTM is the acidic nature of many catalysts, which can cause corrosion in some materials for molds.
Epoxy resins are well known in the production of composite aerospace materials. The vast variety of epoxy and cure agents makes these systems very versatile in terms of manufacturing process and obtainable physical properties. Although in the last twenty years, a large innovative work in developing new formulations of epoxy resins was done, only a limited marketing of new resins was realized. When liquid epoxy resins such as DGBA and DGBF are used in RTM, they are usually part of a two-component systems. In this case the selection of the curing agent is really important. In the polyester and vinyl ester resins, the catalysts alter the cure time but do not have substantial effect on the viscosity and on the final properties of the polymer. In an epoxy system, the selection of the curing agent is crucial because it determines the thermal and mechanical properties of the matrix and defines the dependence of viscosity from the temperature, thus controlling the processability of the system. Epoxy resins polymerize with many materials such as polyamines, polyamides, phenol-formaldehyde, urea-formaldehyde, and acid anhydrides. The reactions taking place can be coupling or condensation reactions. DETDA is a liquid aromatic amine which is widely accepted as the primary hardener in many RTM formulations. DETDA is liquid at room temperature and provides good processability in RTM, both in a single-component system and bi-component one. The slow curing of epoxy system with DETDA allows these systems to be processed in a wide temperature range. The inclusion of a catalyst in the formulation of a DETDA significantly increases or decreases the reaction rate and lowers the cure temperature. The DETDA produces a polymer with high glass transition temperature (generally Tg > 177 C) when fully cured. The Young\'s modulus is usually less than 3.1 Gpa. Therefore, the use of a liquid aromatic amine such as DETDA provides an excellent processability with high glass transition temperature but with a very low value of the elastic modulus for space applications.
The aliphatic and cycloaliphatic amines are useful agents for treatment of many epoxy resins. These materials are almost all liquids with low viscosity (as DACH, IPDA, PACM, etc.) that are readily soluble in the formulation of epoxy resins. In these cases, the thermal and mechanical properties are inferior to those obtained with the aromatic amine. With these agents, the glass transition temperature is in the range 121 C – 177 C, and the elastic modulus of the polymer is in the range 2.4 GPa – 3.1 GPa. Anhydrides were widely used for many years as agents for epoxy polymerization in applications of filament winding. This class of catalysts has not received much attention in RTM applications. The liquid nature of most of the commonly used anhydrides (MTHPA, NMA, etc.) and their good solubility with the epoxy indicate that they could be used in RTM monocomponent and bicomponent systems. The availability of a large range of hardeners for epoxy-anhydride makes them available for systems that can meet specific process requirements. Generally, the formed polymers have a glass transition temperature of approximately 140 C – 150 C and a modulus of 3.45 GPa, tensile elongation of 3% – 5% and moisture absorption of 1.5%. The curing phase with an anhydride is relatively complex. The mechanism of cure can have several important consequences, such as low moisture absorption and in many cases a high final operative temperature. When anhydrides are exposed to moisture, usually over a long period of storage in a humid environment, they form acids. These acidic components interact with the basic catalysts inhibiting the polymerization, lowering the values of the modulus and the glass transition temperature, and increasing the absorption of moisture. Epoxy systems that have the greatest success in the aerospace market are the mono-component ones. There are substantial reasons for the success of these systems, such as ease of use, quality control of both process and materials and the excellent thermal and mechanical properties. In general, epoxy resins combine incomparable properties of flexibility, adhesion and chemical resistance.
The cyanate resins have a relatively small niche in the production of composites. The very high glass transition temperature and the excellent mechanical properties of the polymer are the primary guides to their use. The relatively high cost of these systems (150 – 500 U.S. $ per kilogram) prevents the entry into any market that is not closely related to their required application. This resin is generally cured with the addition of heat and transition metals as catalysts [Co(III), Cu(II), etc.]. The gelation occurs at about 50% – 60% conversion, similarly to the chemistry of an epoxy resin. The coefficient of thermal expansion is relatively small, about 50 ppm / C. Cyanate resins are often formulated with epoxy resins or maleimides in order to modify the processability and properties of the resulting polymer. Generally, the formulations include salts of transition metals and phenolic species as catalysts. There are very few formulations originally formulated for RTM. Usually cyanate resins produce a polymer with high transition temperature, low moisture absorption, good mechanical properties and excellent electrical properties. The use of them in the structures and radomes is driven by the needs of a high transition temperature coupled with a low dielectric constant and low dissipation factor to prevent degradation by high energy radiation transmitted and received through the structure. Some formulations have a flat response for both dielectric characteristics and dissipation in a wide range of temperatures and wavelengths of electromagnetic radiation. For these reasons, cyanate resins are widely used in aerospace fields. In particular, composites made by carbon fibers and cyanate resins are used in satellites for very rigid structures, with a high transition temperature and low absorption of moisture that can withstand to repeated thermal cycles without failure due to internal stresses.
Bismaleimide resins (BMI) currently provide a market niche in the manufacture of composite structures, i.e., for those parts which require a very high glass transition temperature, good stability and thermal oxidation and low flammability. The relative high cost of BMI resins (44 – 260 U.S. $ per kg) limits the applications to advanced ones. The BMI are produced by a reaction of aromatic bi-ammine precursor with maleic anhydride. The resulting resins are cured with heat and in general without additional catalysts. The unmodified BMI are fragile materials with failure strain less than 2%. In order to make these systems more resistant, modified mixtures with amines, monomers, vinyl or epoxy resins are formulated. The polymers formed in this way are reasonably resistant, but with the increasing of post-cure temperatures the fragility increases. A typical BMI resin is produced by the reaction of methylene dianiline (MDA) with maleic anhydride, using heat to remove the water produced and push the reaction to completion. A variety of process features can be obtained by changing the properties of the molecular backbone of BMI resin and adding co-reactants. The use of BMI is driven primarily by their exceptional performance at high temperatures, in particular by their ability to maintain mechanical properties at more than 149 C to below the saturation moisture. The other characteristics that lead to the use of BMI are their good electrical capacity, long term stability to the thermal oxidation for higher temperatures up to 177 C and the exceptional capacity to not generate smoke when exposed to high heat fluxes. These characteristics at high temperatures push to use these resins in the aerospace field, although at present their main application is the manufacture of electrical circuits in high temperatures. One disadvantage that seems to be common to all BMI resins is the very long time of cure. The desired properties at high temperatures are achieved only by using a high temperature post-cure. The high temperature cure and post-cure cycles lead to somewhat brittle polymers with a significant amount of residual stresses. The high temperatures of curing, accompanied by a significant shrinkage, often lead to the formation of microcracks. To minimize the problems of residual stress, slow processing rates especially during the cooling phase are used.
It is well known that the manufacturing process influences the quality and therefore the performance of the product. For instance, a good surface finish quality plays an important role in the mechanism of composite degradation upon exposure to the operative environment. The surface finish prevents the penetration of elements, such as dust, that produce and enhance micro-cracks within the structure. As consequence, a loss of mechanical properties occurs. Figure 4 shows the stages of the process that influence the behavior of the material and summarizes the relationship among process, material behavior and final performance. The compaction and impregnation phases govern the imperfections due to voids and dry spots. Following sections of this paragraph describe the compaction and impregnation phases.
Relations between manufacturing phases and material behavior.
The compaction phase is an important step that occurs in any production process for the manufacture of advanced composite structures. This phase usually takes place through the application of an external pressure, which produces a new arrangement of the fibers and changes of microstructure. In RTM, the compaction occurs when the mold is closed and the preform reaches the expected fiber volume fraction. Compaction produces large deformations and nonlinear viscoelastic effects in the preform. These effects are accompanied by a change in energy within the material. Some authors have modeled the phenomenon, introducing the function of free energy, but with limited success, because this hypothesis does not take into account permanent deformations of the preform. For instance, in case of fabric textile, when a multilayer preform is compacted, the fibers tend to be squashed with other fibers, producing interlayer packing or nesting phenomena depending on the deformation mode and the fibers architecture. If the compression load is removed, fibers tend to not return to their original position inside the preform.
Nesting is a phenomenon that produces irreversible mechanical and geometric changes of the preform modifying the permeability and mechanical properties of the composite material. In particular, the nesting influences the rigidity of the piece and even more the resistance. In particular, the stiffness depends on the positioning of the layers. If the layer is positioned out of phase without reducing the thickness (interlayer packing), there is no change of the mechanical properties. On the other hand, if two layers are in phase, i.e. in case of existing nesting, the difference of stiffness between the two configurations is reduced approximately of 10-20%. Nesting creates the so-called bridging between layers preventing delamination and increasing the resistance considerably, up to 10% for the layers out of phase. Moreover, the compaction induces residual stresses within the material due to the viscoelastic behavior of the fibers. The stress concentrations, also localized, can act as nucleation of cracks after the curing phase. However, during the impregnation phase a release of stress, probably due to the balance, occurs.
From a manufacturing point of view, it is evident that compaction changes the spatial arrangement of the fiber bundles, modifying substantially the morphology of the porosity. These variations alter the permeability of the preform and so the impregnation phase. Furthermore, compaction affects the adhesion between the layers, the material failure modes and the magnitude interlaminar shear stress more than the impregnation.
In RTM applications, the defects induced by the resin flow such as voids and dry spots are known as the biggest source of problems for production quality and reproducibility. The damage of the matrix is essentially related to the presence of porosity. The formation of micro-voids among fibers and dry spots are potential starting points for the propagation of cracks and delamination.
The resin flow front faces two resistance levels through the preform: the resistance between the fiber bundles and the resistance inside the fiber bundles. This means that the preforms are characterized by two different permeabilities: the permeability between the fiber bundles and the permeability inside the fiber bundles. These can be considered as a resin flow in macro-scale and micro-scale. The type of flow scale determines the potential void formation.
In the macro-scale, the formation of macro-voids can be formed when the air displaced from the resin remains trapped, or when pressure is insufficient to overcome the resistance of the preform or the viscosity is too high. In micro-scale, the porosity is given by micro-voids. Figure 5 shows the mechanism of void formation in the fiber bundle: the flow front runs around the tows and continues to impregnate the tow even after the passage of the front. If the air is not evacuated at the beginning of the filling process, it remains trapped in the tow and micro-voids occur at the center. Micro-voids formation can be also due to the macroscopic pressure drop. The pressure drop produces an apparent change in the permeability along the preform. The pressure drop can be explained by assuming the sink effect: the fiber bundles act as fluid sinks. The concept is based on the dual scale porous media. The individual fibers of the bundle are separated by a distance much smaller than that existing between two bundles. Consequently, the resin flows more easily between the fiber bundles rather than inside one of them. Therefore the liquid continues to impregnate the bundle even when the front part of the flow has passed. This means that a part of the injected fluid penetrates in a package of fiber, rather than push forward the front face of the flow. The result is that the pressure profile is influenced by the relative flow rate of the resin inside a bundle relative to the flow between bundles.
Mechanism of void formation in the intra-bundle.
In the RTM process, the resin flow is usually modeled with the assumption of isothermal flow, ignoring the exothermic nature of the thermosetting resin. Basing on this hypothesis, the resin flow is described by the conservation equation of mass and momentum with the boundary conditions. In order to complete the equation system, the constitutive equations of the fluid must be considered. The following section concerns the continuity and momentum equations of a resin flow within a region consisting of fibers and porosity (Figure 6).
Control volume of porous media.
The fiber reinforcement is a dual-scale porous material and to apply the conservation of momentum is an unrealistic approach. In fact, determining the pressure profile during the impregnation means to apply the Navier-Stocks equation for each channel of fibers network and solve the equation systems in their surroundings. This would allow to know the flow rate and the pressure within each channel. Anyway, a simple piece of preform may have millions of channels. This approach is impractical in a real case. Furthermore we have no interest in knowing the exact value of the pressure during the manufacturing process, but we need to know the relationship between pressure drop and flow rate during the progress of the flow front in the preform at a macroscopic level. For these reasons, the resin flow front is modeled by the Darcy law, considering that Reynolds number relative to the pore size is ≤ 1. Darcy equation (Eq. 1) describes the relationship between the flow and the pressure gradient that drives the flow through the porous medium, using the permeability parameter. This parameter, as discussed after, characterizes the fluidity of the resin through the average porosity of the fibers.
where
Rewriting Eq. 1 in expanded form:
In most RTM applications, the flow can be approximated in two-dimensional domain, since the dimensions in the plane are two or three orders of magnitude larger than the thickness. The approximation of a 3D geometry with a 2D one gives significant saves in terms of computational time and reduces the number of material parameters that need to be measured or calculated. This assumption can be considered valid since the values of permeability in the plane of the preform (in the plane in which the layers are stacked to form the thickness) are approximately of the same order of magnitude. Boundary conditions are imposed on three segments:
injection gates
free surface of the resin flow (i.e. on the flow front)
walls of the mold.
The resin is injected into the mold at constant pressure or at constant flow rate, for which the gate conditions are
or
Some injection systems allow to vary the values of pressure or flow rate during the same injection. In such case,
The pressure at the resin front flow
Inserts or multiple injection points can form several different resin flow fronts. When these fronts meet and they are not connected to a vent, the air moved by them remains trapped in the regions surrounded by the resin flow fronts. In this case, the boundary conditions on the front can be modified to consider that the pressure increases on the front due to the void pressure. The trapped air can be considered as an ideal gas for which the following relation applies:
However, this would require knowing a plot of the vacuum created during the impregnation of the fronts and calculate the volume at each instant of filling. In the real case, a part of this air is dissolved in the resin, reducing the pressure of the vacuum. In order to take into account this phenomenon, the system may include an equation of the resin diffusing at the mass-to-air interface and the diffusion coefficient has to be determined. But this is not a significant factor and researchers ignore this aspect and assume that the air will dissolve in the resin.
The boundary condition on the wall of the mold is the no-slip condition:
where
The continuity equation of resin flow through fibrous arrangement can be determined assuming that:
fibers are incompressible
variations of resin velocity and stress-strain are small in the volume control
process is quasi-steady
body forces, such as weight, are negligible.
The derivation is quite similar to that for any fluid within a region, except for the expression of the resin density
The mass balance for the volume control can be expressed as:
The term of the losses is due to an internal volume V that absorbs fluid mass in a quantity equal to (x, y, z, t) per unit volume and unit time (i.e. the fiber volume). Dividing both sides by Δx, Δy and Δz and then doing the limit for Δx, Δy and Δz 0, the mass balance becomes:
It is noted that even if the resin density
The permeability
Permeability must be determined experimentally. There are basically two methods for this: radial flow and linear flow methods. The simplest way to determine the permeability is the use of 1D version of Darcy\'s equation (linear method). For a 1D flow in the direction of the axis (assumed to be the x-axis) Darcy’s equation can be written as
Where Φ=1-Vf is the porosity of the material and Vf is the fiber volume fraction,
Integrating between the position of the injection point (
The slope of the line is calculated by plotting the position of the flow front at different times; the pressure gradient is equal to the injection pressure. In the case of orthotropic laminates, the permeability has different values in the two principal directions, and then two experiments sets must be performed.
For typical composites, the thickness is on average 2 – 3 mm. As a consequence, the transverse permeability Kz is considered negligible. This means to assume that the resin flow advances uniformly on the two external surfaces (top and bottom) and that flow velocity is an average through the thickness. However, as the thickness increases, the gradient along z (i.e. the thickness) becomes greater, due to the fact that the resin flows quickly on the upper surface, while it continues to impregnate the lower levels. Advani et al. have developed a theoretical model to calculate an average effective permeability for flat rectangular preform with thickness
where
The advantage of the numerical simulations is to help the process engineer to understand the behavior of the resin inside the mold, especially when the part geometry is complex and presents variations in permeability and fiber volume fraction. This knowledge improves the design tools and optimization of the injection scheme. General method is to use a simplified model of the resin flow reducing the problem from 3-D to 2-D and using a finite element approach and control volume (FE/CV) that does not require a re-meshing at each step. The geometry is discretized as a thin shell using triangular elements or rectangular ones. The material properties such as thickness, permeability and volume fraction of fibers can be assigned individually to each element, such as the non-uniform material properties and thickness. A linear pressure profile is assumed among the nodes of an element:
where n is the number of nodes of the element, P
where S is the stiffness matrix whose components are:
This set of equations can be solved in every moment during the filling process. The
The next step is the determination of the resin flow front progress. The approach by the control volume consists of dividing the geometry under consideration into control volumes first, and then associating one of them to each node. The flow between two control volumes is calculated by multiplying the average speed for the area connected between two control volumes. For example, the equation of the flow associated with the node i and the one associated to node j is
where s
The nodal fill factor is used to track the movement of the flow front. This factor is associated with each node and represents the fraction of the volume occupied by the control fluid. The pressures are therefore determined only at the filled nodes and empty nodes are ignored. The nodes are considered partially filled close to the flow front. The progress of the flow front is considered at any instant of time
Developing of a new composite product requires a synergy among different disciplines and sometimes entities, in other terms a Concurrent Engineering (CE) approach. This section shows some aerospace components manufactured by RTM process in CE method. The prototypes presented in the following sections are the results of years of collaboration between the School of Aerospace Engineering (currently DIAEE) of Sapienza University of Rome and Italian aerospace industries (AgustaWestland and Aermacchi).
The need of high quality production, due to market pressure and high-tech demands of the aerospace field, drives to the faster and most effective design of the product. To this aim, engineers adopt new methods based on concurrent approaches to optimize the part before manufacturing the final piece. Especially from 1990s, with the explosion of the composite materials market in several industrial fields, involved people from industry and universities are working to determine the best way to apply the concurrent engineering as a systematic approach for product development. Some works are addressed to improve the management team and communication among members; others go toward building a virtual environment based on CAD systems.
The software systems for automation design tools are powerful. They can help any company to develop products of superior quality, faster and at lower cost. This implies clear advantages in terms of competitiveness. The empirical methods "test and fix" still dominate the field of molding technologies for composite materials, but this approach produces deleterious effects in terms of cost and time. Simulation studies lead to the complete optimization of the product before creating the prototype. The objective is to establish the optimal characteristics of the preform and tooling, optimizing the process parameters.
The targets that can be obtained with the use of a code are:
reduction of design time
reduction of the costs and consumption of materials
optimization of the design parameters in relation to the process
reduction of the times of modification and tuning of the molds
integration between production process and optimization of the component with respect to constraint and loading given by specification.
About the entities involved in a project, concurrent-development teams typically exhibit the following characteristics:
they include no more ten members
members choose to serve on the team
members serve from the beginning to the end of the project
members participate in the team fulltime
members report solely to the team leader and the leader reports to general management
key functions - at least marketing, engineering, and manufacturing - are included in the team
members are co-located within conversational distance of each other
The plan should give specific information about the qualification programs regarding all the entities involved in the RTM process: materials, process, tooling, tests.
Figure 7 shows the flowchart related to the CE approach set by the DIAEE of Sapienza University of Rome during the development of several RTM helicopter components. The flowchart highlights the structural and manufacturing couplings. Process parameters have been considered at the early stage of the design as a discrimination of the material selection. The resin flow behavior and the filling time of the mold were the process criteria. These parameters are directly dependent on the preform characteristics such as the textile structure, the laminate orientation and the fiber volume fraction. The preform characteristics are the first features that determine the mechanical performance of the component. In this sense, the optimized project is a compromise between structural and process optimizations and requires a concurrent engineering design and manufacturing.
The strake is a typical aerodynamic surface used in both supersonic and subsonic vehicles to improve the stability and/or reduce the drag. The thickness of the structure is around 2-3 mm and usually made in aluminum alloy. In this case, the selected resin was a mono-component benzoxazine polymer (Henkel Epsilon 99110). The recommended process conditions were typical infusion temperature at 90 °C and curing at 180 °C for 90 min. The fiber reinforcement used was a carbon textile HEXCEL G0926 5H Satin. The preforms were realized manually overlaying several layers adopting a predefined lamination sequences. The lamination sequences were determined by structural analysis. The injection equipment was a commercial Hyperject machine for mono-component polymers. The Hyperject injects the resin at constant pressure and it is provided with heated dispending resin. The resin was loaded, degassed and heated inside the Hyperject. When both the temperatures of the resin and the mold were reached, the resin was pumped inside the mold until the resin came out from the vent. Molds were studied to be multi-components in order to make easily the demolding.
Flowchart of concurrent design and manufacturing
The numerical analysis was performed by commercial codes based on a finite element analysis-control volume (FEM-CV). Modelling of the flow was to allow investigating the resin impregnation process and strategically designing gates and vents and injection scheme in order to optimally fill the composite part without any dry spot. The analysis took into account the most relevant process parameters such as injection pressure and material features like the resin viscosity and permeability of the preform. The FEM-CV analysis was isothermal and provided detailed information about the pressure field, flow front patterns, and strategic injection scheme. The different choice of gate positions affects very much the filling time and the quality of the finished part. For these reasons, different injection schemes were considered. All simulations were performed using the resin viscosity value at the mold temperature.
Figure 8 shows the simulation result of the best injection scheme. In particular, the simulation represents the trend of the filling time. Figure 9 shows the prototype of the strake after demolding.
Injection scheme of the mold as determined by numerical simulation. On the top: filling time trend through the preform. On the bottom at left: carbon fiber reinforcement before closing mold.
Strake of Aermacchi nacelles after demolding.
The aim of the work was to realize a primary structure of a helicopter by RTM process in order to compare its properties with those of the parts made with classical hand lay-up technique. The chosen component was the inboard flaperon of the BA609 (Bell Agusta), which is an aerodynamic control surface that presents different critical features. In fact, the inboard flaperon is a primary component so the reliability must be nearly absolute. Further, it is a large part and involved a complicated lamination sequence that can affect the manufacturing process. It is evident in Figure 10 the presence of three different lamination sequences that correspond to different permeability, which was determined experimentally.
Finite element model of the inboard flaperon with a particular on a rib (red component on the right). The different colors individuate the different permeability values associated to the lamination sequence.
In the first scheme, the injection points were placed on the two leading edge borders of the skin in correspondence of the rib reinforces and the venting points on the trailing edge line. As shown in Figure 11, the total filling time given by this configuration is very long (more than 1.5 h) and comparable with the resin pot life limit.
A second scheme has been analyzed. In this case five injection points were placed in the middle of each skin side and between the rib reinforces. The venting points were located both on the trailing and leading edge lines. With this second scheme the filling time was considerably reduced down to 20 min in good agreement with the resin processability. From the results of the previous simulation it was noted that much time was needed to fill a very small area near the outbord side. For this reason a further optimization was carried out including a sixth injection point in this area. With this simple modification the total filling resulted to be less than half of the previous simulation (Figure 12).
Filling time with the first injection scheme and predicted resin flow rate during the injection with the first scheme.
Filling time trend for the injection scheme selected for the mold.
The dry fabric plies for the construction of the preform were cut with the GFM ultrasonic cutting machine using a multilayer method. In this way some areas of the preform were cut directly in the final lamination sequence allowing for considerable time saving in the preform assembly phase. The different plies and sequences were sticked together on a flat surface using an adequate agent (binder). It was used the same cut program and operative cycle of the original part. In Figure 13, the glass layers used to replace the syntactic foam can be seen. The use of the glass mat strongly improves the permeability of the preform allowing very much shorter injection times. Further, the syntactic foam was incompatible with the RTM process.
Particular of preform preparation. On the right: glass layers used to replace the syntactic foam of the original component.
On the top: moment of the impregnation phase. On the bottom: the final component after demolding.
The bracket is a secondary element that is present in large numbers in a helicopter. Usually it is made by metal alloy. The aim to re-design the bracket in composite materials is to reduce the weight and time of production. In this case, a consistent saving can be reached adopting an automatic textile process, which avoids the long time due to the lamination. The stitching was the selected preform technique. Figure 15 shows the cut of the layers and the preform after the assembling. Figure 16 shows the realization of the component during the impregnation phase and the part demoded after the curing step. In this case, the use of RTM process permits to save 30% weight with respect to its equivalent in metal alloy and reduces drastically the production cycle.
Realization of the preform: cut and stitching.
Realization of the bracket by RTM process: resin injection (left), bracket demolded (right).
One of the major objectives of modern biology and medicine is prediction: being able to take information about an individual’s genome and environment and accurately predict their phenotype. This effort has taken on many forms and many names in different fields over time including population genetics [1], statistical genetics, quantitative genetics [2], genetical genomics [3], complex trait analysis [4], systems genetics [5, 6], systems medicine [7, 8], personalized medicine [9], predictive medicine and precision medicine [10, 11]. In humans, this has been greatly constrained by the
How then, if there is so much complication in this one-to-one relationship (one gene variant to one phenotype), can we uncover the true many-to-many-to-many relationships that occur in biology? Phenotypes at many levels, including behavior, organ systems, cells, proteins, metabolites, and mRNAs, all interact together with sets of many gene variants, and with an individual’s current and previous environmental exposures. We need to understand gene–gene (epistasis), gene-age, gene-sex, gene-treatment, and gene–environment interactions and all their combinations. One answer to this is through the use of recombinant inbred (RI) populations and their derivatives.
Recombinant inbred (RI) populations are a seemingly simple idea: two inbred strains are crossed, and their F1 progeny are then crossed again to produce an F2. Pairs of these F2 animals are mated, and new lines are established through repeated rounds of sib-mating (Figure 1A). By generation F20, we have a population of 99% inbred strains, each of which is a unique mosaic of homozygous genetic regions from both the parents, and for which an effectively infinite set of genetically identical individuals can be produced [24, 25]. This combination of genetic variability between strains but identical genome within strains allows the mapping of linkage between genotype and phenotype. The design has been expanded on in a variety of ways [26], such as increasing the number of parental strains (e.g. the 8 founders used for the Collaborative Cross mice [27, 28]) to increase the number of variants that segregates in the population, or using multiple rounds of crossing before inbreeding, producing so-called Advanced Intercross RI strains (AI-RI) to increase the number of recombinations, and therefore the precision of mapping (Figure 1B; [29]). Although RI strains were first developed in mice, and it is mice that we will concentrate on in this chapter, the design has now been used for a wide variety of organisms, including
Production of the BXD family, transgenic crosses, and diallel crosses. Approximately half of the BXD strains are from an F2 (A; epochs 1, 2, 4 and 6), and approximately half of the BXD strains are from advanced intercrosses (AI; B; epochs 3 and 5). Red represents regions of the genome coming from C57BL/6 J (B6), and white represents regions from the DBA/2 J (D2). Solid arrows have been used to represent a single generation of breeding. Trangenic and non-transgenic crosses for QTL mapping can be produced by crossing hemizygous transgenic mice to RI individuals, to produce litters containing both genotypes (C). The transgene is represented in yellow. A diallel cross (DAX) includes all combinations of genotypes, including the inbred ‘diagonal’, and all reciprical crosses (D). All offspring of the DAX are isogenic, meaning that genotypes are replicable.
These RI families are an essential complement to data collected in humans, allowing us to build experimental platforms for what is now called precision medicine. Each isogenic RI strain within a family is effectively an immortal genome-type. This is important because it allows the same genome to be resampled using any tissue, at any age, with any method, with any environmental exposure or treatment that the researcher cares to use. This allows us to model higher-order genome-environment interactions: the many-to-many-to-many problem stated above.
Whereas in human cohorts we have to imagine a counterfactual (e.g. what would have happened had I exercised more?), in isogenic strains we can effectively run this counterfactual – almost perfectly genomically and environmentally matched individuals can be phenotyped with only a single environmental perturbation between them. Even better, we can have multiple duplicates of these identical genome-types within each arm of the study, allowing us to reduce the effect of unwanted environmental perturbations, increasing our power to detect true associations [38]. However, in some sense, this is still an
The goal is accurate genome-phenome prediction. With this goal in mind, we will use the BXD family of isogenic mouse strains as our example of how this can be achieved. The BXDs are by a wide margin the largest and most deeply phenotyped mammalian family and can be used as a testbed for experimental precision medicine.
The BXD family were among the first RI strains to be produced [24, 42, 43]. This work was started by Benjamin A. Taylor who crossed female C57BL/6 J (B6 or B) and male DBA/2 J (D2 or D) strains—hence BXD (Figure 1A). The first sets of BXDs were intended for mapping Mendelian loci [42, 44], but the family was also used to map complex traits such as cancer and cardiovascular disease [45, 46, 47, 48], variation in CNS structure [49, 50, 51, 52], and behavioral and pharmacological differences [53, 54, 55, 56, 57, 58, 59, 60, 61, 62]. Twenty-seven of the original 32 BXD strains are still available from The Jackson Laboratory (JAX). In the mid-1990s, Taylor began the production of a second set of BXDs [44] and added nine new strains (BXD33–BXD42). BXD1-BXD42 carry the strain suffix “/TyJ”.
We started production of another wave of BXDs at UTHSC in the late 1990s [29]. These new lines were derived from advanced intercross (AI) progeny that had accumulated chromosomal recombination events across 8 to 14 generations [63] (Figure 1B). These AI-derived BXDs incorporate roughly twice as many recombinations between parental genomes than do conventional F2-derived BXDs [63, 64, 65, 66, 67]. This improves mapping precision nearly two-fold. BXD strains BXD43 and above from UTHSC were donated to JAX once fully inbred, and carry the strain suffix “/RwwJ”.
The BXD family has been used to define specific genes and even sequence variants corresponding to 20 or more QTLs. These include two tightly linked genes,
Two things now set the BXD family apart from all other recombinant inbred populations: the number of strains within the family, and the deep, coherent phenome that has been collected for them.
The BXD family is the largest mammalian recombinant inbred population, having expanded during its lifetime, from ~20 [42], to ~35 [44], to ~80 [29], to a total of 198 strains with data on GeneNetwork.org. There are 123 BXD strains currently distributed by The Jackson Laboratory (JAX) and an additional seventeen strains available at UTHSC, soon to be donated to JAX [82]. All 140 of these strains are available under a standard material transfer agreement. This expanded number of easily accessible strains increases the power and precision of linkage studies [82].
As the number of strains increases, there is an increase in the number of recombination junctions within the population, and consequently, quantitative trait loci (QTLs) can be narrowed down to smaller intervals. This is improved still further by the fact that approximately half of the BXD family are derived from advanced intercrosses, each of which will have a larger number of recombinations than their F2 derived cousins. We have demonstrated that when using approximately half of the family (60–80 strains), precision is close to 1 Mb for many traits [82]. This is also partially due to two other features of the family. The first, common to all RIs, is that the effective heritability of the trait can be boosted by resampling the same genome-type [38], and the second, that because there are two parents in the population, there is a well-balanced distribution of the two haplotypes across the genome (the mean minor allele frequency is ~0.44).
When carrying out QTL mapping the largest gain of power is given by increasing the number of genome-types tested [38, 73], and therefore, as the largest RI family, the BXD have the most power to detect genotype–phenotype linkage. A simple app has been produced to estimate power to detect QTL in the BXD, available at http://power.genenetwork.org [82]. When we examine power in the BXD family, we see a fact that might seem counter-intuitive to some: power is always increased more by increasing the number of strains compared to increasing the number of within strain biological replicates, even when heritability is low. Even at low-to-moderate heritabilities, increasing replicates above 6 within-strain gives very little improvement in power.
We should also note that the effect sizes seen in the BXD family (and other two-parent RIs), appear to be high, but this is correct, as effect size is highly dependent upon the population being studied. Effect sizes measured in families of inbred lines are typically much higher than those measured in an otherwise matched analysis of intercrosses, heterogeneous stock, or diversity outbred stock. Two factors contribute to the higher level of explained variance of loci when using inbred panels. The first reason is due to replicability. When effect size is treated as the proportion of total genomic variance explained by the QTL, effect size will increase as environmental effects decrease due to replication. That is, resampling decreases the standard error of the mean, suppressing environmental “noise” [38]. This is in addition to the increase in heritability above (i.e. an increase in total variance explained by the total genomic variance).
The second reason is that nearly all loci in inbred panels are homozygous and the same number of sampled animals will account for twice as much genetic variance as in an F2 cross, and four times as much variance as in a backcross [38]. When phenotyping with fully homozygous strains we are only examining the extreme ends of the distribution, providing a boost in power to detect additive effects. The downside is obvious: we cannot detect non-additive effects. However, if we add in members of the diallel cross population (DAX), we can now estimate both dominance and parent-of-origin effects. This is a topic we will come to later.
As well as being the largest recombinant inbred family, the BXD are also the most deeply phenotyped. Over 40 years of data is now openly and publicly available at genenetwork.org, providing an unrivaled resource. This dense and well-integrated phenome consists of over 10,000 classical phenotypes [83]. The phenome begins with Taylor’s 1973 analysis of cadmium toxicity, through to recent quantitative studies of addiction [84, 85, 86], behavior [87, 88, 89, 90], vision [91], infectious disease [92, 93, 94], epigenetics [95, 96], and even indirect genetic effects [97, 98, 99]. The BXDs have been used to test specific developmental and evolutionary hypotheses [49, 100, 101]. They have allowed the study of gene-by-environmental interactions, with environmental exposures including alcohol and drugs of abuse [86, 102, 103, 104, 105], infectious agents [71, 106, 107, 108, 109], dietary modifications [110, 111, 112, 113, 114, 115], and stress [116, 117]. The consequences of interventions and treatments as a function of genome, diet, age, and sex have been quantified [90, 96, 115, 118, 119, 120], and gene pleiotropy has been identified [121].
Beyond this, there is now extensive omics data for the BXD. Both parents have been fully sequenced [75, 122, 123], and deep linked-read and long-read sequencing of 152 members the BXD family is underway. Over 100 transcriptome datasets are available (e.g, [124, 125]), as well as more recent miRNA [84, 126], proteome [118, 120, 127], metabolome [75, 118, 125], epigenome [95, 128], and metagenome [93, 129] profiles. Nevertheless, much more is still to be done, as many of these measures have only been taken in the liver or in specific brain regions [118, 120]. However, as each of these new datasets is added, they will be fully coherent with previous datasets, multiplicatively increasing the usefulness of the whole phenome.
Access to this plethora of data is freely available from open-source web services, allowing users to download the data, or to make use of powerful statistical tools designed for global analyses that are integrated into websites (e.g. GeneNetwork.org, bxd.vital-it.ch, and Systems-Genetics.org) [125, 130, 131].
It cannot be overstated how important it is that those using the BXDs gain access to coherent genomes and quantitative phenomes generated under diverse laboratory and environmental conditions [83, 132]. New data can be compared to thousands of publicly available quantitative traits, and with each addition, the number of network connections grows quadratically—enabling powerful multi-systems analysis for all users [73, 111, 112, 118, 125, 133]. Causal pathways can be produced from genome variants, to gene expression, to metabolite levels, to phenotype [73]. Within minutes of finding a gene of interest, a researcher can look for correlations between its expression and thousands of other genes, across dozens of tissues. Enrichment analysis can then be carried out on these ‘gene-friends’ suggesting pathways and networks that your gene of interest may be associated with. Correlations can be found between the expression of your gene and over 10,000 phenotypes, giving suggestions of the role of the gene at the whole-organism level. Shared QTLs, where both the gene-expression and a phenotype of interest are associated with the same locus, provide strong evidence of a genetic link. Using GeneNetwork.org we can build biological networks, moving from genetic variant, to expression difference, to protein expression, to whole-system outcomes, with just a few keystrokes, and without touching a lab bench [134, 135, 136]. Entire manuscripts can be written without leaving a web browser [137]. This is a massive step forward that is under-appreciated by many.
The above demonstrates how the BXD can help us achieve our goal of predictive modeling of disease risk and the efficacy of interventions [138]. Indeed, the family has already been used to test specific functional predictions of behavior based on neuroanatomical variation [139]. The BXD family is well placed to address these questions that encompass both high levels of genetic variation and gene-environmental interactions: our many-to-many-to-many problem. This is bolstered by the family’s easy extendibility into a massive diallel cross population (DAX).
The diallel cross is another simple idea that has been with us for over 60 years [140, 141, 142]. We now have the major opportunity to take full advantage of this approach using large panels of fully sequenced isogenic strains. A DAX is the set of all possible matings between several genome-types (Figure 1D). For the C57BL/6 J and DBA/2 J there are the two reciprocal F1s, and these have been used to study parent-of-origin effects and to estimate heritability (e.g. [53]). As the number of parental strains increases, the number of potential diallel crosses increases exponentially, and tools have been developed to deal with large DAXs [143]. Although we have learnt much about the genetic architecture of traits [53, 143, 144, 145, 146, 147], QTL mapping has been more difficult, given the relatively small number of strains used [148]. We can now imagine the full DAX for the BXD family of 140 strains – 19,460 replicable isogenic F1s, all of which have a reproducible, entirely defined genome, and any subset of which can be generated efficiently for
At the first level, this has important consequences for power and precision. The number of strains phenotyped can be increased massively, giving power to detect loci with even the weakest of effect sizes [148]. Precision can also be enhanced, as F1s can be produced which segregate for a narrow region of the genome, producing a small QTL interval containing fewer genes. All the data collected in these F1s can be coherently integrated into the phenome already aggregated for the BXD, meaning that every new phenotype measured adds quadratically to the phenome and that any user of this F1 has access to over 40 years of data.
At the next level up, it also allows us to detect, for example, dominance and parent-of-origin effects mentioned above. Small DAXs of mouse strains have been able to identify parent-of-origin effects, epistasis, and dominance, but have been unable to map the loci causing these effects [53, 143, 144, 145, 146, 149, 150]. By using reciprocal crosses of inbred strains (e.g. BXD001xBXD002F1 vs. BXD002xBXD001F1), we can produce isogenic litters, the members of which are all genetically identical, and whose only differences are due to parent-of-origin effects [151] (Figure 1C). By building a large DAX of reciprocal crosses, the genomic loci causing these dominance, epistatic, and/or parent-of-origin effects can be identified. Mapping of these non-additive effects is a complete dark zone in fully homozygous inbred populations.
Finally, and most importantly, the DAX provides a population for the testing of predictions. Using the BXD family we have enough strains to make associations, whether gene-phenotype, environment-phenotype, or gene–environment-phenotype, with high power. However, using only the inbred BXD lines, we do not have a second population in which to test predicted associations. The BXD DAX provides a matrix of 19,600 isogenic genome-types. If only the ‘diagonal’ of inbred BXD strains are used to detect associations and make predictions, any of the 19,460 isogenic F1s are available to test these associations and predictions (Figure 1D).
We can expand the DAX even further using easily available isogenic strains. There are approximately 200 RI strains from other two-parent mouse populations, including AXB/BXA (29 strains), AKXD (20), BXH (11), BRX58N (7), CXB (19), ILSXISS (60), LGXSM (~18), NXSM (16) and SWXJ (12), plus approximately 55–75 strains from the Collaborative Cross 8-parent RI population [28]. From these inbred parents, there are over 152,100 isogenic F1s that can be produced and replicated. An additional expansion of this design is to cross RI families to genetically engineered disease models.
Genetically modified animals, including humanized, transgenic and knockout mouse models, have been a vital piece in uncovering genotype–phenotype associations, but they have often suffered from the same
An excellent example of this already exists: the Alzheimer’s disease BXD (AD-BXD) panel developed by Kaczorowski and colleagues [175, 176]. By crossing C57BL/6J-congenic females hemizygous for the humanized 5xFAD transgene (JAX Stock No. 008730) to males from BXD strains, they produced litters, half of which had the 5xFAD transgene (the AD-BXD), and half of which did not have the 5xFAD transgene (non-transgenic-BXD). The whole litter is genetically and environmentally identical except for the presence of the transgene, giving an immediate and directly comparable control (Figure 1C). By crossing the humanized 5xFAD line on a single genetic background to a diverse but defined set of BXDs, they produced a population that incorporates high levels of sequence variation mirroring that of humans. They have mapped genetic and molecular causes of cognitive loss in AD-BXD mice [154, 175, 176, 177, 178, 179], including a broad spectrum of cognitive loss similar to that of humans with familial and late-onset AD [177]. The human transgenes in the 5XFAD line [180] sensitizes BXD hybrids to a greater or lesser degree—some begin to lose conditioned fear memory as early as 6 months; others well after a year [175], demonstrating a gene-by-gene-by-age interaction. Variation is highly heritable and mappable and gives a powerful means by which to define genetic causality and mechanisms of memory and non-cognitive loss and resilience to loss.
Neuner et al., were also able to demonstrate ‘reverse translation’ from human genomic data to mouse phenotype [175]. They generated a polygenic genetic risk score using 21 human genes which increase Alzheimer’s disease risk, and showed that the allele dosage was significantly associated with cognitive outcomes in the AD-BXD. This confirms firstly, that naturally occurring variation in these networks has overlapping effects in mice and humans, and secondly that gene-phenotype associations translate across species. This approach can be applied to many other phenotypes.
Given that phenotypes from genetically engineered mice on a single genetic background cannot be reliably generalized to other mouse genetic backgrounds [158], it is unsurprising that there are difficulties in generalizing to other species. By crossing genetically modified lines to RI strains to produce a DAX, we overcome this problem and allow the integration and translation of data to other populations and other species.
Compared to conventional F2s and advanced intercrosses (AIs), outcrossed heterogenous stock, or diversity outbred stock, the BXD are particularly advantageous when the heritability of a trait is moderate or low because the genetic signal can be boosted greatly by resampling isogenic members of the same line many times [38]. The drawbacks of the BXDs are lower precision, and a decreased amount of variation in the population compared to e.g. multiparent families (such as the Collaborative Cross and the Diversity Outbred), and a consequent decrease in the total phenotypic variance [181]. We consider this an acceptable drawback, as we have shown that medically relevant phenotypes have variation in the family and it is possible to achieve subcentimorgan mapping precision using only half of the full set of strains [82]. Beyond this level of precision, an efficient method to transition from QTLs to causal genes, variants, and mechanisms is to take advantage of complementary resources. These include sets of other murine mapping resources, efficient
As a specific example of combining murine populations, Taylor’s cadmium testicular toxicity mutation (BXD Phenotype 13035) that was unmappable in 1973 now maps to 3 Mb on GeneNetwork.org. When combined with SNP data for common strains, the variant can be restricted to a 400 Kb region that includes the causal
Mouse-to-human genetic translation has at least a 20-year history [184], but has taken off now that GWAS are routine [48, 78, 111, 112, 123, 125, 185, 186]. Human GWAS data can be used to refine QTL found in mice, e.g. taking advantage of the power to detect associations in the BXD to identify a homologous region in humans, and then using the precision of human GWAS to identify a candidate gene [185, 186, 187].
More importantly, mouse data can be used to determine the function and causal pathway for associations made in humans. Finding variant-phenotype associations for any phenotype with GWASs is now only limited by one’s ability to collect phenotypes, but interpreting and determining the function of these variants is far more difficult, given the environmental and genetic variation in any human population. RI mice, such as the BXD, provide a method of ‘reverse-translation’, from human-to-mouse. Again, the work of Kaczorowski and colleagues above provides an excellent example [175] that can be applied to any other phenotypes.
Despite occasional arguments to the contrary [188, 189], mice, when used correctly, are a good model of human biology and medicine [12, 190, 191, 192]. Indeed, at least 40 Nobel Prizes have been awarded for research involving mice (http://www.animalresearch.info/en/medical-advances/nobel-prizes) [193], and their use has been vital in understanding the pathogenesis of many diseases. For true predictive medicine, we need to understand all gene-by-gene-by-environment-by-age-by-sex-by-treatment interactions [160], and animal models are the only way to do this at scale. The importance of using genetically diverse mice has often been overlooked, leading to difficulties with translation. RI families, such as the BXDs, and their expansions [130], including diallel crosses and reduced complexity crosses [194, 195], overcome this problem and are a vital step towards accurate, individualized, predictive medicine.
The UTHSC Center for Integrative and Translational Genomics (CITG) has supported production of the BXD colony at UTHSC and will continue to support this colony for the duration of the grant. The CITG also provides generous support for computer hardware and programming associated with GeneNetwork, and our Galaxy and UCSC Genome Browser instances. We thank the support of CITG, and funds from the UT-ORNL Governor’s Chair, NIDA grant P30 DA044223, NIAAA U01 AA013499 and U01 AA016662, NHLBI R01 HL151438, and NIDDK R01 DK120567 for the work at UTHSC.
The authors have no conflicts of interest.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Transmission electron microscopy (TEM) is the starting point for obtaining the best resolution of images. Two different techniques are available and described in this paper. Firstly, negative staining of viral suspensions provides detailed information of virus particles' structure. It is a technique that can be quickly performed and is able to accommodate the highest magnifications of virus particles. Secondly, ultra-thin sections of virus-infected tissues or cell cultures, combined with a positive staining technique can provide information regarding the localization of viruses inside or around cells. 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Lentil crops are vulnerable to a number of diseases caused by fungi, viruses, nematodes, insect pests, parasitic plants and abiotic stresses. Among them, the most significant and serious soil-borne disease is Fusarium wilt (Fusarium oxysporum f.sp. lentis: Fol). Fusarium wilt causes yield loss up to 50% in farmers’ fields. The pathogen showed high levels of phenotypic and genotypic diversity in India, Algeria, Syria and Iran. The disease thrives at 22–25°C temperature and affect lentil either at seedling and vegetative or the reproductive stages of the crop. To minimize yield losses, an integrated management strategy comprising resistant/partial resistant cultivars, adjusting sowing time, bio-control and chemical seed treatments is the best approach to reduce the incidence of the Fusarium wilt of lentil. This review covers past achievements in managing the disease, pathogen diversity and identify gaps in managing Fusarium wilt to improve productivity and production of the crop.",book:{id:"6329",slug:"fusarium-plant-diseases-pathogen-diversity-genetic-diversity-resistance-and-molecular-markers",title:"Fusarium",fullTitle:"Fusarium - Plant Diseases, Pathogen Diversity, Genetic Diversity, Resistance and Molecular Markers"},signatures:"Neha Tiwari, Seid Ahmed, Shiv Kumar and Ashutosh Sarker",authors:[{id:"213094",title:"Dr.",name:"Neha",middleName:null,surname:"Tiwari",slug:"neha-tiwari",fullName:"Neha Tiwari"},{id:"213095",title:"Dr.",name:"Ashutosh",middleName:null,surname:"Sarker",slug:"ashutosh-sarker",fullName:"Ashutosh Sarker"},{id:"213176",title:"Dr.",name:"Seid Ahmed",middleName:null,surname:"Kemal",slug:"seid-ahmed-kemal",fullName:"Seid Ahmed Kemal"}]}],onlineFirstChaptersFilter:{topicId:"407",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:36,paginationItems:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}}]},overviewPagePublishedBooks:{paginationCount:32,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"213786",title:"Dr.",name:"Henrique P.",middleName:null,surname:"Neiva",slug:"henrique-p.-neiva",fullName:"Henrique P. 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