Results of the drying of the granular materials in the shelf dryer.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"4762",leadTitle:null,fullTitle:"Recent Advances in Thermo and Fluid Dynamics",title:"Recent Advances in Thermo and Fluid Dynamics",subtitle:null,reviewType:"peer-reviewed",abstract:"Thermodynamics is a branch of physics concerned with heat and temperature and their relation to energy and work. It defines macroscopic variables, such as internal energy, entropy, and pressure, that partly describe a body of matter or radiation. It states that the behavior of these variables is subject to general constraints that are common to all materials, not to the peculiar properties of particular materials. These general constraints are expressed in the three laws of thermodynamics which had a deep influence on the development of physics and chemistry. The book aims to present novel ideas that are crossing traditional disciplinary boundaries and introducing a wide spectrum of viewpoints and approaches in applied thermodynamics of the third millennium. The book will be of interest to those working in the fields of propulsion systems, power generation systems, chemical industry, quantum systems, refrigeration, fluid flow, combustion, and other phenomena.",isbn:null,printIsbn:"978-953-51-2239-5",pdfIsbn:"978-953-51-6650-4",doi:"10.5772/59835",price:139,priceEur:155,priceUsd:179,slug:"recent-advances-in-thermo-and-fluid-dynamics",numberOfPages:342,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"97b61cacac0ee85c33d374055e498d2a",bookSignature:"Mofid Gorji-Bandpy",publishedDate:"December 21st 2015",coverURL:"https://cdn.intechopen.com/books/images_new/4762.jpg",numberOfDownloads:19557,numberOfWosCitations:8,numberOfCrossrefCitations:8,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:13,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:29,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 12th 2014",dateEndSecondStepPublish:"December 3rd 2014",dateEndThirdStepPublish:"March 9th 2015",dateEndFourthStepPublish:"June 7th 2015",dateEndFifthStepPublish:"July 7th 2015",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy",profilePictureURL:"https://mts.intechopen.com/storage/users/35542/images/system/35542.jpg",biography:"Dr. Mofid Gorji-Bandpy received his MS in Mechanical Engineering from the Faculty of Engineering, University of Tehran, Iran, in 1978. In 1990, he obtained his Ph.D. in Hydraulic Engineering from the School of Engineering, University of Wales College of Cardiff (UWCC), UK. At present, he is a full professor in the Department of Mechanical Engineering at the Babol Noshirvani University of Technology, Babol, Iran. He is also a visiting professor in the Department of Mechanical and Industrial Engineering at the University of Toronto, Canada. His major interests are in advanced methods of energy-conversion systems, turbo machinery, fluid mechanics, water distribution networks, and solutions to both energy and environmental problems. He has published more than 300 papers in these fields. He has also published several refereed publications in different fields of mechanical engineering, applied mathematics, and aerodynamics. In addition, Dr. Gorji-Bandpy was recognized as a Highly Cited Researcher by Clarivate Analytics in 2017 and 2018.",institutionString:"Babol Noshirvani University of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Babol Noshirvani University of Technology",institutionURL:null,country:{name:"Iran"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"704",title:"Thermal Engineering",slug:"engineering-chemical-engineering-thermal-engineering"}],chapters:[{id:"49000",title:"Prediction of Solubility of Active Pharmaceutical Ingredients in Single Solvents and Their Mixtures — Solvent Screening",doi:"10.5772/60982",slug:"prediction-of-solubility-of-active-pharmaceutical-ingredients-in-single-solvents-and-their-mixtures-",totalDownloads:2424,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this chapter, the applicability of two predictive activity coefficient-based models will be examined. The experimental data from five different types of VLE (vapor-liquid equilibrium) and VLLE (vapor-liquid-liquid equilibrium) systems that are common in industry are used for the evaluation. The nonrandom two-liquid segment activity coefficient (NRTL-SAC) and universal functional activity coefficient (UNIFAC) were selected to model the systems. The various thermodynamic relations existing in the open literature will be discussed and used to predict the solubility of active pharmaceutical ingredients and other small organic molecules in a single or a mixture of solvents. Equations of states, the activity coefficient, and predictive models will be discussed and used for this purpose. We shall also present some of our results on solvent screening using a single and a mixture of solvents.",signatures:"Ehsan Sheikholeslamzadeh and Sohrab Rohani",downloadPdfUrl:"/chapter/pdf-download/49000",previewPdfUrl:"/chapter/pdf-preview/49000",authors:[{id:"175235",title:"Dr.",name:"Sohrab",surname:"Rohani",slug:"sohrab-rohani",fullName:"Sohrab Rohani"}],corrections:null},{id:"49548",title:"Dynamics of Droplets",doi:"10.5772/61901",slug:"dynamics-of-droplets",totalDownloads:1896,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Capturing non-Newtonian power-law drops by horizontal thin fibers with circular crosssection in a quiescent media can be studied in this chapter. The case is simulated using volume of fluid (VOF) method providing a notable reduction of a computational cost. Open source OpenFOAM software is applied to conduct the simulations. This model is an extension of the one developed earlier by Lorenceau, Clanet, and Quéré [1]. To validate the model, water drops affecting a fiber of radius 350μm were simulated and threshold drop radiuses were obtained regarding to the impact velocity. These results agreed well with the experimental data presented by Lorenceau et al. [1]. In the next step, non-Newtonian power-law drops landing on thin fiber of radius 350μm were simulated. The final goal of this study was to obtain the threshold velocity and radius of a drop that is completely captured by the fiber. Threshold radiuses for both shear-thinning and shear-thickening drops were obtained and compared with corresponding Newtonian drops. Results show that the threshold radius of drop increases in a fixed velocity as n, power-law index, increases. Furthermore, shear-thinning nature of the drop leads to instabilities in high Reynolds numbers (Re) as it influences the fiber.",signatures:"Hossein Yahyazadeh and Mofid Gorji-Bandpy",downloadPdfUrl:"/chapter/pdf-download/49548",previewPdfUrl:"/chapter/pdf-preview/49548",authors:[{id:"35542",title:"Prof.",name:"Mofid",surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"},{id:"179045",title:"MSc.",name:"Hossein",surname:"Yahyazadeh",slug:"hossein-yahyazadeh",fullName:"Hossein Yahyazadeh"}],corrections:null},{id:"48989",title:"Nonequilibrium Thermodynamic and Quantum Model of a Damped Oscillator",doi:"10.5772/61010",slug:"nonequilibrium-thermodynamic-and-quantum-model-of-a-damped-oscillator",totalDownloads:1694,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"We describe the linearly damped harmonic quantum oscillator in Heisenberg’s interpretation by Onsager’s thermodynamic equations. Ehrenfest’s theorem is also discussed in this framework. We have also shown that the quantum mechanics of the dissipative processes exponentially decay to classical statistical theory.",signatures:"Gyula Vincze and Andras Szasz",downloadPdfUrl:"/chapter/pdf-download/48989",previewPdfUrl:"/chapter/pdf-preview/48989",authors:[{id:"54033",title:"Dr.",name:"Gyula",surname:"Vincze",slug:"gyula-vincze",fullName:"Gyula Vincze"},{id:"141192",title:"Prof.",name:"Andras",surname:"Szasz",slug:"andras-szasz",fullName:"Andras Szasz"}],corrections:null},{id:"49204",title:"Linear Approximation of Efficiency for Similar Non- Endoreversible Cycles to the Carnot Cycle",doi:"10.5772/61011",slug:"linear-approximation-of-efficiency-for-similar-non-endoreversible-cycles-to-the-carnot-cycle",totalDownloads:1506,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In the present paper the non-endoreversible Curzon-Ahlborn, Stirling and Ericsson cycles as models of thermal engines are discussed from the viewpoint of finite time thermodynamics. That is, it is propose the existence of a finite time of heat transfer for isothermal processes, but the cycles are analyzed assuming they are not endoreversible cycles, through a factor that represents the internal ireversibilities of them, so that the proposed heat engine models have efficiency closer to real engines. Some results of previous papers are used, and from the get expressions for the power output function and ecological function a methodology to obtain a linear approximation of efficiency including adequate parameters are shown, similar to those obtained in that previous paper used. Variable changes are made right, like those used previously.",signatures:"Delfino Ladino-Luna, Ricardo T. Páez-Hernández and Pedro Portillo-Díaz",downloadPdfUrl:"/chapter/pdf-download/49204",previewPdfUrl:"/chapter/pdf-preview/49204",authors:[{id:"45093",title:"Dr.",name:"Delfino",surname:"Ladino-Luna",slug:"delfino-ladino-luna",fullName:"Delfino Ladino-Luna"}],corrections:null},{id:"48967",title:"Thermal Hysteresis Due to the Structural Phase Transitions in Magnetization for Core-Surface Nanoparticles",doi:"10.5772/61043",slug:"thermal-hysteresis-due-to-the-structural-phase-transitions-in-magnetization-for-core-surface-nanopar",totalDownloads:1950,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"One important issue raised in magnetism studies is the thermal response of various magnetic properties. This topic is known as the magnetic thermal hysteresis (MTH) which is principally associated with magnetic phase transitions. The MTH is of particular interest for both quantum and applied physics researches on magnetization of nanomaterials. Hysteresis of the temperature-induced structural phase transitions in some materials and nanostructures with first-order phase transitions reduces useful magnetocaloric effect to transform cycling between martensite (M) and austenite (A) phases under application. In additional, the size, surface and boundary effects on thermal hysteresis loops have been under consideration for the development of research on nanostructured materials. Experimental data indicate that nanostructured materials offer many interesting prospects for the magnetization data and for understanding of temperature-induced M-A phase transitions. In this chapter, we have presented a review of the the latest theoretical developments in the field of MTH related to the structural phase transitions for the core-surface nanoparticles based on the fundamental formulation of pair approximation in Kikuchi version.",signatures:"Rıza Erdem, Songül Özüm and Orhan Yalçın",downloadPdfUrl:"/chapter/pdf-download/48967",previewPdfUrl:"/chapter/pdf-preview/48967",authors:[{id:"175119",title:"Prof.",name:"Riza",surname:"Erdem",slug:"riza-erdem",fullName:"Riza Erdem"}],corrections:null},{id:"49584",title:"Information Thermodynamics and Halting Problem",doi:"10.5772/61900",slug:"information-thermodynamics-and-halting-problem",totalDownloads:1698,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The formulations of the undecidability of the Halting Problem assume that the computing process, being observed, the description of which is given on the input of the ’observing’ Turing Machine, is, at any given moment, the exact copy of the computing process running in the observing machine itself (the Cantor diagonal argument). In this way an infinite cycle is created shielding what is to be possibly discovered - the possible infinite cycle in the observed computing process. By this type of our consideration and in the thermodynamic sense the equilibrium status of a certain thermodynamic system is described or, even created. This is a thermodynamic image of the Cantor diagonal method used for seeking a possible infinite cycle and which, as such, has the property of the Perpetuum Mobile - the structure of which is recognizable and therefore we can avoid it. Thus we can show that it is possible to recognize the infinite cycle as a certain original equilibrium, but with a ’step-aside’ or a time delay in evaluating the trace of the observed computing process.",signatures:"Bohdan Hejna",downloadPdfUrl:"/chapter/pdf-download/49584",previewPdfUrl:"/chapter/pdf-preview/49584",authors:[{id:"175060",title:"Dr.",name:"Bohdan",surname:"Hejna",slug:"bohdan-hejna",fullName:"Bohdan Hejna"}],corrections:null},{id:"48985",title:"Thermodynamics of Coral Diversity — Diversity Index of CoralDistributions in Amitori Bay, Iriomote Island, Japan and Intermediate Disturbance Hypothesis",doi:"10.5772/61064",slug:"thermodynamics-of-coral-diversity-diversity-index-of-coraldistributions-in-amitori-bay-iriomote-isla",totalDownloads:1770,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The relationship between coral distributions and physical variables was investigated in Amitori Bay, Iriomote Island, Japan. Amitori Bay is located in the northeast region of Iriomote Island, Japan. Broad areas of coral have developed in the bay, and their life forms, coverages, sizes, and species vary depending on their locations. In addition, Amitori Bay has no access roads, and the bay perimeter is uninhabited. Thus, this small bay, with its variety of environments and lack of human impact, is considered to be one of the most suitable areas for studying the relationship between coral distribution and physical variables.",signatures:"Shinya Shimokawa, Tomokazu Murakami, Akiyuki Ukai, Hiroyoshi Kohno, Akira Mizutani and Kouta Nakase",downloadPdfUrl:"/chapter/pdf-download/48985",previewPdfUrl:"/chapter/pdf-preview/48985",authors:[{id:"50555",title:"Dr.",name:"Shinya",surname:"Shimokawa",slug:"shinya-shimokawa",fullName:"Shinya Shimokawa"},{id:"175138",title:"Dr.",name:"Tomokazu",surname:"Murakami",slug:"tomokazu-murakami",fullName:"Tomokazu Murakami"},{id:"175139",title:"Dr.",name:"Akiyuki",surname:"Ukai",slug:"akiyuki-ukai",fullName:"Akiyuki Ukai"},{id:"175140",title:"Dr.",name:"Kouta",surname:"Nakase",slug:"kouta-nakase",fullName:"Kouta Nakase"},{id:"175141",title:"Prof.",name:"Hiroyoshi",surname:"Kohno",slug:"hiroyoshi-kohno",fullName:"Hiroyoshi Kohno"},{id:"175142",title:"Dr.",name:"Akira",surname:"Mizutani",slug:"akira-mizutani",fullName:"Akira Mizutani"}],corrections:null},{id:"49028",title:"Thermodynamics of Abiotic Stress and Stress Tolerance of Cultivated Plants",doi:"10.5772/60990",slug:"thermodynamics-of-abiotic-stress-and-stress-tolerance-of-cultivated-plants",totalDownloads:2247,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Plants, as living systems, depend simultaneously on their internal status and their surroundings. Changes in plants’ surroundings, generated by different environmental factors (abiotic stress), could perturb existing homeostasis, thus imposing stress. Abiotic stress includes heat, cold, freezing, flooding, drought (refers to water deficit), weak or strong light, oxygen deficiency or sufficiency, increased UV or other ionising rays, high salinity or acidity of the soil, deficiency or sufficiency of mineral elements, and presence of pollutants (xenobiotics). The effect of each abiotic factor depends on its severity, duration, developmental stage of the plant and its susceptibility to stress. During stress, requirements for energy increase (with increased intensity of respiration—domination of exergonic processes) as well as entropy. Variations in environmental factors could push the plant’s metabolism out of homeostasis. In order to reestablish it, smaller or higher amounts of energy are required. The intention to increase the yield (grain or biomass production) of cultivated plants requires additional energy for successful completion of their life cycle, which makes them especially susceptible to stressful environments. From this point, the necessity to develop tolerant genotypes, which require less energy for maintaining homeostasis, arises.",signatures:"Vesna Dragičević",downloadPdfUrl:"/chapter/pdf-download/49028",previewPdfUrl:"/chapter/pdf-preview/49028",authors:[{id:"35979",title:"Dr.",name:"Vesna",surname:"Dragicevic",slug:"vesna-dragicevic",fullName:"Vesna Dragicevic"}],corrections:null},{id:"49747",title:"The Planck Power – A Numerical Coincidence or a Fundamental Number in Cosmology?",doi:"10.5772/61642",slug:"the-planck-power-a-numerical-coincidence-or-a-fundamental-number-in-cosmology-",totalDownloads:1440,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Jack Denur",downloadPdfUrl:"/chapter/pdf-download/49747",previewPdfUrl:"/chapter/pdf-preview/49747",authors:[{id:"61206",title:"Dr.",name:"Jack",surname:"Denur",slug:"jack-denur",fullName:"Jack Denur"}],corrections:null},{id:"49741",title:"Absolute Zero and Even Colder?",doi:"10.5772/61641",slug:"absolute-zero-and-even-colder-",totalDownloads:1467,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Jack Denur",downloadPdfUrl:"/chapter/pdf-download/49741",previewPdfUrl:"/chapter/pdf-preview/49741",authors:[{id:"61206",title:"Dr.",name:"Jack",surname:"Denur",slug:"jack-denur",fullName:"Jack Denur"}],corrections:null},{id:"49006",title:"Foundation of Equilibrium Statistical Mechanics Based on Generalized Entropy",doi:"10.5772/60997",slug:"foundation-of-equilibrium-statistical-mechanics-based-on-generalized-entropy",totalDownloads:1465,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The general mathematical formulation of the equilibrium statistical mechanics based on the generalized statistical entropy for the first and second thermodynamic potentials was given. The Tsallis and Boltzmann-Gibbs statistical entropies in the canonical and microcanonical ensembles were investigated as an example. It was shown that the statistical mechanics based on the Tsallis statistical entropy satisfies the requirements of equilibrium thermodynamics in the thermodynamic limit if the entropic index z=1/(q-1) is an extensive variable of state of the system.",signatures:"A.S. Parvan",downloadPdfUrl:"/chapter/pdf-download/49006",previewPdfUrl:"/chapter/pdf-preview/49006",authors:[{id:"42547",title:"Dr.",name:"Alexandru",surname:"Parvan",slug:"alexandru-parvan",fullName:"Alexandru Parvan"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:[{id:"65",label:"highly cited contributor"}]},relatedBooks:[{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editedByType:"Edited by",editors:[{id:"35542",title:"Prof.",name:"Mofid",surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited 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Convective drying is one of the most effective methods for disperse material dehydration in the chemical, pharmaceutical, mining, and other industrial branches [1, 2, 3, 4, 5, 6]. The direct contact of the drying agent with high-temperature potential and dried material enables intensively to remove the surface and adsorption-bound moisture [3]. That is why drying is the only method for industries to achieve the required quality of the product.
Although during drying the energy consumption is the lowest, the convective dryers are more often used to dry disperse materials thanks to other numerous advantages [3, 4]. Provision of the active hydrodynamic regime in such dryers helps intensify the process without reduction of the economic efficiency of their operation and has the following advantages [7, 8, 9]:
Hydrodynamic stability of the process
Increase of the relative motion velocity of the interacting phases
The developed surface of the contacting phases
Approximation of the hydrodynamic model of flows in the device to the ideal displacement model
Reduction of the energy intensity of the process and metal intensity of devices
One should distinguish devices with various configurations of the weighted layer (fluidized bed, spouting, gravitational falling, vortex, etc.,) from the variety of the convective dryer constructions (described, e.g., in [7, 10]). Thanks to the developed surface of the phase contact, devices with hydrodynamic system are characterized with high intensity of the heat and mass transfer processes, lower non-energy costs, and have high specific productivity [7].
Besides, under conditions of the cost increase to prepare and to transport the drying agent, the possibility of its repeated use in the drying process is fundamentally important. Therefore it is necessary maximum to use the thermal potential of the drying agent during every contact with disperse material. It can be achieved while using the multistage drying devices with vertical sectioning of the workspace by the perforated shelf elements [7, 8, 11].
A solution to the permanent residence of the dispersed material in the “active” zone can be found through implementation of the multistage shelf dryers with vertical sectioning of the workspace (Figure 1).
Multistage shelf dryer: (1) case; (2) shelf.
In such devices, the conditions for the differentiated heat treatment of materials can be created owing to the drying agent potential and peculiarities of each stage (shelf) construction. So, moving the perforated shelf to the wall of the device, we approach to the device with fluidized bed, and moving it away from the wall and freeing its workspace, we approach to the device with the free intersection, such as pneumatic transportation dryers. The shelves increase the residence time of the dried material particles, either poured downward of the device or carried out upward of it. The shelves increase the velocity and turbulence of the gas flow, create a vortex motion in their location places, and increase the contact intensity between phases. The free space between the ends of the shelves and the walls of the device does not require special flows from the upper shelf to the lower one. Changing the free area of the shelve perforation, their tilt angles, the distance from the end of the shelves to the walls of the device, the number of shelves, and the distance between them vertically, it is possible to influence the intensity of the contact phases and to create different hydrodynamic regimes to weigh particles of the material both on individual shelves and heightwise the device. Therefore, it is possible to carry out the drying process of wet materials and its pneumatic classification in one device in order to remove small dusty fractions from the mixture [7].
The necessity to determine these features is due to the fact that before constructing an industrial sample of the gravitational shelf dryer it is necessary to determine its optimal design. In this case, the optimization criterion is to ensure the minimum required residence time of the dispersed phase in the working space of the dryer, which will complete the drying process to a predetermined humidity indicator. It is important to observe the condition, under which the “hydrodynamic” residence time of the dispersed phase in the workspace of the device should be no less than the “thermodynamic” time (this parameter is determined by the kinetics of the moisture removal process from the dispersed phase). Therefore, in order to keep the integrity of the dispersed particles, the “hydrodynamic” time should not exceed the “thermodynamic” time by more than 5–10%. By adjusting the hydrodynamic properties of the flow, an optimal construction of the gravitational shelf dryer is achieved, which meets the requirements of the optimization criterion.
Thus, the optimization calculation of the dryer consists of three blocks: hydrodynamic calculation (calculation of the residence time of a particle on a stage), kinetic calculation (kinetic parameter of the moisture removal), and calculation of drying efficiency.
Initial data (Figure 2):
Rate of gas flow,
Length of device,
Overall width of device,
Length of shelf,
Degree of perforation (free area),
Perforation hole diameter,
The tilt angle of shelf, γ (°)
The radius of the granule,
Granule density,
Gas density,
Acceleration of gravity,
Resistance coefficient,
Volumetric content of a dispersed phase in a two-phase flow,
The coefficient that takes into account the tightness of the flow,
Number of stages in dryer,
Moisture of the material
Moisture of the drying agent in
A fragment of the calculation scheme for the multistage drying: left figure—change of flows’ moisture: x, moisture of the disperse material; b, moisture of the drying agent, and right figure—construction of dryer’s workspace.
Hole area on the shelf (horizontal position) (m2)
The perforated area on the shelf (horizontal position of the shelf) (m2)
Number of holes on the shelf
Area of outloading clearance (m2)
Area of the gas passage holes in the shelf (inclined position of the shelf) (m2)
The relative area of outloading clearance
The relative area of the gas passage holes in the shelf
Rate of the gas flow in outloading clearance (m3/s)
Rate of the gas flow in holes in the shelf (m3/s)
Gas velocity in holes in the shelf (m/s)
Second critical velocity (m/s)
Velocity difference (m/s)
Time of material residence on the shelf (free movement) (s)
The empirical function of the effect of compression on the residence time of the particle in the working space of the device
Time of material residence on the shelf (straitened movement) (s)
The program Multistage Fluidizer® [12] used Hypertext Markup Language HTML, Cascading Style Sheet (CSS), and programing language JavaScript (including the library jQuery). HTML is presented as a tagging of web-based app, CSS page formatting. JavaScript is used to calculate and transfer data and to create animation and data validation effect. In the validation block of JavaScript, data accuracy is checked. In the block input info, the basic data field indices are accepted, and they are written to the object of input_information. In the block, calculation computations are carried out by Eqs. (1)–(15).
Index.html (Figure 3) is the main page of the web-based app. It is responsible for reflection of the main menu, for the main calculation of gas flow, and for jumping the other pages (an example of such page is presented in Figure 4), where the main dependencies between key features to calculate gas flow and resistance time of the material on the shelf are calculated and dependencies diagrams are formed.
The main page of the Multistage Fluidizer® software.
Calculation page of various parameter impacts on the particle resistance time in the device.
Having inserted data, data validity is tested, that is, if all data is correct, after keystroke CALCULATE data is processed given the above formulas, and we receive the result in a form of a computation table (Figure 5).
Results of calculation.
After changes of indices
Calculation of way length, which particle undergoes on the shelf during the specified period of time.
In JavaScript, one uses libraries jQuery and table2excel, objects for data recording, methods .val() .append() to read and to insert indices to fields, methods .removeClass() and .addClass() to delete and to add classes, and method .animate() for work with animation to create an animation effect for any digital CSS feature of the element.
In order to calculate the kinetic parameter of the moisture removal (the moisture-yielding capacity coefficient), let us use the following algorithm.
It is proposed [8] to use the following equation for calculation of
where
In general, the criteria equation of the drying process can be written as follows:
where
The drying process effectiveness on the i-stage of the dryer is presented by the ratio of differences between the moisture contents of the disperse material before and after the drying
Some graphic dependencies are shown in Figure 7. The program receives two- and three-dimensional dependency graphs.
Examples of calculation results.
In general dependency diagrams, features for free and constraint motion of particles have one functional dependence. The particle resistance time has enough narrow diapason at every stage (shelf) in free motion regime and is calculated by second units. In the constraint motion regime of particles, the residence time is greatly increased at every stage. The abundant ratio of particles in the two-phase system has a definite impact on this index. That is why, while defining the optimum performance of the device, it is necessary to define the workspace size of the granulating or drying device to high accuracy.
The impact made by some constructive features of the shelf dryer during the residence time of the dispersed material (Figure 7) is shown below.
The change of the shelf tilt angle to the horizon affects the redistribution of the gravity components: enlargement of it leads to an increase of the gravity rolling component and vice versa. It should be mentioned that the tilt angle of the shelf may have a minimum value that complies with the natural slope angle of the material. As the tilt angle of the shelf decreases, the residence time of the dispersed material gradually increases. It leads to longer contact with the drying agent’s flow.
Changing the gap between the edge of the shelf and the dryer’s wall significantly influences the change of the residence time of the dispersed material on the shelf. If the gap increases, the contact time of the dispersed material with the drying agent will be reduced due to the decrease in the length of the material movement distance on the shelf. In this case, the operation of the rolling component of the dispersed material velocity lasts for a shorter period and at the end of the shelf is replaced by the full gravity. Thus, the material moves down, and only the ascending gas flow force resists its fall.
The analysis of the calculations regarding the effect, made by the free cross-sectional area of the shelf on the drying process efficiency, showed the following. Reducing the free cross-sectional area of the shelf leads to an increase of the drying agent’s ascending motion velocity in the holes. In this case, the action of the drying agent’s ascending flow slows down the progressive motion of the dispersed material on the shelf, compensating for the rolling component of its gravity. The pulse component of the dispersed material displacement decreases, and the trajectory changes to a pulse-forward one. The trajectory length of the dispersed material motion increases, the time of its contact with the drying agent is extended.
As the diameter of the perforation holes decreases, the effect of the drying agent’s ascending flow increases, in which the pulse component of the dispersed material motion trajectory decreases, and the forward increases. Thus, the trajectory length of the dispersed material motion increases, and the contact time with the drying agent is extended. It should be noted that with the further reduction of the perforation hole diameter, the action of the drying agent’s ascending flow begins significantly to outweigh the effect of the gravity rolling component. It leads to the formation of the second transitional mode and the ablation mode in the shelf dryer’s operation.
The calculated values of the mass transfer coefficient β from Eq. (16) depending on the velocity of the drying agent’s motion are demonstrated in Figure 8.
Dependence of the mass transfer coefficient on the drying agent’s motion velocity.
The graphical dependency from Eq. (17) shows (Figure 9) that coefficient
Graphical dependency
Taking into account the obtained values of the coefficient
The organization of the drying agent’s motion may have a considerable influence on the quality indicators of the dried material and the properties of the drying agent. That has evolved several studies, the results of which are presented in Figures 10–13. Their analysis enables us to select the method to organize the drying agent’s motion, which consumes the least energy and ensures the necessary complete removal of moisture from the disperse material.
Influence of the drying agent recirculation method on the change of the moisture content in the disperse material.
Influence of the drying agent recirculation method on the change of the moisture content in the drying agent.
Influence of the drying agent recirculation method on the temperature change of the disperse material.
An influence of the drying agent recirculation method on the temperature change of the drying agent.
The analysis of the figures shows that the features of the dispersed material and the drying agent are changed according to one law; each of the technological indicators in the drying agent differently influences the intensity of the increase or decrease of parameters. The figures show that there is no function extremum on the graphical dependencies, which is explained by the regularities of the convective drying kinetics—the parameters’ change of the contacting flows in each of the periods occurs monotonically with different intensity on separate sites depending on the dehydration conditions.
Different constructions of the shelves (Figure 14) enable us to control the residence time of the dispersed phase in the dryer’s workspace.
Constructions of shelves in the multistage gravitational shelf dryer [
Block scheme of the algorithm to calculate the multistage gravitational shelf dryer is represented in Figure 15.
Block scheme of the algorithm to calculate the multistage gravitational shelf dryer (symbol *** shows the blocks which are described in this work).
During the optimization calculations, the necessity to obtain certain empiric dependencies has been revealed. They would identify some quantities, especially important for the shelf dryer’s design development.
The experimental investigations were carried out on a shelf dryer model, the design parameters of which corresponded to the picture in Figure 1. Experiments to study the properties of the two-phase flow hydrodynamics in a shelf device were carried out at gas flow velocity of 1–5 m/s, specific capacity on the source material 6–10 kg/(m2 s).
At low gas flow velocities of 0.5–1 m/s, particles of the material move along the surface of the sloping shelf at a velocity of 0.2–0.3 m/s in the form of a rapidly “skipping” layer. The particles of the material are braked at the wall of the device in the discharge space and are accumulated on the surface of the wall (Figure 16a) after moving over the surface of the shelf. This accumulated layer is blown by a gas jet, which is formed by a discharge gap between the lower end of the shelf and the wall of the device. As the gas flow velocity increases to 2.5–4 m/s, the porosity of the layer decreases to 0.75–0.8, and the concentration of particles in the layer increases to 40–50 kg/m2 s.
The photo of the hydrodynamic modes of the shelf dryer: (а) “gravitationally falling layer” regime and (b) “weighted layer” regime.
Small particles, in which the inertia force during their discharge from the surface of the sloping shelf is insufficient to overcome the kinetic energy of the gas jet, are picked up by the jet and move along a curved path to the upper part of the device—the separation zone. On the photo (Figure 16a), it is seen by the distinct tracks of the trajectory. Large particles, overcoming the aerodynamic drag of the gas jet, fall out of the layer through the discharge space down. The described hydrodynamic regime is called “gravitationally falling layer.” This mode is implemented on the shelves, installed with a width of the discharge gap (0.3–0.5) L and a free area of 5–10%. Therefore, the maximum efficiency of small fraction ablation by the gas flow is achieved (Figure 17). The velocity of the complete ablation of the small fraction without large particles in it—the second critical velocity—is as follows:
The influence of the design (constructive) parameters of the shelf on the extraction efficiency of the fraction less than 1 mm. The free area of the shelf: 1–4, respectively, 0, 5, 15, and 30%. The tilt angle of the shelf is 30°. Material is a polydisperse mixture of the granular superphosphate.
where Ar is the Archimedes criterion,
Reducing the width of the discharge space up to (0.15–0.2) L and increasing the free area of the shelf up to 15%, owing to the growing kinetic energy of the gas jet, the continuously circulating vortex layer of particles above the sloping shelf surface is formed (Figure 16b). Therefore, the particles of the material are moving on the surface of the sloping shelf in the form of the tightened (compressed) layer at the velocity of 0.05–0.15 m/s, and in the area above, the discharge space—in the form of weighted, intensively circulating layer. The porosity of this layer is 0.65–0.7 (coincides with fluidized systems’ porosity), and concentration of the particles in the workspace of the device is 160–280 kg/m3. The described hydrodynamic regime is called the “weighted layer.” The velocity at which the “weighted layer” mode is implemented—the critical velocity when the weighting is started is calculated as follows:
where
The effect of the gas flow velocity on the intensity of the interphase heat transfer process is represented by the dependence of the Nusselt criterion on the Reynolds criterion—Nu = f (Re) (Figure 18). These dependencies are described with the following criteria equations:
Influence of the gas flow velocity on the interphase heat transfer intensity: (1) “gravitationally falling layer” mode, shelf parameters: L1/L = 0.5; fa = 5%; (2) “weighted layer” mode, shelf parameters: L1/L = 0.15; fa = 15%.
Equations (24) and (25) are valid for 0 ≤ Re ≤ 500.
The above dependencies in the “weighted layer” mode show that the values of the Nusselt criterion are significantly higher than values, which are peculiar for the “gravitationally falling layer” mode. The sufficiently high intensity of heat and mass transfer processes in the “weighted layer” mode is explained by the fact that in this mode the gas jet entering the weighted layer through the discharge gap at sufficiently high velocity has the greatest intensifying effect. Measures of the single-phase flow velocity, carried out by a thermal anemometer in the intersection above the shelf, showed that at gas jet velocities in the discharge space of 6–12 m/s, local heat transfer coefficients at the site of material particles contact with the gas jet are 400–500 W/(m2 K). These values are peculiar for the intensive heat transfer conditions in the core of the spouting layer and exceed the average heat transfer coefficients for fluidized beds (100–400 W/(m2 K)) and the pneumatic transportation mode (100–200 W/(m2 K)).
The rapid evaporation of moisture in the zone above the discharge space leads to some temperature drop of the hot gas before it contacts with the main layer of particles, weighted above the shelf. Experimental studies show that the heating temperature of particles in the zone of contact with the gas jet entering the discharge gap is 1.5–2.0 times higher than that in a weighted layer on the surface of the shelf. It uses a drying agent with higher inlet temperature (1.5–1.8 times higher than melting temperature) than it is acceptable for dryers of the fluidized bed, without fear of the thermal damage of particles.
The investigated construction of the shelf dryer was tested when drying the fine- and coarse-crystalline potassium chloride, sodium pyrosulfite, iron, and nickel powders (Table 1).
Material | The velocity of the drying agent, m/s | Humidity, % wt | Moisture removal intensity, kg/(m3 h) | ||
---|---|---|---|---|---|
Source material | Undershooting | Ablation | |||
Fine-coarse potassium chloride: | |||||
1.32 | 6.1 | 0.35 | 0.24 | 421 | |
Coarse-crystalline | 1.5 | 6.1 | 0.1 | 0.06 | 462 |
1.45 | 8.0 | 1.2 | 0.2 | 1025 | |
1.9 | 7.0 | 0.1 | 0.17 | 527 | |
2.1 | 8.0 | 0.11 | 0.1 | 1173 | |
2.3 | 7.0 | 0.14 | 0.1 | 528 | |
Sodium pyrosulfite | 2.8 | 5.0 | 0.5 | 0.1 | 250 |
3.3 | 5.0 | 0.5 | 0.1 | 346 | |
3.5 | 6.0 | 0.6 | 0.2 | 258 | |
Iron powder | 2.0 | 10.0 | 0.34 | 0.3 | 1826 |
Nickel powder | 2.3 | 11.3 | 0.4 | 0.3 | 600 |
Results of the drying of the granular materials in the shelf dryer.
The shelf dryer, where experimental tests were carried out, is a vertical rectangular-sectioned shaft, inside which the sloping perforated shelves are located in cascade on opposite sides (Figure 1). Wet material is fed by the batcher to the upper shelf, is weighed above it, and is divided into small and large fractions. The upper shelf works in the hydrodynamic regime of the “gravitationally falling layer.” In this mode, the dedusting process of materials, i.e., the removal of small particles from the initial mixture by the minimum interface, is effectively carried out. The minimum interface for shelf devices is 50–70 μm. The small particles are carried away by the drying gas agent into the separation space and then captured by a cyclone in which they are dried. Large particles fall down through the discharge space to the lower shelf.
When drying the materials, which are prone to the formation of lumps and strongly sticking to surfaces, the distance from the delivery point of the wet product into the device to the upper shelf has to be at least 0.3–0.5 m. The material, passing this distance, breaks up into small pieces and is partially dried. A hydrodynamic regime of the “weighted layer” is created on the lower shelf, in which, due to the intensive circulation and mixing of particles in the layer, the drying process is effectively carried out. The longer residence time of the particles in this layer also contributes to it.
The wet material, discharged from the upper shelf, enters the lower shelf from the top of the weighted layer, is drawn into the circulation, and is dried quickly. The share of the dried material falls through the discharge space into the hopper, in which a large fraction of the dried product is collected.
Thanks to the shelf contact elements, shown by the data of Table 1, the drying process takes place at the drying agent’s moderate velocities (maximum 3.5 m/s) and at a large moisture intensity of the dryer’s workspace which is up to 1000–1500 kg/(m3 h). Due to the intensive contact between phases in the shelve devices, the drying process is carried out at high specific loads of up to 15–20 kg/(m2 s), significantly exceeding the specific loads of 0.1–1.5 kg/(m2 s) for fluidized bed devices. The specific consumption of the drying agent in the shelf dryers reaches 0.5–0.7 m3/kg, and the hydraulic resistance is 1300–1500 Pa, respectively, against the values of 1.4–2.8 m3/kg and 1800–2200 Pa for fluidized bed devices. The working path of the pneumatic pipe dryer, in which energy is expended to accelerate and to lift the drying material, has a hydraulic resistance of 1600–2000 Pa.
An additional advantage of shelf dryers is the simultaneous dedusting of the drying material. Fine-crystalline potassium chloride, containing 7–10% of the small fraction with a particle size of less than 100 μm in the initial mixture, after processing in a shelf device at a gas flow velocity of 1.4–1.5 m/s, had 1.2–5.5% of the small fraction in the final product (undershooting) and 60–80% of the small fraction in ablation. Coarse-crystalline potassium chloride, containing 4–10% of the small fraction with a particle size of less than 100 μm in the initial mixture, had 2–5% of the small fraction in the final product (undershooting) at a gas flow velocity of 1.3–1.4 m/s and 58–65% of the small fraction in the ablation. The extraction degree of the small fraction into the ablation was 70–90%. When the gas flow velocity exceeds 1.5 m/s in the final product, the small fraction is practically absent, and the content of the coarse fraction (more than 100 μm) in ablation is 3–5%.
The small fraction was completely extracted from the polydisperse mixture of granulated superphosphate containing up to 20% of the small fraction with particle sizes less than 1 mm, after processing in the shelf device at a gas flow velocity of 3.5–3.8 m/s, into the ablation. Therefore, the extraction degree of the small fraction into ablation was 80–85%.
In order to prevent the coarse fraction ablation by the gas flow and increasing the residence time of particles in the separation space for drying the ablative fractions, the upper section with a constant intersection was replaced with a conical free intersection [16] or with shelf contact elements [17].
Thus, the shelf dryers achieve the higher technological effect than typical constructions of the fluidized bed dryers and pneumatic pipe dryers, with less energy, capital costs, and sizes.
The convective shelf dryer construction with active aerodynamic processing modes is proposed. The developed engineering method for the shelf dryer calculation made it possible to define the constructive parameters of the device, ensuring the minimum required drying time of the wet material in the device to a predetermined humidity index. The demonstrated author’s program Multistage Fluidizer® for computer implementation of the engineering calculation method made it possible to optimize the constructive and operating parameters of the drying process in the shelf device. It was shown that a shelf dryer should have, for example, three shelf contacts with various widths of the discharge space and various free areas of the shelves.
The author shows various hydrodynamic regimes to weigh particles of a material by a gas flow, depending on the constructive parameters of shelf contacts.
The effectiveness of the shelf device to carry out the drying and dedusting processes of granular and powder materials simultaneously was experimentally proven.
This research work has been supported by the Slovak Grant Agency VEGA Grant No. 1/0731/16 “Development of Modern Numerical and Experimental Methods of Mechanical System Analysis,” by Cultural and Educational Grant Agency of the Slovak Republic (KEGA) Project No. KEGA 002TnUAD-4/2019, and by the Ministry of Science and Education of Ukraine under the project “Small-scale energy-saving modules with the use of multifunctional devices with intensive hydrodynamics for the production, modification and encapsulation of granules,” Project No. 0119U100834.
The authors declare that they have no competing interests.
Cystic fibrosis (CF) is an autosomal recessive condition that results from mutations in the cystic fibrosis transmembrane conductor regulator (CFTR) gene located on the long arm of chromosome 7. The gene was identified 30 years ago and since then over 2000 CFTR mutations have been discovered with more than 300 known to be disease causing [1, 2]. The commonest mutation is Phe508del (F508del; c.1521_1523delCTT), where a phenylalanine is substituted at position 508 on chromosome 7. Worldwide approximately 80–90% of individuals with CF have at least one copy of the Phe508del-CFTR mutation, although mutation rates varying depending upon the population cohort [3, 4, 5].
CF is a multi-system disease with the highest disease prevalence being in Europe, North America and Australia. There are approximately 80,000 people with CF worldwide. The disease is characterized by chronic airway infection, pancreatic insufficiency and malnutrition, diabetes, liver disease, absent vas deferens and premature death.
Due to the multi-system nature of the disease, treatment has classically focused on therapies and systems of care that aim to improve salt and fluid balance and nutritional status, alongside reducing airway inflammation and lung parenchymal destruction. These multi-disciplinary management approaches have been instrumental in the improvements seen in life expectancy. The median predicated survival of an individual born today with CF is 47 years, compared with 20 years at the time when CFTR was discovered in 1989 [2]. However, to have a true impact upon the management of these patients and to alter the disease trajectory, treatment options needed to also include approaches targeting the underlying genetic mutation.
This chapter will include a review of the structure of the CFTR protein, its biosynthesis and the pathophysiology of CF so as to provide a basis from which to discuss the various therapeutic strategies that have more recently been developed for modulating CFTR protein function. Also, a discussion regarding gene therapy will be included so as to enable contrasts and comparisons to be made between the different therapies being evolved to address the underlying genetic defect in CF patients.
CFTR codes for a complex protein, which is present in every nucleated cell of the body, however it is normally concentrated on the apical membrane of epithelial cells, primarily within the glandular epithelia. High expression of this apical anion channel is seen within the lungs, pancreas, gastrointestinal tract, vas deferens and sweat glands; reflecting the main organs affected in CF [6].
The CFTR protein is a large, unique member of the subclass C family of the ATP binding cassette (ABC) transporter proteins, which functions as an ion channel rather than an active transporter protein [7, 8, 9]. It consists of two membrane-spanning domains (MBDs) that form the ion channel. These domains are both connected to two cytoplasmic nucleotide-binding domains (NBD1 and NBD2), which function to gate the channel. This conformation of two MBDs and two NBDs that hydrolyse ATP are typical for most ABC transporters. However, CFTR has an additional cytoplasmic regulatory domain (R domain), inserted between NBD1 and MSD2 linking the two transporter domains. Phosphorylation of the R domain by protein kinase A enables channel opening to occur and channel activity is increased upon phosphorylation. Once phosphorylation has taken place, ATP binds to the NBDs resulting in the two NBDs forming tightly interacting dimers, which gates the channel. These movements are transmitted to the MBDs causing the ion pore to open. Channel closure results from ATP hydrolysis. The exact mechanisms underlying the regulation of the R domain and ATP-dependent gating are still not completely understood [10, 11].
CFTR protein synthesis is a complex process, in part related to the size of the functional protein. As with all protein synthesis, transcription of the CFTR DNA takes place within the nucleus to create the messenger RNA (mRNA), which is transported across the nuclear membrane to the cytosolic ribosomes. There the initiation of translation occurs to create a 1480-amino acid polypeptide chain based upon the genetic code. Initially a 135- to 140-kDa core-glycosylated precursor is produced (immature CFTR). CFTR biosynthesis then proceeds through the endoplasmic reticulum (ER) followed by the Golgi apparatus to a mature 150- to 160-kDa CFTR form which has undergone conformational folding [12]. During the secretory pathway through the ER to the Golgi and then on to the cell membrane various post-translational modifications take place (Figure 1).
Cell biology of CFTR - abnormal CFTR protein results in the uncoupling of CFTR dependent processes at all levels from intracellular dynamics to cell membrane function. Reproduced with permission of the © ERS 2020: European Respiratory Journal; DOI:
The maturation process to create the final relatively compact CFTR protein structure is inefficient and slow. Less than 30% of newly synthesized wild-type (wt) immature CFTR molecules develop into mature CFTR proteins. For folding of the polypeptide chain to occur chaperones are required, in particular the 70 k-Da heat shock proteins (HSP70) and calnexin. In cells of individuals with the Phe508del-CFTR mutation, almost all immature molecules fail to reach final maturity and thus are degraded. This is the due to the quality control mechanisms in place within the ER, specific signals and distinct processes exist that recruit misfolded proteins to the ER-associated degradation as a final endpoint. These proteins are then directed for degradation via the ubiquitin-proteasome pathway [12, 13, 14] (Figure 1).
Certain steps within the CFTR biosynthesis pathway are still unknown, however, data does support each domain folding independently. The native structure develops through a co-translational mechanism, possibly together with post-translational processes that take place to create the compactly folded domains. Domain-domain interactions are key in the creation of conformationally correct CFTR [15]. Furthermore, it appears that CFTR is more sensitive to mutations in NBD1 compared with homologous mutations in NBD2, leading to issues with the conformational maturation of the whole CFTR protein. For example, the deletion of the Phe508 does not appear to grossly alter the structure of NBD1 but subsequent issues arise during the maturation process, possibly through the disruption of the interaction between NBD1 and NBD2 and despite each domain folding independently. Maturation thus requires precise folding of each domain together with the correct inter-domain assembly to create a stable structure that will not be submitted to ER-associated degradation [13, 16].
If the protein passes through all the checkpoint steps within the ER, it can exit and be transported through the Golgi apparatus in vesicles where the removal and addition of new glycan units takes place, increasing the molecular size of CFTR. It is becoming clear that some wt-CFTR might bypass these processes in the delivery pathway to the plasma membrane. Once at the membrane, levels of CFTR vary depending upon the balance of anterograde trafficking, endocytosis and recycling. Recycling of internalized CFTR to the plasma membrane is thought to assist with sustaining a functional pool of CFTR at the membrane level [15].
CFTR functions as a chloride and bicarbonate channel. Loss of functional CFTR proteins result in reduced chloride efflux from epithelial cells leading to depletion of the cell surface fluid and altering its pH and osmolarity. CFTR also regulates the activity of various other key processes within the cell, including the activity of other ion channels, such as the sodium epithelial channel (ENaC; the amiloride-sensitive sodium channel). Suppressed CFTR activity can lead to unopposed reabsorption of sodium and water via ENaC, causing additional dehydration of the cell surface layer [6]. Mucociliary clearance is further delayed due to abnormally adherent mucus. Dysfunctional CFTR also impacts upon mitochondrial function, the innate immunity and dysregulates inflammation [17, 18, 19]. Within the airways, this results in an environment that is susceptible to unchecked inflammation and chronic bacterial infection.
Although multiple processes both intra- and extra-cellularly are altered by dysfunctional CFTR proteins, chloride transport at the cell surface is generally considered to be the major driver of the pathophysiological disease. Functional chloride channel changes are thus likely to represent an easily accessible surrogate marker of all processes affected in CF, with sweat chloride testing being relatively easy to perform. In vitro studies have shown that only 6–10% of residual CFTR function is required to restore chloride transporting properties seen in 100% correct cells, with cell-cell coupling providing a means of amplification of the functional properties [20]. Individuals with CF who have approximately 10% CTFR expression per cell do not generally develop lung disease or the full range of classical CF disease. To date, it is unclear whether low level expression (10%) of CFTR in all cells is comparable to 10% of CFTR cells with full correction [21]. In addition, even individuals with a single CFTR mutation may have organ dysfunction in the context of a second “hit” such as smoking [22].
The general identification of mutations in the structure of CFTR has been centralized for clinician reference. CFTR2.org identifies over 2000 variants of the protein, of which over 400 are disease-associated. The majority of variants are rare and not confirmed to be disease-associated, however the large number of variants indicates the lack of stability of the CFTR gene in population dynamics [1].
Classification systems of common CFTR mutations have been developed to assist with understanding of the consequential molecular defect. The established classification system includes six different classes (Figure 2). Different mutations can result in no functional protein production, impaired protein trafficking, altered channel gating, decreased channel conductance, reduced protein synthesis and decreased protein stability [6]. Each class confers a different disease severity, which is related to the degree of CFTR dysfunction and has prognostic implications for patients. However, each mutation may have features of more than just one class. For example, Phe508del is predominately a class II mutation but also has both class III and class VI properties. More recently, other classification systems have been proposed, which subdivide class I mutations (no functional CFTR protein) into two groups so as to take into account whether the mutation leads to no mRNA or no functional protein [23].
CFTR classification table. The classification systems divide mutations into discrete groups determined by the predominant CFTR defect. However, these systems may not be mutually exclusive for all mutations. For example, the p.Phe508del-CFTR is predominately class II but does also have some class III and class VI properties. Reproduced with permission of the © ERS 2020: European Respiratory Journal; DOI:
Traditional CF care has focused upon the management of the systems affected in individuals with CF. However, the identification of the CFTR gene enabled researchers to focus on treatments strategies, which could address the underlying genetic defect. The major cause of morbidity and mortality in CF is secondary to lung disease. Hence, if abnormal CFTR in the lungs could be replaced with wt-CFTR during the neonatal period, prior to parenchymal lung damage or bacterial colonization, morbidity and mortality could be significantly altered within the CF population [24]. Various approaches have been investigated within the field of “genetic medicines” and unfortunately to date none are a viable treatment option outside of clinical trials.
“Genetic medicines” comprise of four different treatment approaches:
The potential benefit of these therapies is that theoretically they should be suitable for the treatment of all individuals with CF, regardless of genotype. Currently gene therapy has made the greatest advancement towards being a clinical treatment and so the main focus of this section will be around gene therapy.
As the respiratory system is so central to CF disease and because initial thoughts were that gene therapy targeting the lungs would be easy to deliver, locally directed gene therapy to the respiratory epithelium was the method of choice. Furthermore, gene therapy can complement any CFTR causing mutation. However, for such treatment to be successful various issues had to be addressed, including the choice of delivery vector, method of delivery to the airways, translocation of the genetic information and ultimately ensuring that there was appropriate expression of the normalized CFTR gene [25]. These various issues will each be discussed to provide insight in the difficulties experienced in trying to develop “genetic medicines.”
The lungs are comprised of terminally differentiated epithelial cells, which are slowly replaced by stem/progenitor cells. Any form of gene therapy must be able to be either repeatedly delivered to the terminally-differentiated cell surface or be able to alter the stem/progenitor cells within the lungs. However, the lung has evolved physical and immune mechanisms to protect against pathogens and particulate materials, which impacts upon choice of vector delivery [26, 27].
Delivery vectors are largely either viral or non-viral in nature with viral ones felt to be more efficient. This is because they have evolved to overcome the barrier mechanisms present within the lungs. Adenoviruses (Ad) and adeno-associated viruses (AAV) have a natural trophism for the lungs, are DNA-based and thus were the initial choices to study. Adenoviruses are small in size and thus to insert the CFTR DNA correctly within the adenoviral genome, viral DNA must be removed, impacting upon the viral cytopathic effect. These vectors were found to have poor efficacy due to the pre-existing and induced immune responses, and thus cannot be repeatedly administered as required for these treatments because of the short life span of bronchial epithelial cells.
Other viral vectors that have been investigated are recombinant lentivirus (rLV). These agents are RNA-based and can integrate into the genome. This can be advantageous as it ensures that the vector is passed down the cell lines during division but it also does have the risk of inducing insertional mutagenesis [21, 26, 28]. However, ultimately other vectors were needed to be formulated, ones which had a minimal risk of immunogenicity and thus could be repeatedly administered.
Non-viral gene transfer agents complexed to plasmid DNA were therefore developed [21, 29]. These have been more successful than their viral vector counterparts and have been investigated in Phase IIb studies. Patients who were 12 years and older were treated with the non-viral CFTR gene-liposomal complex pGM169/GLG7A as a nebulized therapy over a one-year period. The repeated nebulization each month resulted in a reduction in the progression of CF lung disease by a modest amount when compared with placebo. The percentage change in the forced expiratory volume in 1 second (FEV1) over 12 months was −0.4% versus −4.0% in the placebo arm. Hence, although no improvement in lung function was seen, this study was promising as rate of lung function decline does impact morbidity and mortality in CF. However, disappointingly also there were no improvements in quality of life measures [30].
As described in the above study the agents utilized were delivered via inhalation methods. This has been found to be the easiest method for repeated treatment applications. However, difficulties have arisen ensuring adequate lung deposition of drug, related to particle size and the type of nebulisers used. Additionally, any aerolised drug delivered must retain its biological function post-delivery [31, 32].
Other strategies for ensuring corrected CFTR protein production is through mRNA therapy and mRNA repair as described above. The benefit of these approaches is that they do not require translocation of the therapy across the nuclear membrane. Nanoparticle-chemically modified mRNA has resulted in lung function improvements in animal models without any immune reactions despite repeated applications. Also, there is evidence that these therapies can restore chloride channel activity [33, 34]. Ongoing work and investigation are required prior to these options being viable in the clinical setting.
CFTR modulator agents are small molecules which ‘modulate’ the function of the abnormal CFTR protein. Unlike gene therapy, they do not alter the CFTR gene. However, these agents do manipulate the underlying genetic consequence of CF mutations. Currently two different classes of modulator agents have been developed;
potentiators which ‘potentiate’ the cAMP-mediated gating of the CFTR channel; and
correctors which ‘correct’ defects in protein trafficking.
High-throughput drug discovery programs enabled the development of such agents. These discovery programs were established to identify active compounds (“hits”) from large chemical libraries suitable for industrial-scale screening. High-throughput screening (HTS) assays need to be robust, have high throughput using small sample volumes together with adequate sensitivity, reproducibility and accuracy to ensure differentiation between a very large amount of compounds [35]. Ion channels are key targets for drug design and thus HTS have been an important part of such drug discovery processes, including for CF [36, 37].
The two classes of small molecules for CFTR protein modulation were identified via HTS techniques from libraries that consisted of chemically diverse drug-like and lead-like compounds acquired from both commercial vendors and internal medicine chemistry programs. If compounds had an activity >2.5 standard deviations (SD) from the mean, then they received further testing. For example, from ~164,000 synthetic compounds initial screened, approximately 100 were suitable for further study in one study [38]. The molecules identified were optimized and evaluated in terms of pharmacokinetics and toxicology [39, 40].
The first small molecule clinically available for individuals with CF following HTS was Ivacaftor (Kalydeco®). It is an oral CFTR potentiator agent, which can be given to CF individuals who have gating, residual function, splice or conduction mutations [41, 42, 43, 44]. It was originally developed for the Gly551Asp-CFTR mutation (G551D; a class III mutation), which results in defective cAMP CFTR channel gating. The gating of the channel reflects the opening and closed states of the CFTR protein. If gating is defective, then a low probability of CFTR channel opening occurs and in turn reduced overall CFTR function. Ivacaftor treatment results in increased chloride transportation across the cell membrane by improving channel gating and thus the time that activated CFTR channels remain open.
The initial phase 3 studies in individuals aged 12 years and older (STRIVE) and those aged between 6 and 12 years of age (ENVISION) evaluated ivacaftor or placebo in patients with at least one Gly551Asp-CFTR mutation. STRIVE identified a significant improvement in percentage predicted (pp) FEV1 in the treatment arm of 10% at 24 weeks (primary endpoint) that was maintained at 48 weeks. This was together with a 3 kg weight gain, an 8-point increase in the Cystic Fibrosis Questionnaire Revised (CFQ-R) score (an increase in the score out of 100 reflects an improvement in quality of life with a 4-point change being clinically relevant) alongside a reduction in sweat chloride to below the definite diagnostic threshold for CF to a mean of 47.8 mmmol/l [41]. Similar results were demonstrated in children in ENVISION [45]. Participants from both of these studies were then enrolled into the open-labeled extension study (PERSIST) where all individuals received ivacaftor therapy. These individuals maintained the improvements in lung function, weight and exacerbation rates at 144 weeks [46].
Such exceptional clinical outcomes were a major advancement in the treatment options for individuals with CF. However, initially modulator therapy was only suitable for approximately 5% of CF individuals as it was only available for gated mutations. Agents that could alter abnormal protein trafficking together with CFTR channel gating and cell membrane surface stability that results from the Phe508del-CFTR mutation (class II mutation) would have a far greater impact upon the CF community. As multiple stages in the CFTR conformational maturation process are affected with the Phe508del-CFTR mutation, different treatment approaches were needed.
HTS therefore progressed to evaluating agents that would be suitable for other mutation classes, focusing on agents could have an impact on dysfunctional protein trafficking [38]. Lumacaftor is an oral corrector agent, which in vitro studies have demonstrated can corrects protein misfolding [47]. However, monotherapy with either ivacaftor or lumacaftor did not lead to clinically relevant improvements in individuals homozygous for the p.Phe508del-CFTR mutation [48, 49].
As monotherapy only lead to minimal clinically relevant outcomes for Phe508del-homozygotes, the argument strengthened for the use of lumacaftor in combination with ivacaftor. Hence, these two therapies were trialed in combination (Orkambi®). Phase 3 multicentre studies (TRAFFIC and TRANSPORT) of this combination versus placebo elicited a modest gain in absolute pp. FEV1 of 3% at 24 weeks (primary endpoint) together with significant increases in body mass index (BMI) [50]. The lung function increase being comparatively small to that seen with ivacaftor for gated mutation. However, importantly the 96-week open label extension study (PROGRESS), where all individuals within the initial trials received lumacaftor in combination with ivacaftor, did demonstrate a 42% reduction in the annual rate of lung function decline when compared with matched US registry controls [51]. As rate of lung function decline is known to correlate with morbidity and mortality, this is still a significant outcome [52, 53].
Although lumacaftor in combination with ivacaftor is associated with stabilization of lung disease together with weight improvement, patients can experience various side-effects. Respiratory related adverse events were the commonest complications in the trials and up to 7% of patients discontinued treatment in PROGRESS. In real-world experiences, there have been even higher discontinuation rates of up to 30% [54, 55]. Also, lumacaftor is a potent inducer of the CYP3A4 enzymes and can have interactions with various concurrent medications. Development of other corrector agents with an improved side-effect profile and the potential for enhanced correction of the protein trafficking were therefore required.
This led to the development of tezacaftor, another small molecule corrector agent. Tezacaftor in combination with ivacaftor (Symdeko®/Symveki®), for individuals homozygous for the Phe508del-CFTR mutation, when compared with placebo resulted in a 4% absolute improvement in ppFEV1, together with a five-point improvement in CFQ-R scores but without any significant change in BMI (EVOLVE). Although the increments in lung function were still not as substantial as that seen in ivacaftor use for gating mutations, the adverse events were much lower than with lumacaftor/ivacaftor treatment. The discontinuation rate in the active treatment arm was only 2.9% and none of these were due to respiratory events [56, 57]. It thus appears that the corrector lumacaftor has a poorer side-effect profile than tezacaftor, rather than it being a complete class effect. Tezacaftor/ivacaftor can also be given to patients who have certain residual function and splice mutations (
The combination corrector therapies described, enable individuals with the commonest CF mutation the potential of receiving modulator therapy. However, lumacaftor/ivacaftor and tezacaftor/ivacaftor do not fully restore CFTR protein function. Furthermore, there is still no small molecule therapy for 30% of the individuals with CF who are heterozygotes for Phe508del and have a minimal function (MF) mutation. MF mutations give rise to either the production of defective proteins or no protein production. They include insertion, deletion, nonsense and canonical splice mutations. As up to 90% of CF individuals have one Phe508del mutation, if small molecule therapy could significantly increase the amount of functional protein for this mutation, a greater range of CF individuals could be treated as then the therapy would be suitable for those individuals with the Phe508del-MF mutations.
Next generation CFTR correctors are under evaluation in combination with tezacaftor/ivacaftor. Phase 2 and 3 trials of these triple therapy agents; VX-659 and VX-445 have provided further exciting results. These corrector agents have a different structure and mechanism of action and provide additive function to the other two agents. For individuals homozygous for Phe508del an increase in absolute ppFEV1 was 9.7% for VX-659 treatment and 11% for VX-445 therapy. Greater increases in lung function were seen for patients with Phe508del-MF mutations; the absolute change in ppFEV1 was 13.3 and 13.8% for VX-659 and VX-445 respectively. These increases were also alongside significant improvements in quality of life and have been maintained in subsequent phase 3 interim report analyses [59, 60, 61, 62]. These are incredible outcomes for individuals with more severe mutations and thus who typically have more severe disease phenotypes.
Important advances in the clinical outcomes for individuals with CF have been possible since the introduction of modulator therapy. Unfortunately these treatments are currently associated with a substantial cost and as a result are not available for all eligible patients. In the United States the Food and Drug Administration (FDA) has approved all four of the currently available modulator therapies. Some European countries and Australia, have access to ivacaftor, lumacaftor/ivacaftor and tezacaftor/ivacaftor [63]. However, worldwide there is significant inequality of access to these agents.
As an increasing number of modulator agents become available, the CF community will need to determine how they can enable patients to receive these expensive therapies. If funding bodies are going to approve them, it is likely that they will require significant clinical outcomes from their use, especially when funding is through a public system.
The introduction of modulator therapy, particularly when its use becomes widespread, is likely to have an impact upon the range of CF phenotypes. The amount of phenotypic variations should decrease as fewer patients have significant CFTR channel dysfunctional, and it is likely that the disease manifestations will be less severe. It is well known that respiratory related CF disease is associated with less than 10% CFTR channel function and so there is the potential for modulator therapy to have an impact upon this [21]. However, measurements of the degree of change in CFTR channel functionally with the use of modulator therapy is not being undertaken in the clinical setting. The markers being assessed are all surrogate markers of CFTR channel function and include lung function, sweat chloride, weight and quality of life questionnaires. Hence, it will be interesting to see the long-term impact of significant CFTR modulation on the CF cohort when individuals have been on such treatment for many years from birth. Currently a significant improvement is felt to be an increase in ppFEV1 greater than 10%. Time will tell as to whether such changes have a significant impact upon this long-term multi-system disease.
The advancements in CF care over the last decade have been remarkable. The use of HTS drug discovery programs have been instrumental in enabling the development of the CFTR modulator agents, first the potentiators and subsequently the corrector agents. The fact that such therapies target the underlying consequence of the CFTR mutation has led to exciting clinical outcomes for individuals with certain CFTR mutations because altering the function of the CFTR protein at the molecular level is essential for true disease change to occur. “Genetic medicines” require a significant improvement in their clinical outcomes before they can become a viable option to modulator therapy. They do however have the advantage that they are not specific for individual mutation classes and could be used as treatment for all patients.
The introduction of newer targeted therapies is transforming CF care, although it remains to be seen how these treatments will impact the CF community in the longer term. Nevertheless, a shift is starting to occur whereby treatments are determined based upon an individual’s genetic mutations. It is likely that this will lead to a more personalized model of care and it is hoped a step closer to a cure for this life-limiting disease.
CR – no conflict of interest. TK – Clinical Trial Support and Consultancy fees for Vertex Pharmaceuticals, Inc. JW – Clinical Trial Support and Consultancy fees for Vertex Pharmaceuticals, Inc.
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In this context, this chapter presents key subjects while implementing a quality management system at materials science laboratories and some considerations on strategies for effectively implementing such systems.",book:{id:"5486",slug:"quality-control-and-assurance-an-ancient-greek-term-re-mastered",title:"Quality Control and Assurance",fullTitle:"Quality Control and Assurance - An Ancient Greek Term Re-Mastered"},signatures:"Rodrigo S. Neves, Daniel P. Da Silva, Carlos E. C. Galhardo, Erlon H.\nM. Ferreira, Rafael M. Trommer and Jailton C. Damasceno",authors:[{id:"20571",title:"Prof.",name:"Erlon H.",middleName:null,surname:"Martins Ferreira",slug:"erlon-h.-martins-ferreira",fullName:"Erlon H. Martins Ferreira"},{id:"145815",title:"Dr.",name:"Rodrigo",middleName:null,surname:"De Santis Neves",slug:"rodrigo-de-santis-neves",fullName:"Rodrigo De Santis Neves"},{id:"145816",title:"Dr.",name:"Carlos",middleName:null,surname:"Eduardo Cardoso Galhardo",slug:"carlos-eduardo-cardoso-galhardo",fullName:"Carlos Eduardo Cardoso Galhardo"},{id:"159056",title:"Dr.",name:"Jailton",middleName:null,surname:"Damasceno",slug:"jailton-damasceno",fullName:"Jailton Damasceno"},{id:"191863",title:"Dr.",name:"Daniel",middleName:"Pereira Da Silva",surname:"Fernandes",slug:"daniel-fernandes",fullName:"Daniel Fernandes"},{id:"191865",title:"Dr.",name:"Rafael",middleName:null,surname:"Mello Trommer",slug:"rafael-mello-trommer",fullName:"Rafael Mello Trommer"}]},{id:"53946",title:"The Evolution of Quality Concepts and the Related Quality Management",slug:"the-evolution-of-quality-concepts-and-the-related-quality-management",totalDownloads:4465,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"Enterprises usually adopt some quality practices to control the product quality during the manufacturing process in order to assure the delivery of qualitative good products to customers. The quality practices or quality management systems adopted by industries will further evolve due to the changes of quality concepts as time goes by. This chapter discusses the change of quality concepts and the related revolution of quality management systems in the past century. The quality concepts were gradually changed from the achievement of quality standards, satisfaction of customer needs, and expectations to customer delight. Since merely satisfying customers is not enough to ensure customer loyalty, the enterprises gradually focus on customers’ emotional responses and their delight in order to pursue their loyalty. The emotion of “delight” is composed of “joy” and “surprise,” which can be achieved as the customers’ latent requirements are satisfied. Thus, the concept of “customer delight” and the means to provide the innovative quality so as to meet the unsatisfied customers’ latent needs are elaborated on. Finally, a framework of innovation creation is developed that is based on the mining of customer's latent requirements. This outline will manifest the essential elements of the related operation steps.",book:{id:"5486",slug:"quality-control-and-assurance-an-ancient-greek-term-re-mastered",title:"Quality Control and Assurance",fullTitle:"Quality Control and Assurance - An Ancient Greek Term Re-Mastered"},signatures:"Ching-Chow Yang",authors:[{id:"11862",title:"Prof.",name:"Ching-Chow",middleName:null,surname:"Yang",slug:"ching-chow-yang",fullName:"Ching-Chow Yang"}]},{id:"62915",title:"Advanced Methods of PID Controller Tuning for Specified Performance",slug:"advanced-methods-of-pid-controller-tuning-for-specified-performance",totalDownloads:3528,totalCrossrefCites:12,totalDimensionsCites:18,abstract:"This chapter provides a concise survey, classification and historical perspective of practice-oriented methods for designing proportional-integral-derivative (PID) controllers and autotuners showing the persistent demand for PID tuning algorithms that integrate performance requirements into the tuning algorithm. The proposed frequency-domain PID controller design method guarantees closed-loop performance in terms of commonly used time-domain specifications. One of its major benefits is universal applicability for both slow and fast-controlled plants with unknown mathematical model. Special charts called B-parabolas were developed as a practical design tool that enables consistent and systematic shaping of the closed-loop step response with regard to specified performance and dynamics of the uncertain controlled plant.",book:{id:"6323",slug:"pid-control-for-industrial-processes",title:"PID Control for Industrial Processes",fullTitle:"PID Control for Industrial Processes"},signatures:"Štefan Bucz and Alena Kozáková",authors:[{id:"21933",title:"Ms.",name:"Alena",middleName:null,surname:"Kozakova",slug:"alena-kozakova",fullName:"Alena Kozakova"},{id:"213658",title:"Dr.",name:"Štefan",middleName:null,surname:"Bucz",slug:"stefan-bucz",fullName:"Štefan Bucz"}]},{id:"75699",title:"Data Clustering for Fuzzyfier Value Derivation",slug:"data-clustering-for-fuzzyfier-value-derivation",totalDownloads:302,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The fuzzifier value m is improving significant factor for achieving the accuracy of data. Therefore, in this chapter, various clustering method is introduced with the definition of important values for clustering. To adaptively calculate the appropriate purge value of the gap type −2 fuzzy c-means, two fuzzy values m1 and m2 are provided by extracting information from individual data points using a histogram scheme. Most of the clustering in this chapter automatically obtains determination of m1 and m2 values that depended on existent repeated experiments. Also, in order to increase efficiency on deriving valid fuzzifier value, we introduce the Interval type-2 possibilistic fuzzy C-means (IT2PFCM), as one of advanced fuzzy clustering method to classify a fixed pattern. In Efficient IT2PFCM method, proper fuzzifier values for each data is obtained from an algorithm including histogram analysis and Gaussian Curve Fitting method. Using the extracted information form fuzzifier values, two modified fuzzifier value m1 and m2 are determined. These updated fuzzifier values are used to calculated the new membership values. Determining these updated values improve not only the clustering accuracy rate of the measured sensor data, but also can be used without additional procedure such as data labeling. It is also efficient at monitoring numerous sensors, managing and verifying sensor data obtained in real time such as smart cities.",book:{id:"9976",slug:"fuzzy-systems-theory-and-applications",title:"Fuzzy Systems",fullTitle:"Fuzzy Systems - Theory and Applications"},signatures:"JaeHyuk Cho",authors:[{id:"329648",title:"Prof.",name:"JaeHyuk",middleName:null,surname:"Cho",slug:"jaehyuk-cho",fullName:"JaeHyuk Cho"}]},{id:"39778",title:"GPS and the One-Way Speed of Light",slug:"gps-and-the-one-way-speed-of-light",totalDownloads:3501,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"2387",slug:"new-approach-of-indoor-and-outdoor-localization-systems",title:"New Approach of Indoor and Outdoor Localization Systems",fullTitle:"New Approach of Indoor and Outdoor Localization Systems"},signatures:"Stephan J.G. Gift",authors:[{id:"141106",title:"Prof.",name:"Stephan",middleName:null,surname:"Gift",slug:"stephan-gift",fullName:"Stephan Gift"}]}],onlineFirstChaptersFilter:{topicId:"115",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"77466",title:"Optimization of Model Predictive Control Weights for Control of Permanent Magnet Synchronous Motor by Using the Multi Objective Bees Algorithm",slug:"optimization-of-model-predictive-control-weights-for-control-of-permanent-magnet-synchronous-motor-b",totalDownloads:149,totalDimensionsCites:0,doi:"10.5772/intechopen.98810",abstract:"In this study, the model predictive control (MPC) method was used within the scope of the control of the permanent magnet synchronous motor (PMSM). The strongest aspect of the MPC, the ability to control multiple components with a single function, is also one of the most difficult parts of its design. The fact that each component of the function has different effects requires assigning different weight coefficients to these components. In this study, the Bees Algorithm (BA) is used to determine the weights. Using the multi-objective function in BA, it has been tried to determine the weights that reduce the current values together with the speed error. Three different PI controllers have been designed to compare the MPC method. The coefficients of one of these are tuned with BA. Good Gain Method and Tyreus-Luyben Method were used in the other two. As a result of experimental studies, it has been observed that MPC can control PMSM more smoothly and accurately than PI controllers, with weights optimized with BA. With MPC, PMSM has been controlled with 15% settling time than other controllers and also with no overshoot.",book:{id:"10778",title:"Model-Based Control Engineering - Recent Design and Implementations for Varied Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10778.jpg"},signatures:"Murat Sahin"},{id:"78164",title:"Use of Discrete-Time Forecast Modeling to Enhance Feedback Control and Physically Unrealizable Feedforward Control with Applications",slug:"use-of-discrete-time-forecast-modeling-to-enhance-feedback-control-and-physically-unrealizable-feedf",totalDownloads:75,totalDimensionsCites:0,doi:"10.5772/intechopen.99340",abstract:"When the manipulated variable (MV) has significantly large time delay in changing the control variable (CV), use of the currently measured CV in the feedback error can result in very deficient feedback control (FBC). However, control strategies that use forecast modeling to estimate future CV values and use them in the feedback error have the potential to control as well as a feedback controller with no MV deadtime using the measured value of CV. This work evaluates and compares FBC algorithms using discrete-time forecast modeling when MV has a large deadtime. When a feedforward control (FFC) law results in a physically unrealizable (PU) controller, the common approach is to use approximations to obtain a physically realizable feedforward controller. Using a discrete-time forecast modeling method, this work demonstrates an effective approach for PU FFC. The Smith Predictor is a popular control strategy when CV has measurement deadtime but not MV deadtime. The work demonstrates equivalency of this discrete-time forecast modeling approach to the Smith Predictor FBC approach. Thus, this work demonstrates effectiveness of the discrete-time forecast modeling approach for FBC with MV or DV deadtime and PU FFC.",book:{id:"10778",title:"Model-Based Control Engineering - Recent Design and Implementations for Varied Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10778.jpg"},signatures:"Derrick K. Rollins"}],onlineFirstChaptersTotal:2},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:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.