\r\n
\r\nCoverage included:
\r\n- Preparation NiO catalyst on FeCrAl Subtrate Using Various Technique at Higher Oxidation Process
\r\n- Electrochemical properties of carbon- supported metal nanoparticle prepared by electroplating methods
\r\n- Fabrication of InGaN-Based Vertical Light Emitting Diodes Using Electroplating
\r\n- Integration Of Electrografted Layers for the Metallization of Deep Through Silicon Vias
\r\n- Biomass adsorbent for removal of toxic metal ions from electroplating industry wastewater
\r\n- Resistant fungal biodiversity of electroplating effluent and their metal tolerance index
\r\n- Experimental design and response surface analysis as available tools for statistical modeling and optimization of electrodeposition processes",isbn:null,printIsbn:"978-953-51-0471-1",pdfIsbn:"978-953-51-4991-0",doi:"10.5772/1913",price:119,priceEur:129,priceUsd:155,slug:"electroplating",numberOfPages:178,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"18ec8cf0e50c5e8170a9d0b20af09b7f",bookSignature:"Darwin Sebayang and Sulaiman Bin Haji Hasan",publishedDate:"April 11th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/1455.jpg",numberOfDownloads:24484,numberOfWosCitations:27,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:25,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:61,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 12th 2011",dateEndSecondStepPublish:"May 10th 2011",dateEndThirdStepPublish:"September 14th 2011",dateEndFourthStepPublish:"October 14th 2011",dateEndFifthStepPublish:"February 13th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"92970",title:"Prof.",name:"Darwin",middleName:null,surname:"Sebayang",slug:"darwin-sebayang",fullName:"Darwin Sebayang",profilePictureURL:"https://mts.intechopen.com/storage/users/92970/images/3175_n.jpg",biography:"Dr Darwin Sebayang was graduated from Rheinisch Westfaelische \nTechnische Hochschule Aachen- Germany (RWTH Aachen- Germany) on Light Structure. He is a professor in Faculty of Mechanical and Manufacturing Engineering at the Universiti Tun Hussein Onn Malaysia. The research focuses on light structure, engineering design and advance material and since five years ago he has been active on development of catalytic converter and exploring the application of electroplating of nickel to FeCrAl for catalytic converter.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Tun Hussein Onn University of Malaysia",institutionURL:null,country:{name:"Malaysia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"121404",title:"Prof.",name:"Sulaiman",middleName:null,surname:"Hasan",slug:"sulaiman-hasan",fullName:"Sulaiman Hasan",profilePictureURL:"https://mts.intechopen.com/storage/users/121404/images/system/121404.jpg",biography:"Professor Dr Sulaiman Haji Hasan has been teaching Manufacturing Engineering since 1980. Graduated in Bachelor of Manufacturing Engineering with Honours from the University of Birmingham , England in 1980, then Master in Advanced Manufacturing System and Technology in the University of Liverpool in 1987. In 1993 he pursued his PhD in Mechanical Engineering and Manufacturing at the University Of Birmingham and graduated in 1997. He has been teaching manufacturing in the Universiti Tun Hussein Onn and has also been a Dean for 8 years. He also supervises research and graduates student and also did some consultancy.He has authored and published more than 60 papers in the areas of specialization. He also advised curriculum and course implementation in private higher educational institutions in Manufacturing.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"505",title:"Electrochemistry",slug:"chemistry-physical-chemistry-electrochemistry"}],chapters:[{id:"35381",title:"Preparation of NiO Catalyst on FeCrAl Substrate Using Various Techniques at Higher Oxidation Process",doi:"10.5772/32862",slug:"preparation-of-nio-catalyst-on-fecral-substrate-using-various-techniques-at-higher-oxidation-process",totalDownloads:2823,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:null,signatures:"Darwin Sebayang, Yanuandri Putrasari, Sulaiman Hasan, Mohd Ashraf Othman and Pudji Untoro",downloadPdfUrl:"/chapter/pdf-download/35381",previewPdfUrl:"/chapter/pdf-preview/35381",authors:[{id:"92970",title:"Prof.",name:"Darwin",surname:"Sebayang",slug:"darwin-sebayang",fullName:"Darwin Sebayang"}],corrections:null},{id:"35382",title:"Electrochemical Properties of Carbon-Supported Metal Nanoparticles Prepared by Electroplating Methods",doi:"10.5772/33682",slug:"electrochemical-properties-of-carbon-supported-metal-nanoparticles-prepared-by-electroplating-method",totalDownloads:2480,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Misoon Oh and Seok Kim",downloadPdfUrl:"/chapter/pdf-download/35382",previewPdfUrl:"/chapter/pdf-preview/35382",authors:[{id:"96667",title:"Prof.",name:"Seok",surname:"Kim",slug:"seok-kim",fullName:"Seok Kim"},{id:"127730",title:"BSc.",name:"Misoon",surname:"Oh",slug:"misoon-oh",fullName:"Misoon Oh"}],corrections:null},{id:"35383",title:"Fabrication of InGaN-Based Vertical Light Emitting Diodes Using Electroplating",doi:"10.5772/32855",slug:"fabrication-of-ingan-based-vertical-light-emitting-diodes-using-electroplating",totalDownloads:4960,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Jae-Hoon Lee and Jung-Hee Lee",downloadPdfUrl:"/chapter/pdf-download/35383",previewPdfUrl:"/chapter/pdf-preview/35383",authors:[{id:"92949",title:"Dr.",name:"Jae-Hoon",surname:"Lee",slug:"jae-hoon-lee",fullName:"Jae-Hoon Lee"},{id:"139589",title:"Prof.",name:"Jung-Hee",surname:"Lee",slug:"jung-hee-lee",fullName:"Jung-Hee Lee"}],corrections:null},{id:"35384",title:"Integration of Electrografted Layers for the Metallization of Deep Through Silicon Vias",doi:"10.5772/33948",slug:"integration-of-electrografted-layers-for-the-metallization-of-deep-through-silicon-vias",totalDownloads:3332,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Frederic Raynal",downloadPdfUrl:"/chapter/pdf-download/35384",previewPdfUrl:"/chapter/pdf-preview/35384",authors:[{id:"91843",title:"Dr.",name:"Paulo De Tarso",surname:"Freire",slug:"paulo-de-tarso-freire",fullName:"Paulo De Tarso Freire"},{id:"97913",title:"Prof.",name:"Ronaldo",surname:"Nascimento",slug:"ronaldo-nascimento",fullName:"Ronaldo Nascimento"},{id:"128249",title:"Dr.",name:"Pierre",surname:"Fechine",slug:"pierre-fechine",fullName:"Pierre Fechine"},{id:"128256",title:"Dr.",name:"Francisco",surname:"Sousa",slug:"francisco-sousa",fullName:"Francisco Sousa"},{id:"128257",title:"Dr.",name:"Vicente",surname:"Neto",slug:"vicente-neto",fullName:"Vicente Neto"},{id:"128515",title:"Prof.",name:"Raimundo",surname:"Teixeira",slug:"raimundo-teixeira",fullName:"Raimundo Teixeira"},{id:"128519",title:"Prof.",name:"Marcos",surname:"Araujo-Silva",slug:"marcos-araujo-silva",fullName:"Marcos Araujo-Silva"}],corrections:null},{id:"35385",title:"Biomass Adsorbent for Removal of Toxic Metal Ions From Electroplating Industry Wastewater",doi:"10.5772/32670",slug:"biomass-adsorbent-for-removal-of-toxic-metal-ions-from-electroplating-industry-wastewater",totalDownloads:5371,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:null,signatures:"Ronaldo Ferreira do. 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Senna and Aderval S. Luna",downloadPdfUrl:"/chapter/pdf-download/35387",previewPdfUrl:"/chapter/pdf-preview/35387",authors:[{id:"99593",title:"Dr.",name:"Frederic",surname:"Raynal",slug:"frederic-raynal",fullName:"Frederic Raynal"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"2549",title:"Ion Exchange Technologies",subtitle:null,isOpenForSubmission:!1,hash:"d5d70a346ca433c501e5968f54286740",slug:"ion-exchange-technologies",bookSignature:"Ayben Kilislioğlu",coverURL:"https://cdn.intechopen.com/books/images_new/2549.jpg",editedByType:"Edited by",editors:[{id:"139903",title:"Prof.",name:"Ayben",surname:"Kilislioglu",slug:"ayben-kilislioglu",fullName:"Ayben Kilislioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2282",title:"Atomic Force 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\r\n\tLandmines are weapons developed to be disseminated on the ground, or close beneath the soil, and to explode, because of the contact or proximity of a person or a vehicle. There are different types of landmines and their basic classification depends on the disruptive potential. In principle, all were developed for military purpose to create forbidden zones, where the enemy could not enter into certain zones. The Ottawa Convention prohibits landmines use, manufacture, trade and stockpile, and requests their destruction, as the objectives of the armed forces cannot justify the fall-off in the humanitarian disruption. This Convention is promoted by the United Nations and is ratified by several nations. It is also left aside by other ones and, of course, ignored by the population where guerrilla-like warfare is going on. The landmine risk, thereafter, is a typical problem of the under-developed countries. The landmine problem cannot be solved as the technology-driven issue, and throughout understanding of the background framework is required. To such purpose, the present investigation tries to acknowledge the main conditioning peculiarities to reach factual feasibility through the solution appropriateness. The resort to landmine munitions characterises quite special warfare theatres, where the local socio-political implications have historical motivations. The solutions, on merely technical soundness, will not work unless also the implications are removed or neutralised.
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His research interests are in industrial robotics, distributed generation, power system control, and smart grid.",institutionString:"University of Moratuwa",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Moratuwa",institutionURL:null,country:{name:"Sri Lanka"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"10",title:"Earth and Planetary Sciences",slug:"earth-and-planetary-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270935",firstName:"Rozmari",lastName:"Marijan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270935/images/7974_n.png",email:"rozmari@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Today, mathematics has impacted virtually every area in biology—from evolution (e.g., Fisher\'s Fundamental Theorem of Natural Selection) to biochemistry (e.g., Michaelis‐Menten Kinetics) [1]. But, the impact of biology on mathematics has been just as transformative and biology itself has served to motivate the development of novel mathematics [2].
In the latter part of the twentieth century, both biologists and mathematicians worked to identify and characterize mechanisms to explain a host of fatal neurodegenerative diseases in mammals ranging from scrapie—an infectious diseases observed in sheep—to fatal familial insomnia—a genetic disorder in humans. Initially, much of the focus of these studies centered on first the identification of the infectious agent of these diseases. The discovery of the prion—a proteinaceous infectious particle—originally represented a fundamental contradiction in the central dogma of molecular biology. But today there is increasing acceptance of protein‐only‐inheritance (see Figure 1) not only for mammalian diseases but also for heritable phenotypes in yeast. At present, mammalian prion diseases are untreatable and continued experimental, mathematical and interdisciplinary research offers the promise for identification of regulatory mechanisms and therapeutic targets.
Prion and protein‐only inheritance. The central dogma of molecular biology stipulated that genotype (DNA) encodes phenotype (visible traits). However, prion proteins represent an important departure from this rule where inheritance may arise from proteins alone. Through adopting a stable misfolded conformation (square) a protein can go from harmless to capable of conferring a number of fatal, progressive neurodegenerative diseases.
Prion diseases offer a particularly intriguing biological phenomenon for mathematical analysis because such diseases cover many different systems and time scales. At the level of a population, such as a herd of sheep or population of deer, prion disease can be studied as a classical epidemic model where infections are spread among an initially uninfected (susceptible population). Prion disease can also be studied as a genetic disease whose phenotype is caused by a gain of function mutation in the gene coding for Prp. While the age of disease onset and death appear to be heritable, linking genotype to phenotype remains challenging [3]. Spontaneous prion disease is thought to be nucleation limited, with the formation of a stable minimal size aggregate (nucleus) of misfolded protein serving as the rate‐limiting step in the appearance of prion diseases. All prion diseases are characterized by aggregates of misfolded protein serving as templates to convert normally folded protein and amplifying through fragmentation. As such, many mathematical formulations have focused primarily on the dynamics of the aggregates themselves through modeling either discrete or continuous sizes using ordinary differential equations (ODEs) or partial differential equations (PDEs), respectively. Finally, in order to model the loss or reversal of the prion phenotype in certain experimental systems, prion dynamics are modeled as a stochastic process.
This chapter reviews the application of mathematical models to the study of prions. Our goal is to serve as a tool for both mathematicians and biologists interested in interdisciplinary research in prion disease. We first describe the time before the identification of the prion, when the work of mathematician Griffiths was central to proposing a protein‐only disease process. We next overview mathematical formulations focusing on the dynamics of prion disease through modeling the kinetics protein misfolding and aggregation as well as the coagulation and fragmentation dynamics of the misfolded aggregates themselves. We close by discussing recent advances and ongoing work in mathematical modeling of prions that are serving to further our understanding and motivate experimental studies and present some open questions.
No discussion of prion disease would be complete without discussion of the field prior to the establishment of the prion hypothesis, which stipulates that protein, rather than virus or bacteria, is the infectious agent of the prion disease. Here we give an overview of historical observations linking a variety of diseases in mammals, leading to the formulation of the prion hypothesis by Griffith [4], subsequent experimental validation by Prusiner [5] and discovery of prions in fungi. (For a more complete history of prion diseases refer to any of these reviews [6–10].)
Scrapie is likely the first prion disease to be observed with reports dating back to the 1500s [7, 11]. The first publication describing scrapie appeared in 1759 [12] and because scrapie was reported to be an infectious “distemper” from which sheep could never recover, shepherds of the time were advised to separate any animal observing symptoms from the rest of the flock. Publications at this time discussed and debated possible modes of transmission for this disease; ideas were wide ranging from inbreeding [13], humidity of the sheep pen [14] and even atmospheric events [15]. By the late nineteenth century, it was strongly believed that scrapie was a hereditary disease, but some reports noted spontaneous occurrences leading some to believe there was two forms of scrapie: hereditary and non‐hereditary [7].
In 1913, Sir Steward Stockman published “Scrapie: An Obscure Disease of Sheep” [16], which served as both a historical record of the disease as well as analysis of its symptoms and progression. In particular, he notes that scrapie has a long incubation time of 2–3 years. Research on the method of transmission of scrapie continued and by the early 1960s, it had been established that scrapie could spread through indirect contact between sheep (grazing in a field that had been occupied by an infected herd) [17], could transmit either as an infectious or heritable disease [18], could be transmitted through serum as when a vaccine for another disease (Louping‐ill) was prepared from sheep infected with scrapie [19] and could transmit between species (from sheep to goat [20] and sheep to mouse [21]). In combination, these observations suggested that scrapie did not behave as any previously observed disease‐causing agent.
Scrapie was not the only prion disease studied in the mid‐twentieth century. Around the same time that cross‐species infectivity of scrapie was demonstrated, researchers were studying kuru, a progressive neurodegenerative disease that appeared in Papua New Guinea. The disease was first reported in the scientific literature when anthropologists [22] and pediatricians [23] reported a deadly disease among the Fore people called kuru. The disease had an unusual distribution by sex and age; among children, both male and female could have the disease, but among adults incidence was nearly always limited to females [9]. It was also observed that the pathology of kuru was similar to a Cruzfeld‐Jacob disease, a very rare neurological disorder [24].
Researchers continued to conduct experiments to uncover the method by which scrapie and kuru were transmitted. In 1959, a critical connection was made between these seemingly separate disorders; Hadlow, a veterinarian, attended an exhibit at the Wellcome Medical Museum in London featuring images of neurological tissue from the brains of individuals who died from kuru. He noted the patterns and appearance of damage was extremely similar to what he had seen in scrapie. The similar pathology, combined with the apparent ability of kuru and scrapie diseases to be acquired or hereditary caused him to conjecture that a similar mechanism could be responsible for both diseases and advised researchers to see experiment with transmission of kuru from humans to other mammals (as had been done for scrapie) [25]. Indeed, soon after Hadlow\'s publication it was shown that, like scrapie, kuru could be transmitted to other mammals [26, 27].
While linking diseases such as scrapie, kuru and Cruzfeld‐Jacob was significant in formulating the prion hypothesis, it did not directly address the question of the infectious unit of the disease. In 1966, Alper and colleagues used radiation and filtration experiments on brains from mice scrapie and determined the infectious agent of scrapie appeared to be able to self‐replicate but without a nucleic acid code; they conclude by indicating the scrapie agent “is likely to be of an unusual nature” [28].
In 1967, Griffiths, a mathematician at Bedford College in London took the observations from Alper [28] and Pattison [29] and suggested the infectious agent of scrapie was “probably a protein without nucleic acid” [4]. While precise mathematical formulations were not given, Griffiths used the same type of reasoning that goes into the development of mathematical models to pose three possible mechanisms by which a host‐encoded protein could act as an infectious agent. Namely, he worked within the known rules of the underlying biological processes to pose hypotheses, which could then act to motivate further experimental design. It is precisely this form of interplay between the mathematical and biological sciences that serve to drive discovery.
It is worth noting that Griffith\'s proposed mechanisms for a protein infectious unit involved three distinct biological processes: gene regulation, protein aggregation and immune response. Because his second mechanism is closest to what we believe to be correct today, we postpone its discussion. First, he suggested a process by a gene encoding the prion protein was typically in the “OFF” state. If the prion protein was capable of acting as an inducer to this gene (i.e., turning it “ON”), then the introduction of prion protein would act infectiously by turning the gene “ON” and further production of the protein would maintain the gene in the “ON” state. As such a prion disease could occur spontaneously if the gene were perturbed to the “ON” state in an individual or be acquired through consumption of a protein. His third mechanism was one where the immune response (antibody) was itself equivalent to the foreign body (antigen) and thus prion disease could be the hosts immunity backfiring.
Remarkably, his second proposal quite closely depicts the dynamics of protein aggregation and fragmentation that today we believe was that of protein aggregation and fragmentation. He posed a simple model where proteins could exist as monomer, dimer, trimer and tetramer. Increase in size could occur through monomer addition and tetramers could split into two dimers. If the reaction to create a dimer from two monomers was itself required the catalytic influence of a dimer, the all‐monomer state would persist stably unless a dimer were introduced. Such a system he noted would be capable of self‐propagating as long as there were monomer (which could be produced by the host) and an initial infectious unit (a dimer, trimer, or tetramer).
Griffith\'s proposed “protein‐only” method of disease transmission spurred further experimental studies. Finally, in 1982, Prusiner demonstrated through several distinct lines of evidence (including sensitivity to proteases) that the infectious agent was a protein and coined the term “prion” to mean proteinaceous infectious particle [5]. Not long after, a team of researchers discovered the host gene coding for the prion protein, named PrP for prion protein, in mammals [30].
While mammalian disease was the driving force behind the investigations so far discussed, mammals are not the only organisms that today we know to exhibit protein‐only inheritance. In 1994, Wickner was investigating a heritable phenotype in yeast that did not appear to have a chromosomal determinant, but was associated with an altered form of a yeast protein Ure2p [31]; he proposed that this phenotype could be prion based. Thus, the prion hypothesis could plausibly explain a number of non‐Mendialian phenotypes discovered and studied by Cox [32]. The facility of yeast as an experimental system has spurred the identification of nearly a dozen prion proteins in yeast each of which is linked with a seemingly harmless phenotype [6, 33]. Thus, this opens the possibility that protein‐only inheritance may well have evolved as a regulatory mechanism.
While today there remain some scientists that reject the notion that a host‐encoded protein could be the infectious agent, increasingly sophisticated experimental studies continue to support the prion hypothesis. For example, in 2013 Zhang and colleagues demonstrated that prion diseases could be induced in mammals from recombinant prion protein produced in bacteria [34]. As such, the prion hypothesis has become the accepted view for both mammalian prion diseases and heritable yeast phenotypes.
Today we understand that proteins capable of propagating through a protein‐only mechanism do so by adopting an abnormal folded‐state (conformation) and forming aggregates each of which may act as a template to induce further misfolding among normally folded protein. (Note that we use the term “prion phenotype” to encompass both the concept of mammalian prion disease and harmless prion phenotypes in yeast.) Indeed, there are multiple possible prion phenotypes (in mammals these correspond to distinct incubation periods for disease symptoms) each of which corresponds to a distinct conformation typically called a prion strain. Finally, while all known mammalian prion phenotypes correspond to the same protein PrP, in fungi there are a number of prion proteins each linked to distinct phenotypes [6, 33]. However, as we will detail further, identification of this infectious agent is only the beginning in characterizing these processes.
In this section, we discuss contributions of mathematical modeling in understanding the dynamics associated with prion disease (more generally phenotype). Because prion phenotypes can be either spontaneous or acquired, a distinction is often made between
In Eigen\'s first model, he explores the possibility suggested by Prusiner [38] that heterodimers act to template misfolding. He considers a system with two‐protein species:
The mathematical model resulting from these assumptions consists of two coupled differential equations. Eigen performed steady‐state analysis to determine the possible asymptotic concentrations of each protein species and how the local stability of each depended on the underlying kinetic values. He found two types of asymptotic behavior were possible and the one the system would converge to depended on the ratio of two kinetic parameters: the catalytic conversion rate and the death/decay rate of the prion conformation of the protein. If the death rate exceeded the conversion rate, the asymptotic concentration of prion proteins (type
Eigen\'s second model, considered two mechanisms where the infectious agents were not individual misfolded protein monomers: a cooperative auto‐catalytic mechanism, which generalized his first model and aggregates of misfolded protein, in accordance with a proposed aggregation mechanism from Lansbury [39–41]. These assumptions result in their own—more complicated—sets of differential equations, but as for the previous model, steady‐state analysis revealed important properties of the asymptotic dynamics. Both models exhibited a “threshold” effect, that is, if the concentration of prion protein were low enough, the healthy state was maintained but the introduction of prion protein exceeding a threshold would cause the exponential growth of prion protein. While the results of Eigen\'s work did not definitively detail all necessary steps in the propagation of prion phenotypes, nor did he demonstrate global asymptotic stability of the prion phenotype, his work demonstrated that mathematical modeling—in particular systems of deterministic ODEs—could be used to theoretically interrogate biological hypotheses on prion dynamics. In particular, Eigen\'s analysis demonstrated that “aggregation is necessarily involved” [37] in prion propagation.
In 1998, Nowak and colleagues built upon Eigen\'s seminal work by incorporating additional experimental observations, in particular work demonstrating sensitivity of distinct Prp strains to protease cleavage. Their mathematical framework of prion infection dynamics was based on having prion aggregates act in two ways; first (as in Eigen\'s model) they would template additional misfolding, but now aggregates themselves could increase fragmentation [42]. Because this model forms the basis of most subsequent mathematical models on prion dynamics, we discuss its formulation in some detail. In this mathematical formulation, the state of the system at time
for
where
Nowak and colleagues [42] were also the first to formalize what today is considered to be the standard prion aggregate kinetics, the
Nucleated polymerization model of prion dynamics. This demonstrates the key steps in the nucleated polymerization model (NPM) of prion aggregate dynamics. (The description of the kinetic parameters is in the text.) This model is characterized by prion aggregates below a critical size
Under the previous simplifications on kinetic rates, this changes the resulting moment closure of the infinite system of ODEs to the following three‐dimensional system of ODEs:
In this new formulation the basic reproductive number of a prion aggregate now also depends on the minimal nucleus size
In 1999 Masel, Jensen and Nowak conducted an extensive analysis of the NPM [43]. In particular, they sought to link experimental observations on the time to appearance of prion disease symptoms with the kinetic parameters of the NPM. Among other contributions, Masel and colleagues determined a viable range of minimal nucleus sizes,
In early twenty‐first century, mathematicians continued formalizing the NPM. Prüss and colleagues [45] demonstrated that the prion phenotypes were globally asymptotically stable and not merely locally stable, through deriving a Lyapunov function. Engler et al. [46] analyzed the well‐posedness of the generalization of the NPM where aggregate sizes were continuous, instead of discrete. As such, rather than an infinite system of ordinary differential equations, the system consisted of a single ODE for protein in the normal configuration and a PDE specifying the distribution of aggregate sizes. While this formulation departs from the physically discrete nature of aggregates, in the limit of large aggregate sizes these formalisms are provably equivalent [47] and the use of PDEs permits a wider array of mathematical techniques. Most notably, the continuous relaxation on aggregate sizes has permitted determination of the explicit asymptotic density [44, 46]. (In comparison, the asymptotic density for the aggregate model with discrete aggregate sizes, while first approximated in 2003 by Pöschel et al. [48], was derived only recently by Davis and Sindi and required special functions [49].)
While today mathematical models of prion aggregate dynamics have been formulated under many more general kinetic assumptions (see [47, 50–52] for example) most of these models have been compared to only
One of the earliest models of self‐assembly of particles was proposed by in 1916 by Smoluchowski [59]. He considered the evolution of the density of clusters of discrete particle sizes under the assumption that clusters of any size could join together (coagulation). In 1935, Becker and Döring introduced kinetic equations for a similar process but where clusters could only change in size through monomer addition or removal [60]. More generally, models of particle self‐assembly are distinguished by their associated set of biochemical equations governing the evolution of cluster sizes. As such, the problem of prion nucleus appearance can be framed as: given a set of biochemical equations governing misfolded protein aggregate formation, determine the time it takes for a critical sized nucleus to form [61].
Broadly speaking, two mathematical formulations have been used to describe the time to nucleus formation: deterministic and stochastic. In a deterministic mathematical model, the predictions or model output is always the same for a given input. In such a formulation, the Law of Mass Action is used to convert the set of biochemical equations to a system of ordinary differential equations (ODEs) [62]. For the standard aggregation processes, like the Becker‐Döring process, systems of ODEs have been extensively studied [60, 63, 64]. In these ODEs, the mathematical model output is a continuously varying quantity approximating the concentration or number of aggregates of each possible size. The time to nucleation would then be specified as the time at which the value associated with the critical nucleus size exceeds a threshold value. When the number of total proteins present is large, a deterministic formulation describes the dynamics well; however, when the number of proteins is small, random effects begin to dominate and to capture these effects a stochastic formulation is required [65]. (We note that for
Stochastic mathematical models allow for the possibility of the same input to produce different output. In this case, the state of the system is given not as a deterministic quantity, but a random variable that can take on different values [68]. For example, given a coin with two sides (heads and tails), the number of times a coin must be flipped until heads appears is a random variable; one might attain heads on the first try or require many trials before heads appears. Because the observed output can change, the quantity of interest is not the specific output but rather its properties. To continue our example, we might wish to know either what the
We note that for nucleation problems, we are interested not in the state of our protein molecules at any particular time, but the first‐arrival time of the nucleus. That is, the time at which the first aggregate of minimal stable size appears. Below we refer to misfolded protein aggregates smaller than the critical nucleus as
We will first frame this problem as a continuous‐time stochastic process and then discuss how statistical properties of the first‐arrival time may be computed. (For a detailed discussion of stochastic processes and first arrival times in biological systems, refer to [61, 68].) For simplicity, let us assume that our system consists of a total number of
We use
Stochastic model for prion nucleus appearance. The rate‐limiting step in the appearance of prion phenotypes is thought to be the waiting‐time until the appearance of a nucleus, an aggregate of misfolded prion protein that exceeds a critical size. In a stochastic formulation, the number of prion subunits of each size is tracked in time. As detailed in the text, we are considering a reduced system where the total number of protein molecules (
There are three methods for computing first‐arrival times and their associated moments (mean, variance, etc.) in this stochastic formulation. First, these quantities may be defined directly by analyzing solutions of the chemical master equation (CME). The CME is the first‐order linear differential equation that describes the time‐evolution of the probability of the system to occupy any particular configuration [68, 71–74]. Because the size of the state‐space is exponential in the number of monomers, the CME is computationally intractable for all but very simple systems. Second, computational simulations representing individual realizations of the nucleation process are generated
We note that beyond the mathematical challenges in modeling nucleation there remain many practical challenges. Experimentally, it is typically not possible to separate the spontaneous appearance of a propagon, an initial infectious aggregate, from the prion phenotype itself. Finally, critical events in the underlying biochemical kinetics of nucleus formation in prion disease are unknown. In our formulation above, we described protein subunits, but the protein itself is only capable of aggregating when in a particular conformational state. As such, an accurate predictive model of spontaneous nucleation must also include a model of protein misfolding. While it is clear that particular prion variants (distinct conformations) are favored under particular experimental conditions [81], the connection between nucleus formation and conformation has yet to be fully explored. As such, nucleation remains a challenge on experimental, mathematical and computational fronts.
As described above, a combination of mathematical and experimental studies over the past few decades have led to the formulation of a protein‐only form of inheritance associated with prion phenotypes. We first summarize our present knowledge and then remark on present day studies and challenges that remain in modeling prion disease. Today we believe that prion phenotypes are established through two distinct phases, nucleation and amplification. Once an initial nucleus—prion aggregate above a critical size—is introduced to a host, four steps are required for successful
However, beyond this basic understanding remain many challenges, both mathematical and biological. We briefly outline some open questions in prion biology we believe are amenable to interdisciplinary approaches.
A promising avenue toward finding approaches to manage prion diseases in mammals, might be to more clearly understand the biochemical processes responsible for a number of reversible prion phenotypes in yeast [33]. As was demonstrated by Derdowski et al. [55], a combination of enzyme‐limited fragmentation and aggregate‐size transmission bias appeared to be responsible for the observed natural rates of curing for the [
Further, biological and mathematical researchers should consider mechanisms of curing prion disease through studying mutations in prion proteins, which are known to slow or halt the disease progression. Such mutations are known to exist in mammals [89] and yeast [90].
Many questions remain about prion phenotypes and it is essential once again for scientists with different backgrounds to utilize their disciplinary expertise and methods to address these questions. As we have discussed, two critical points in the history of prion disease came from researchers that were not primarily biologists, namely the mathematician Griffith [4] and the veterinarian Hadlow [25]. If the past is any predictor, future studies in prion phenotypes will continue to benefit from an interdisciplinary approach.
The KV is an organ transiently present in the early embryonic life of the fish to establish internal body laterality [1, 2]. It derives from the dorsal forerunner cells (DFCs), a cluster of cells that migrate together from shield developmental stage until the end of the epiboly stage during zebrafish development. The DFC cluster later forms a lumen, and cilia start to protrude from the cells apically towards the new space. Thus, the KV organ will be formed by only one cell layer surrounding a lumen (Figure 1). The lumen is also progressively filled with fluid as it opens up through a mechanism involving cystic fibrosis transmembrane conductance regulator (CFTR, OMIM-602421), as described before [3, 4, 5]. CFTR is a chloride channel which absence or dysfunction causes cystic fibrosis [6, 7, 8]. As the KV enlarges, the solitary cilium from each KV cell starts to beat, and by ten somite stage (ss), there are on average 80% motile cilia and 20% immotile cilia in a total of 60 cells [9]. Despite it presents different shapes and sizes, the left-right organizer (LRO) has a conserved function among vertebrates, which is to break initial symmetry of embryonic body plans. As detailed below there are still many gaps in the developmental process of left-right (LR) establishment that need to be tested. Due to its genetic amenability and optical transparency, the zebrafish has gained impact in the LR field as one of the best models for testing early LR establishment questions [2, 9, 10, 11, 12, 13, 14, 15]. So far, it is the only animal system where we can manipulate the LRO without damaging or sacrificing the animal, thus letting it develop until organ localization can be visualized [2]. This allows for causal conclusions to be drawn in the same individual fish, which is a powerful advantage in developmental biology.
The zebrafish Kupffer’s vesicle. (A) It is imaged from the dorsal side of the embryo in the tail region from 6 to 14 hours post fertilization (hpf). (B) KV is formed by one layer of monociliated cells. (C) In
Primary ciliary dyskinesia (PCD) is a rare congenital and heterogeneous disorder (OMIM: 244400) with an estimated prevalence of around 1:10 ,000 according to Rubbo and Lucas [16], which is thought to be higher in consanguineous populations [17]. However, other references in the literature consider a much lower prevalence, affecting approximately 1 in 20,000 individuals [18]. It is thought that the correct prevalence of the disease is unknown because many patients remain undiagnosed. PCD is characterized by a deficient mucociliary clearance, which is caused by the lack of motile cilia in the respiratory epithelia, uncoordinated ciliary pattern, or a total lack of ciliary motion giving rise to static cilia. PCD leads to chronic respiratory infections, and the earlier it is diagnosed, the better prognostic the patients will have. Its clinical features usually begin at birth with respiratory distress followed by a wet cough in early childhood and evolve to include bronchiectasis and chronic sinusitis. In the worst scenario, PCD may lead to lung lobectomy [19].
However, PCD is not just a respiratory disease because half of the PCD cases are associated with situs inversus and heterotaxy, and in these latter cases, there is a high correlation with congenital heart disease [16]. Male sterility is common in adults because normal sperm flagella are special motile cilia and in PCD patients may present defective motility. Female ectopic pregnancies have also been reported due to the presence of defective motile cilia lining the fallopian tubes [20]. PCD usually follows an autosomal recessive inheritance pattern [17].
To date, mutations in more than 35 genes were identified to cause PCD. These genes are mainly coding for axonemal proteins that are required for cilia motility or for proteins that are needed for the assembly or transport of axonemal components [18, 21, 22, 23].
Our body is LR asymmetrical. In humans, the heart, spleen, and pancreas are localized on the left, while most of the liver and gallbladder are placed on the right side of our body axis. The fact that patients with immotile cilia presented defects in the location of their internal organs was not obvious to discern and raised many questions in the 1970s.
Bjorn Afzelius, who devoted great interest to this topic, postulated that the existence of an embryonic organ covered by motile ciliated epithelia should explain the laterality defects seen in patients with the immotile cilia syndrome [24]. However, until today the complete molecular mechanism is still to be fully demonstrated.
Previous early experiments on animal models, namely, in mice mutants named
The KV is ventrally positioned deep in the embryo, close to the yolk (Figure 1), but nevertheless it is accessible for live imaging from the dorsal side. This is only possible due to its optical clarity. The embryo is extremely transparent allowing filming the cilia inside the KV in a live intact zebrafish embryo that is simply mounted in soft agarose and embryo medium. This is strikingly different from any other vertebrate model. Mice require extracting the embryos at 7.5 days after coitus from the mother’s uterus, and then dissected embryos are mounted in a medium prior to removal of the Reichert’s membrane that covers the node, to then allow to film the cilia that lay inside the node [26]. In
Zebrafish KV, due to its optical properties for live imaging, has been extremely useful for the study of nodal flow dynamics (Figure 2). How flow forces could trigger the first signals in the KV cells has been intensively explored in this model by our lab, both using experimental and theoretical approaches [2, 31, 32, 33].
Experimental fluid flow measurements and their different readouts. (A) Native particle tracking where each second has a different color to rapidly show where are the slowest regions of flow in the KV. (B) Rayleigh tests were performed considering a null hypothesis of a bias distribution toward a given KV quadrant, and p values are indicated as green numbers. Note that only particles moving at a distance of r > 0.5 from the center of the KVs were considered (r is the normalized distance from the center (r = 0) to the wall (r = 1) of the KV). (C) Rose maps show where flow is stronger in a radial manner. (D) Vector maps denote the actual flow forces in a vectorial manner. (E) Heat maps of flow speed showing detailed regions within each KV. The pseudocolor scale represents flow speed in micrometers
We focused this review on the LR studies that deal with early events that occur in the KV organ. The nature of the signal that is perceived by the KV/node cells is not yet resolved. It can still be mechanical or chemical (or both) as debated for many years, since the first mouse studies [25, 26, 34]. It is now consensual that fluid flow is important, either by its force or by transporting molecules or molecules inside extracellular vesicles [34, 35, 36].
Zebrafish studies on the speed of flow
The KV system has also been used to demonstrate that cilia length impacts greatly on fluid flow speed [31, 37, 38]. Other labs have also contributed to these biophysical characterizations, such as the Amack lab by analyzing the cell shape changes that lead to the dorsal cluster of cilia [13], reported earlier by Kreiling et al. [39]. The Vermot lab by pioneering the studies on KV flow [40] and recently by studying cilia tilt along the 3D KV [12] and its resultant theoretical flow forces. Contradictory interpretations emerged from our lab [9] and Vermot lab [12] concerning the number of immotile cilia in the KV and the consequent ability for the animal to sense flow in a mechanosensory way. This subject needs further experiments to be solved as our labs used different imaging protocols to determine the number of immotile cilia. Another important contribution trying to understand the immediate output of the flow came from the Sun and Bruckner labs, where Yuan et al. have reported asymmetric intracellular calcium transients that seem to be stronger on the left side and become absent upon
In summary, studies in the KV allowed for the biophysical characterization of fluid flow and have shown that disruption of these properties always lead to defective gene expression of
Autosomal dominant polycystic kidney disease (ADPKD) has been reported to affect 1 in 400–1000 newborns worldwide. However, a recent population-based study in European Union puts ADPKD in the group of rare diseases, having an estimated prevalence rate of less than 1 in 2000 individuals [42]. In any case, ADPKD is for sure the most common genetic cause of renal failure [42], representing a major health problem, with an important socioeconomic impact worldwide.
It is caused by mutations in the human genes
The kidney cyst inflation with water and ions and continuous expansion throughout the patient life is assured by an abnormal transepithelial fluid secretion toward their lumen [47]. CFTR plays a central role in the ADPKD cyst inflation [48, 49, 50, 51, 52, 53]. Early in the cystogenesis process, CFTR becomes abnormally activated in ADPKD cyst-lining cells [48, 49, 50, 51, 52, 53]. Supporting the involvement of CFTR in ADPKD cyst inflation, it was shown that the fluid accumulation within cysts involves CFTR-like chloride currents [53] and it is slowed down either through inhibition or knockdown of CFTR [49, 50, 51, 52, 53]. Additionally, a milder renal phenotype was observed in patients affected by both ADPKD and cystic fibrosis [47].
The in vivo mechanisms involved in the abnormal activation of CFTR during kidney cyst inflation are still emerging. It is known that the lack of calcium homeostasis raises the intracellular levels of cAMP in ADPKD cells [47]. As CFTR activation requires its prior cAMP-dependent phosphorylation by PKA [5, 7, 54, 55], it has been suggested that CFTR is a downstream effector of the raised levels of cAMP, in cyst growth [47]. This led to several studies testing drugs targeting renal cAMP production. However, so far only one drug showed an effect in slowing down the enlargement of cysts in adult ADPKD patients, the Tolvaptan [56]. Acting as a vasopressin V2 receptor antagonist, Tolvaptan lowers the intracellular cAMP levels of the cyst-lining cells and, therefore, the CFTR activity [47].
An evidence is growing that renal cyst formation starts in utero and that hypertension in childhood correlated well with disease severity. This is changing the old paradigm that considers ADPKD has a late-onset disease [57]. However, renal cysts still become clinically detectable only in adulthood, when the disease is fully established. The renal volume determination by imaging techniques (ultrasound, CT, and T2-weighted NMR scans) is the available tool to assess the disease progression. Although the majority of patients remain a- or pauci-symptomatic until adulthood, the natural progression of the disease leads to the total destruction of the renal parenchyma by the countless large cysts. Ultimately, about 50% of patients end up requiring renal replacement therapy in their sixth decade of life. The recent approval of Tolvaptan in Japan, Canada, and European Union brought some hope to patients [48]. However, it shows a moderate effect in slowing down the cyst enlargement [56]. Moreover, its side effects include polydipsia, polyuria, nocturia, pollakiuria [56], and significant liver enzyme elevation [58] limiting the eligible patients to those having <50 years, CKD stages 1–3, and rapidly progressing disease [43]. This means that the identification of biomarkers for the early events of ADPKD is an unmet need of the field. These are needed for the early diagnosis of the disease and accurate prediction of renal function decline and may bring novel therapeutic targets for ADPKD.
There is, therefore, an urgent need to investigate the cellular and biochemical pathways involved in kidney cytogenesis with innovative conceptual and methodological approaches. In this review, we will put forward the zebrafish model and its KV as an unconventional but promising organ model to find such biomarkers.
The zebrafish genome presents seven
The combined knockdown of the paralogues
Curly-up tail curvature characteristic of
Additionally, the knockdown of
Although KV does not express
Confocal images for the immunolocalization of Pkd1l1 in KV cells at the 10–11 ss in WT embryos. Pkd1l1 is detected throughout the cells’ cytoplasm and along their cilia. Pkd1l1 is in green and acetylated α-tubulin in red. Scale bars: 10 μm.
In our perspective, a good model to study the in vivo molecular mechanisms involved in the ADPKD cysts inflation should:
Be a fluid-filled vesicle.
Be lined by ciliated cells that must express Pkd2/Pkd1 and CFTR.
Exhibit a physiological fluid flow induced Ca2+-signaling mediated by Pkd2.
Depend on CFTR activity for its lumen inflation.
Allow the easy knockdown of Pkd2/Pkd1 and CFTR.
Allow the easy access to the organ luminal volume.
Above all, the knockdown of PKD1/PKD2 must increase the CFTR-mediated fluid secretion into the lumen, mimicking the ADPKD cyst inflation process.
The KV is neither related to the kidney nor to the renal function. However, as it fulfills the mentioned requirements, a few years ago we proposed the zebrafish KV as a bona fide model organ of the cyst inflation process [1].
As already mentioned, this fluid-filled vesicle organ is lined by monociliated cells [1, 2, 9]. The KV cilia are motile and generate a fluid flow that is essential for the organ function [2, 9]. These are different from the primary cilia of the nephron epithelium or the cilia present in the luminal surface of
The transparency of zebrafish embryos makes the KV of transgenic lines presenting GFP staining in KV-lining cells accessible by confocal live microscopy [1]. These include
KV volume. Confocal live-microscopy scans of the whole KV of 10–11 ss
The most important feature of the model is the fact that on average the knockdown of PKD2 leads to ~1.6 times larger KV volumes than the CFTR activation. Using a pharmacological approach, we showed that the
This model was an important innovation in testing drugs that may modulate the CFTR-dependent KV inflation. We will publish soon our results with Tolvaptan among other drugs. These may give us clues on new drugs that may prevent ADPKD cyst enlargement.
The zebrafish KV offers unique features that allow the proper study of the in vivo molecular mechanisms of both PCD and ADPKD. In the first disease, the KV has already emerged as an ideal system for its uniqueness in allowing to manipulate early genes and physical properties and then following up the LR pattern of the final organs. In the latter disease, it offers an excellent in vivo model for screening compounds and genes that may slow down cyst enlargement through CFTR inhibition.
The work was fully supported by Sociedade Portuguesa de Nefrologia (research grant 2015), iNOVA4Health - UID/Multi/04462/2013 (a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement) and Fundação para a Ciência e Tecnologia (research grant - PTDC/BEX-BID/1411/2014). MRR was supported by national funds through Fundação para a Ciência e Tecnologia, in the context of the celebration of the program contract foreseen in the numbers 4, 5 and 6 of article 23.º of D.L. no. 57/2016 of 29 August, as amended by Law no. 57/2017 of 19 July. Zebrafish used as animal model were reared and maintained in the CEDOC Fish Facility, with the support from the research consortia Congento, co-financed by Lisboa Regional Operational Programme (Lisboa2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and Fundação para a Ciência e Tecnologia under the project LISBOA-01-0145-FEDER-022170.
The authors declare no conflict of interest.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Gabrić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11328",title:"Botulinum Toxin",subtitle:"Recent Topics and Applications",isOpenForSubmission:!1,hash:"7dd05a316001cef143e209eda51387a7",slug:"botulinum-toxin-recent-topics-and-applications",bookSignature:"Suna Sabuncuoglu",coverURL:"https://cdn.intechopen.com/books/images_new/11328.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"270856",title:"Associate Prof.",name:"Suna",middleName:null,surname:"Sabuncuoglu",slug:"suna-sabuncuoglu",fullName:"Suna Sabuncuoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11085",title:"Polycystic Ovary Syndrome",subtitle:"Functional Investigation and Clinical 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Pedro",middleName:null,surname:"García Márquez",slug:"fausto-pedro-garcia-marquez",fullName:"Fausto Pedro García Márquez"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10669",title:"Corrosion",subtitle:"Fundamentals and Protection Mechanisms",isOpenForSubmission:!1,hash:"4a76d54f8a40fc2e7002a8d13fd617c1",slug:"corrosion-fundamentals-and-protection-mechanisms",bookSignature:"Fahmina Zafar, Anujit Ghosal and Eram Sharmin",coverURL:"https://cdn.intechopen.com/books/images_new/10669.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"89672",title:"Dr.",name:"Fahmina",middleName:null,surname:"Zafar",slug:"fahmina-zafar",fullName:"Fahmina Zafar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10677",title:"Advanced Topics of Topology",subtitle:null,isOpenForSubmission:!1,hash:"bf964c52f9e653fac20a7fcab58070e5",slug:"advanced-topics-of-topology",bookSignature:"Francisco Bulnes",coverURL:"https://cdn.intechopen.com/books/images_new/10677.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"92918",title:"Dr.",name:"Francisco",middleName:null,surname:"Bulnes",slug:"francisco-bulnes",fullName:"Francisco Bulnes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11195",title:"Recent Advances in Biometrics",subtitle:null,isOpenForSubmission:!1,hash:"2d32e33e0f499cb5241734bb75dd2a83",slug:"recent-advances-in-biometrics",bookSignature:"Muhammad Sarfraz",coverURL:"https://cdn.intechopen.com/books/images_new/11195.jpg",editedByType:"Edited by",publishedDate:"July 27th 2022",editors:[{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1394",title:"Applied Physics",slug:"applied-physics",parent:{id:"20",title:"Physics",slug:"physics"},numberOfBooks:5,numberOfSeries:0,numberOfAuthorsAndEditors:74,numberOfWosCitations:15,numberOfCrossrefCitations:13,numberOfDimensionsCitations:24,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"1394",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"11002",title:"Colorimetry",subtitle:null,isOpenForSubmission:!1,hash:"4d1a97ef4f3979a9d08d56f8f034dc3c",slug:"colorimetry",bookSignature:"Ashis Kumar Samanta",coverURL:"https://cdn.intechopen.com/books/images_new/11002.jpg",editedByType:"Edited by",editors:[{id:"42763",title:"Prof.",name:"Ashis Kumar",middleName:null,surname:"Samanta",slug:"ashis-kumar-samanta",fullName:"Ashis Kumar Samanta"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10082",title:"Accelerators and Colliders",subtitle:null,isOpenForSubmission:!1,hash:"7774bddf707cc21601de7051625e30b6",slug:"accelerators-and-colliders",bookSignature:"Ozan Artun",coverURL:"https://cdn.intechopen.com/books/images_new/10082.jpg",editedByType:"Edited by",editors:[{id:"255462",title:"Associate Prof.",name:"Ozan",middleName:null,surname:"Artun",slug:"ozan-artun",fullName:"Ozan Artun"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8434",title:"Modern Applications of Electrostatics and Dielectrics",subtitle:null,isOpenForSubmission:!1,hash:"de3cc628456ab823927d4c8b640eee7f",slug:"modern-applications-of-electrostatics-and-dielectrics",bookSignature:"Dengming Xiao and Krishnaswamy Sankaran",coverURL:"https://cdn.intechopen.com/books/images_new/8434.jpg",editedByType:"Edited by",editors:[{id:"18115",title:"Dr.",name:"Dengming",middleName:null,surname:"Xiao",slug:"dengming-xiao",fullName:"Dengming Xiao"}],equalEditorOne:{id:"266293",title:"Dr.",name:"Krishnaswamy",middleName:null,surname:"Sankaran",slug:"krishnaswamy-sankaran",fullName:"Krishnaswamy Sankaran",profilePictureURL:"https://mts.intechopen.com/storage/users/266293/images/system/266293.jpeg",biography:"Dr. Krishnaswamy Sankaran is the Chief Executive Officer of Radical Innovations Group AB, a clean energy and circular economy infrastructure development company based in Finland. He is the winner of the 2020 Mission Innovation Champion Award under the flagship of 24 countries around the world plus European Commission for his pioneering work in Clean Energy and Circular Economy. He is an established industrialist and entrepreneur with several years of demonstrated track record in energy, utilities, infrastructure, manufacturing, and recycling industries. He has served in various operational and leadership roles in industries, the World Economic Forum, and the European Commission in more than sixteen countries and four continents. He is nominated by the Government of Finland for the prestigious 2020 Mission Innovation Champion Award, a global recognition for clean energy innovation (http://mission-innovation.net/)\n\nDr. Sankaran received a doctorate in Engineering Sciences from the Swiss Federal Institute of Technology ETH Zurich, Switzerland, a master’s degree from Karlsruhe Institute of Technology KIT, Germany, and a joint executive master’s degree in Organisational Development and Leadership from Wharton School, Columbia University, INSEAD, and London Business School. He has several years of training in yoga and Advaita Vedanta, an Indian traditional system of philosophy.",institutionString:"Radical Innovations Group - RIG",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9202",title:"Novel Imaging and Spectroscopy",subtitle:null,isOpenForSubmission:!1,hash:"ac4eacbe6141ecaf009845bdaea0c0fa",slug:"novel-imaging-and-spectroscopy",bookSignature:"Jinfeng Yang",coverURL:"https://cdn.intechopen.com/books/images_new/9202.jpg",editedByType:"Edited by",editors:[{id:"263321",title:"Associate Prof.",name:"Jinfeng",middleName:null,surname:"Yang",slug:"jinfeng-yang",fullName:"Jinfeng Yang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6140",title:"Accelerator Physics",subtitle:"Radiation Safety and Applications",isOpenForSubmission:!1,hash:"f68c778ce6d0271e05997c75618cd6b6",slug:"accelerator-physics-radiation-safety-and-applications",bookSignature:"Ishaq Ahmad and Maaza Malek",coverURL:"https://cdn.intechopen.com/books/images_new/6140.jpg",editedByType:"Edited by",editors:[{id:"25524",title:"Prof.",name:"Ishaq",middleName:null,surname:"Ahmad",slug:"ishaq-ahmad",fullName:"Ishaq Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:5,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"69493",doi:"10.5772/intechopen.89029",title:"Diffraction by a Rectangular Hole in a Thick Conducting Screen",slug:"diffraction-by-a-rectangular-hole-in-a-thick-conducting-screen",totalDownloads:787,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"The phenomenon of diffraction by a rectangular hole in a thick conducting screen is investigated for various structural parameters (aperture sizes, aspect ratios, and screen thicknesses) and some incident angles by making use of the exact solution based on the Kobayashi potential (KP) when an electromagnetic (EM) plane wave with any polarization is impinged on the aperture. Since the KP method yields an eigenfunction expansion of the present geometry, the solution satisfies the proper edge condition as well as all the boundary conditions, and therefore we can obtain highly accurate and fast-convergent results. Many numerical results, which are useful for scientists and engineers, are provided for various physical quantities, such as the far-field diffracted pattern, transmission coefficients (normalized transmitted power), and aperture electric field distributions, and by using these numerical results, we examine the convergent property of the KP solution and discuss the effect of the hole size and shape, screen thickness, and incident polarization on the transmission property of the rectangular hole.",book:{id:"9202",slug:"novel-imaging-and-spectroscopy",title:"Novel Imaging and Spectroscopy",fullTitle:"Novel Imaging and Spectroscopy"},signatures:"Hirohide Serizawa",authors:[{id:"301504",title:"Prof.",name:"Hirohide",middleName:null,surname:"Serizawa",slug:"hirohide-serizawa",fullName:"Hirohide Serizawa"}]},{id:"58023",doi:"10.5772/intechopen.71022",title:"X-Ray Diffraction Detects D-Periodic Location of Native Collagen Crosslinks In Situ and Those Resulting from Non- Enzymatic Glycation",slug:"x-ray-diffraction-detects-d-periodic-location-of-native-collagen-crosslinks-in-situ-and-those-result",totalDownloads:1412,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Synchrotron based X-ray diffraction experiments can be highly effective in the study of mammalian connective tissues and related disease. It has been employed here to observe changes in the structure of Extra-Cellular Matrix (ECM), induced in an ex vivo tissue based model of the disease process underlying diabetes. Pathological changes to the structure and organization of the fibrillar collagens within the ECM, such as the formation of non-enzymatic crosslinks in diabetes and normal aging, have been shown to play an important role in the progression of such maladies. However, without direct, quantified and specific knowledge of where in the molecular packing these changes occur, development of therapeutic interventions has been impeded. In vivo, the result of non-enzymatic glycosylation i.e. glycation, is the formation of sugar-mediated crosslinks, aka advanced glycation end-products (AGEs), within the native D-periodic structure of type I collagen. The locations for the formation of these crosslinks have, until now, been inferred from indirect or comparatively low resolution data under conditions likely to induce experimental artifacts. We present here X-ray diffraction derived data, collected from whole hydrated and intact isomorphously derivatized tendons, that indicate the location of both native (existing) and AGE crosslinks in situ of D-periodic fibrillar collagen.",book:{id:"6140",slug:"accelerator-physics-radiation-safety-and-applications",title:"Accelerator Physics",fullTitle:"Accelerator Physics - Radiation Safety and Applications"},signatures:"Rama Sashank Madhurapantula and Joseph P.R.O. Orgel",authors:[{id:"212413",title:"Prof.",name:"Joseph",middleName:null,surname:"Orgel P.R.O.",slug:"joseph-orgel-p.r.o.",fullName:"Joseph Orgel P.R.O."},{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula"}]},{id:"72188",doi:"10.5772/intechopen.92545",title:"Investigation of the Production of Medical Ir-192 Used in Cancer Therapy via Particle Accelerator",slug:"investigation-of-the-production-of-medical-ir-192-used-in-cancer-therapy-via-particle-accelerator",totalDownloads:598,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"To investigate the production of medical Ir-192 radionuclide used in brachytherapy on Os targets in the energy range of Eparticle = 100 → 1 MeV, we calculated the cross-section results for charged particle-induced reactions. The calculation was done via TALYS code and simulated activity and yield of product of each reaction process in the irradiation time of 1 h with constant beam current of 1 μA. The calculated results were compared with experimental data in the literature. Moreover, based on the calculated cross-section data and the mass stopping powers obtained from X-PMSP program, the integral yield results of all the reaction processes to produce Ir-192 on Os targets were presented as a function of incident particle energy. The obtained results were discussed to recommend appropriate reaction processes and targets for the production of Ir-192.",book:{id:"10082",slug:"accelerators-and-colliders",title:"Accelerators and Colliders",fullTitle:"Accelerators and Colliders"},signatures:"Ozan Artun",authors:[{id:"255462",title:"Associate Prof.",name:"Ozan",middleName:null,surname:"Artun",slug:"ozan-artun",fullName:"Ozan Artun"}]},{id:"68360",doi:"10.5772/intechopen.88352",title:"Development of a Corona Discharge Ionizer Utilizing High-Voltage AC Power Supply Driven by PWM Inverter for Highly Efficient Electrostatic Elimination",slug:"development-of-a-corona-discharge-ionizer-utilizing-high-voltage-ac-power-supply-driven-by-pwm-inver",totalDownloads:1295,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"The corona discharge ionizer has been widely used to eliminate electrostatic charges on insulators in a variety of manufacturing industries for the prevention of electrostatic discharge (ESD) problems. High-speed electrostatic elimination is conventionally required for ionizer performance. Because of the high sensitivity of recent electronic devices to ESD damage, an extremely low-offset voltage (ion balance) is required for the performance of electrostatic eliminators. Long-term performance stability is required to maintain the quality of the products, but the short cleaning interval of the unit increases the operating cost. The efficiency is also affected by the waveform of the applied voltage. The optimization of the applied voltage is an important factor in achieving long-term performance stability. In this study, an intermittent pulse voltage AC power supply was developed to achieve a highly efficient electrostatic elimination with long-term stability high-speed electrostatic elimination and an excellent ion balance.",book:{id:"8434",slug:"modern-applications-of-electrostatics-and-dielectrics",title:"Modern Applications of Electrostatics and Dielectrics",fullTitle:"Modern Applications of Electrostatics and Dielectrics"},signatures:"Katsuyuki Takahashi, Koichi Takaki, Isao Hiyoshi, Yosuke Enomoto, Shinichi Yamaguchi and Hidemi Nagata",authors:[{id:"11890",title:"Prof.",name:"Koichi",middleName:null,surname:"Takaki",slug:"koichi-takaki",fullName:"Koichi Takaki"},{id:"211922",title:"Dr.",name:"Katsuyuki",middleName:null,surname:"Takahashi",slug:"katsuyuki-takahashi",fullName:"Katsuyuki Takahashi"},{id:"298263",title:"Dr.",name:"Isao",middleName:null,surname:"Hiyoshi",slug:"isao-hiyoshi",fullName:"Isao Hiyoshi"},{id:"298264",title:"Mr.",name:"Yosuke",middleName:null,surname:"Enomoto",slug:"yosuke-enomoto",fullName:"Yosuke Enomoto"},{id:"298265",title:"Mr.",name:"Shinichi",middleName:null,surname:"Yamaguchi",slug:"shinichi-yamaguchi",fullName:"Shinichi Yamaguchi"},{id:"298266",title:"Mr.",name:"Hidemi",middleName:null,surname:"Nagata",slug:"hidemi-nagata",fullName:"Hidemi Nagata"}]},{id:"71074",doi:"10.5772/intechopen.91056",title:"Electrostatic Friction Displays to Enhance Touchscreen Experience",slug:"electrostatic-friction-displays-to-enhance-touchscreen-experience",totalDownloads:685,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Touchscreens are versatile devices that can display visual content and receive touch input, but they lack the ability to provide programmable tactile feedback. This limitation has been addressed by a few approaches generally called surface haptics technology. This technology modulates the friction between a user’s fingertip and a touchscreen surface to create different tactile sensations when the finger explores the touchscreen. This functionality enables the user to see and feel digital content simultaneously, leading to improved usability and user experiences. One major approach in surface haptics relies on the electrostatic force induced between the finger and an insulating surface on the touchscreen by supplying high AC voltage. The use of AC also induces a vibrational sensation called electrovibration to the user. Electrostatic friction displays require only electrical components and provide uniform friction over the screen. This tactile feedback technology not only allows easy and lightweight integration into touchscreen devices but also provides dynamic, rich, and satisfactory user interfaces. In this chapter, we review the fundamental operation of the electrovibration technology as well as applications have been built upon.",book:{id:"8434",slug:"modern-applications-of-electrostatics-and-dielectrics",title:"Modern Applications of Electrostatics and Dielectrics",fullTitle:"Modern Applications of Electrostatics and Dielectrics"},signatures:"Reza Haghighi Osgouei",authors:[{id:"286114",title:"Dr.",name:"Reza",middleName:null,surname:"Haghighi Osgouei",slug:"reza-haghighi-osgouei",fullName:"Reza Haghighi Osgouei"}]}],mostDownloadedChaptersLast30Days:[{id:"68360",title:"Development of a Corona Discharge Ionizer Utilizing High-Voltage AC Power Supply Driven by PWM Inverter for Highly Efficient Electrostatic Elimination",slug:"development-of-a-corona-discharge-ionizer-utilizing-high-voltage-ac-power-supply-driven-by-pwm-inver",totalDownloads:1282,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"The corona discharge ionizer has been widely used to eliminate electrostatic charges on insulators in a variety of manufacturing industries for the prevention of electrostatic discharge (ESD) problems. High-speed electrostatic elimination is conventionally required for ionizer performance. Because of the high sensitivity of recent electronic devices to ESD damage, an extremely low-offset voltage (ion balance) is required for the performance of electrostatic eliminators. Long-term performance stability is required to maintain the quality of the products, but the short cleaning interval of the unit increases the operating cost. The efficiency is also affected by the waveform of the applied voltage. The optimization of the applied voltage is an important factor in achieving long-term performance stability. In this study, an intermittent pulse voltage AC power supply was developed to achieve a highly efficient electrostatic elimination with long-term stability high-speed electrostatic elimination and an excellent ion balance.",book:{id:"8434",slug:"modern-applications-of-electrostatics-and-dielectrics",title:"Modern Applications of Electrostatics and Dielectrics",fullTitle:"Modern Applications of Electrostatics and Dielectrics"},signatures:"Katsuyuki Takahashi, Koichi Takaki, Isao Hiyoshi, Yosuke Enomoto, Shinichi Yamaguchi and Hidemi Nagata",authors:[{id:"11890",title:"Prof.",name:"Koichi",middleName:null,surname:"Takaki",slug:"koichi-takaki",fullName:"Koichi Takaki"},{id:"211922",title:"Dr.",name:"Katsuyuki",middleName:null,surname:"Takahashi",slug:"katsuyuki-takahashi",fullName:"Katsuyuki Takahashi"},{id:"298263",title:"Dr.",name:"Isao",middleName:null,surname:"Hiyoshi",slug:"isao-hiyoshi",fullName:"Isao Hiyoshi"},{id:"298264",title:"Mr.",name:"Yosuke",middleName:null,surname:"Enomoto",slug:"yosuke-enomoto",fullName:"Yosuke Enomoto"},{id:"298265",title:"Mr.",name:"Shinichi",middleName:null,surname:"Yamaguchi",slug:"shinichi-yamaguchi",fullName:"Shinichi Yamaguchi"},{id:"298266",title:"Mr.",name:"Hidemi",middleName:null,surname:"Nagata",slug:"hidemi-nagata",fullName:"Hidemi Nagata"}]},{id:"71156",title:"Surface Plasmons and Optical Dynamics on Vanadium Dioxide",slug:"surface-plasmons-and-optical-dynamics-on-vanadium-dioxide",totalDownloads:924,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"We report on plasmonic resonances on VO2 nanodot arrays and associated optical dynamics. The plasmon excitations based on electric field interactions lead to red shifts of the plasmon resonances to lower photon energy with increasing nanodot size. The spectral linewidths of plasmon peaks gradually become narrow with increasing nanodot size. This is related to a reduction in plasmon damping with respect to the electronic band structure of VO2. This specific band structure of VO2 affects the optical dynamics of plasmon resonances at the sub-picosecond scale. The optical excitations of VO2 comprise intraband and interband transitions. The existence of plasmon bands induces long-lived lifetimes on decay processes. Intraband transitions in the conduction band (C.B.) play an important role in producing long lifetimes, attributing to free carriers in the C.B. By contrast, interband transitions related to bound electrons contribute to plasmon damping. The dynamic optical responses are closely related to the electronic band structures of VO2.",book:{id:"9202",slug:"novel-imaging-and-spectroscopy",title:"Novel Imaging and Spectroscopy",fullTitle:"Novel Imaging and Spectroscopy"},signatures:"Hiroaki Matsui",authors:[{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui"}]},{id:"69532",title:"Dielectric Analysis Model for Measurement of Soil Moisture Water Content Using Electrical Capacitance Volume Tomography",slug:"dielectric-analysis-model-for-measurement-of-soil-moisture-water-content-using-electrical-capacitanc",totalDownloads:818,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Electromagnetic methods have been widely used in the measurement of the water content of the soil. These methods utilize the permittivity as electrical properties of the soil, to determine the moisture content of the soil. Since the measurements are carried out indirectly, a calibration between permittivity and the water content of the soil is needed. Generally, the calibration method is generated by using an empirical and mixing model. This study presents a proposed model of calibration by using a normalization approach to calibrate the value of the permittivity of the water content of the soil. Then the model was applied using electrical capacitance volume tomography (ECVT) to image soil water content during infiltration of water in a soil column. Granular and silty sand were used as soil material in the experiments. The result showed that the model for measuring moisture water content can be seen in each layer during soil water infiltration in the soil column.",book:{id:"8434",slug:"modern-applications-of-electrostatics-and-dielectrics",title:"Modern Applications of Electrostatics and Dielectrics",fullTitle:"Modern Applications of Electrostatics and Dielectrics"},signatures:"Mukhlisin Muhammad and Saputra Almushfi",authors:[{id:"306980",title:"Prof.",name:"Muhammad",middleName:null,surname:"Mukhlisin",slug:"muhammad-mukhlisin",fullName:"Muhammad Mukhlisin"},{id:"306981",title:"MSc.",name:"Almushfi",middleName:null,surname:"Saputra",slug:"almushfi-saputra",fullName:"Almushfi Saputra"}]},{id:"71074",title:"Electrostatic Friction Displays to Enhance Touchscreen Experience",slug:"electrostatic-friction-displays-to-enhance-touchscreen-experience",totalDownloads:684,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Touchscreens are versatile devices that can display visual content and receive touch input, but they lack the ability to provide programmable tactile feedback. This limitation has been addressed by a few approaches generally called surface haptics technology. This technology modulates the friction between a user’s fingertip and a touchscreen surface to create different tactile sensations when the finger explores the touchscreen. This functionality enables the user to see and feel digital content simultaneously, leading to improved usability and user experiences. One major approach in surface haptics relies on the electrostatic force induced between the finger and an insulating surface on the touchscreen by supplying high AC voltage. The use of AC also induces a vibrational sensation called electrovibration to the user. Electrostatic friction displays require only electrical components and provide uniform friction over the screen. This tactile feedback technology not only allows easy and lightweight integration into touchscreen devices but also provides dynamic, rich, and satisfactory user interfaces. In this chapter, we review the fundamental operation of the electrovibration technology as well as applications have been built upon.",book:{id:"8434",slug:"modern-applications-of-electrostatics-and-dielectrics",title:"Modern Applications of Electrostatics and Dielectrics",fullTitle:"Modern Applications of Electrostatics and Dielectrics"},signatures:"Reza Haghighi Osgouei",authors:[{id:"286114",title:"Dr.",name:"Reza",middleName:null,surname:"Haghighi Osgouei",slug:"reza-haghighi-osgouei",fullName:"Reza Haghighi Osgouei"}]},{id:"69493",title:"Diffraction by a Rectangular Hole in a Thick Conducting Screen",slug:"diffraction-by-a-rectangular-hole-in-a-thick-conducting-screen",totalDownloads:786,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"The phenomenon of diffraction by a rectangular hole in a thick conducting screen is investigated for various structural parameters (aperture sizes, aspect ratios, and screen thicknesses) and some incident angles by making use of the exact solution based on the Kobayashi potential (KP) when an electromagnetic (EM) plane wave with any polarization is impinged on the aperture. Since the KP method yields an eigenfunction expansion of the present geometry, the solution satisfies the proper edge condition as well as all the boundary conditions, and therefore we can obtain highly accurate and fast-convergent results. Many numerical results, which are useful for scientists and engineers, are provided for various physical quantities, such as the far-field diffracted pattern, transmission coefficients (normalized transmitted power), and aperture electric field distributions, and by using these numerical results, we examine the convergent property of the KP solution and discuss the effect of the hole size and shape, screen thickness, and incident polarization on the transmission property of the rectangular hole.",book:{id:"9202",slug:"novel-imaging-and-spectroscopy",title:"Novel Imaging and Spectroscopy",fullTitle:"Novel Imaging and Spectroscopy"},signatures:"Hirohide Serizawa",authors:[{id:"301504",title:"Prof.",name:"Hirohide",middleName:null,surname:"Serizawa",slug:"hirohide-serizawa",fullName:"Hirohide Serizawa"}]}],onlineFirstChaptersFilter:{topicId:"1394",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81712",title:"Atomic Force Microscope in Forensic Examination",slug:"atomic-force-microscope-in-forensic-examination",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.104704",abstract:"Criminal activities have their footprints from time immemorial and nature of crime has drastically changed over a period of time. There is neither a geographical boundary, nor technical limitations. Moreover terrorist’s activities, drug trafficking eco-crimes, high-profile crimes, robbery hit and run cases, building collapse, petroleum products adulteration are some of latest forms of crimes. In last 20 years, scanning probe microscopes have emerged as an essential technique in various fields, and atomic force microscope (AFM) is most commonly used scanning probe technique which has shown its wide range of application in examination of various evidences encountered on crime scene. Major advantages of AFM involve its high resolution in three dimensions, and sample is not necessary to be conductive and it does not need to be operated within a vacuum. It helps in studying a large range of topographies and many types of materials can be imaged under it. Evidences such as blood, fibers, hair, soil, finger prints, gunshot residue, pollen, etc. found on crime scene at nano- or micro-level can be examined under AFM. The chapter describes applications of AFM with respect to its application in examination of evidences that can help in bringing justice.",book:{id:"11146",title:"Electron Microscopy",coverURL:"https://cdn.intechopen.com/books/images_new/11146.jpg"},signatures:"Niha Ansari"},{id:"81935",title:"Laser-Induced Breakdown Spectroscopy and Microscopy Study of Human Dental Tissues",slug:"laser-induced-breakdown-spectroscopy-and-microscopy-study-of-human-dental-tissues",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.105054",abstract:"Laser-induced breakdown spectroscopy (LIBS) analysis of human dental tissues: enamel and dentine, performed by utilizing Nd: YAG laser (????=1064 ????????, ????=6 ????????, ????=50 ????????) to investigate threshold ablation of laser energy density. Quantitative results based on the experiment provide us with threshold ablation value of laser energy density for calcium (Ca) ablation in enamel and dentine tissues. The computed threshold laser energy density for Ca ablation in dentin tissue is 0.38 J/cm2, which is significantly lower than the threshold in the enamel, which is 1.41 J/cm2. Scanning electron microscopic (SEM) examination of dental tissues determines that the dentin surface contains pores, voids, and bubbles that make it easy to ablate at low laser energy density, while enamel has a closely packed smear layer structure that is difficult to ablate, requiring high energy densities. These findings are helpful in the field of laser dentistry, where lasers are widely used for dental treatment.",book:{id:"11146",title:"Electron Microscopy",coverURL:"https://cdn.intechopen.com/books/images_new/11146.jpg"},signatures:"Muhammad Mustafa, Anwar Latif and Majid Jehangir"},{id:"81936",title:"Application of Transmission Electron Microscopy to Detect Changes in Pancreas Physiology",slug:"application-of-transmission-electron-microscopy-to-detect-changes-in-pancreas-physiology",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.104807",abstract:"Insulin resistance in key target organs and beta cell dysfunction due to gluco- and lipotoxicity, are the two main factors driving type 2 diabetes mellitus pathogenesis. Recently, it has been suggested that ectopic fat deposition in the pancreas, named non-alcoholic fatty pancreas disease, occurs in metabolic syndrome, and may play an etiological role in islet dysfunction and damage the exocrine pancreas, increasing its susceptibility to pancreatitis and pancreatic cancer. In this chapter, we present transmission electron microscopy (TEM) as a valuable method to detect early changes in the ultrastructure of pancreatic cells during the development of the metabolic syndrome in mice fed with a western diet (WD). Mice fed with a WD develop pathological ultrastructural alterations in the exocrine and endocrine cells. We demonstrate how to use image segmentation methods and ultrastructural morphometry to analyze and quantify structural changes in cellular organelles and evaluate the presence of lipid droplets, autophagic structures, and vacuolization. Since ultrastructural lesions can be detected early during the progression of the metabolic syndrome, are in many aspects subtle, and by far precede cell apoptosis, necrosis, fat infiltration, and overt functional changes, TEM is not only a suitable but probably the crucial method for detecting early pancreas dysfunction.",book:{id:"11146",title:"Electron Microscopy",coverURL:"https://cdn.intechopen.com/books/images_new/11146.jpg"},signatures:"Maša Skelin Klemen, Jurij Dolenšek, Ismael Valladolid-Acebes, Andraž Stožer and Saška Lipovšek"},{id:"81815",title:"The Cytological Mechanism of Apospory in Paspalum notatum Analyzed by Differential Interference-Contrast Microscopy",slug:"the-cytological-mechanism-of-apospory-in-em-paspalum-notatum-em-analyzed-by-differential-interferenc",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104575",abstract:"Bahia grass (Paspalum notatum Flugge) is an important tropical forage grass and sets seed by apospory. I) To clarify the mechanisms of aposporous embryo sac initial cell (AIC) appearance and apomictic embryo sac formation, and II) to make it clear the mechanism of multiple embryo seed set a development in polyembryonic ovules, several apomictic and sexual varieties of bahia grass were studied cytologically and quantitatively by Nomarski differential interference-contrast microscopy. The results were I) there was no difference between sexual and apomicts to megasporogenesis; and then, the megaspore degenerated in apomicts; at the same time, AIC originated from nucellar tissue appeared and its numbers increased as the ovary grew before anthesis; II) at anthesis, the sac derived from AIC located in the micropylar end (first sac) were 92.5 to 100%, and those in the chalazal ends (other sacs) were 40.4 to 86.0% among the apomicts; the first sac divided dominantly and were 56 to 87% comparable to 0 to 1% of the other sacs at 4 days after anthesis; however, 4 to 17% of the other sacs also showed embryo formations but endosperm. In final, the first sac occupied the whole space of the ovule, in which the embryos in the other sacs coexisted.",book:{id:"11146",title:"Electron Microscopy",coverURL:"https://cdn.intechopen.com/books/images_new/11146.jpg"},signatures:"Lanzhuang Chen and Liming Guan"},{id:"81692",title:"Analysis of Osteoporosis by Electron Microscopy",slug:"analysis-of-osteoporosis-by-electron-microscopy",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.104582",abstract:"Osteoporosis is a skeletal disorder characterized by decreased bone strength which affects the increased risk of fracture. Emerging evidence discovered that osteoporosis is associated with reduced bone density and bone quality. Therefore, analysis of bone morphology can afford insight into the characteristics and processes of osteoporosis. Electron microscopy, one of the best methods, can directly provide ultrastructure evidence for bone morphology. Here, we describe an experimental procedure for electron microscopy preparation and analysis of the resulting images, especially scanning and transmission electron microscopes, to analyze bone morphology in animal models of rats. Compared to other bone analyzers such as atomic absorption spectrophotometer, ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction, scanning and transmission electron microscopes are still important to strengthen visual analysis, and a better understanding of this method could be significant to examine bone morphology.",book:{id:"11146",title:"Electron Microscopy",coverURL:"https://cdn.intechopen.com/books/images_new/11146.jpg"},signatures:"Neng Nenden Mulyaningsih and Rum Sapundani"},{id:"81362",title:"Investigation on Building Materials with the SEM in the ESEM Mode to Demonstrate Their Capillarity Using the Contact Angle Method",slug:"investigation-on-building-materials-with-the-sem-in-the-esem-mode-to-demonstrate-their-capillarity-u",totalDownloads:21,totalDimensionsCites:0,doi:"10.5772/intechopen.104292",abstract:"The chapter describes the use of the Scanning Electron Microscope (SEM) in the Environmental Scanning Electron Microscope (ESEM) mode on building materials, whose capillarity is to be examined. The abbreviation SEM means Scanning Electron Microscope. The abbreviation ESEM means Environmental Scanning Electron Microscope. On the basis of condensation in the ESEM, the hydrophobicity of capillary building materials is demonstrated with the help of the contact angle method. In the chapter, the investigation in the ESEM is shown using capillary building materials that have been given subsequent injections. Due to the problem of rising masonry moisture on capillary masonry in the absence of a cross-section sealing, injection agents, which have a hydrophobic and pore-filling effect, subsequently are used in the borehole method. Such a subsequent masonry sealing must be checked for effectiveness. In addition to already existing macroscopic methods, a new microscopic detection method is presented. This detection method uses ESEM technology in the SEM to generate and detect in situ dew processes at samples taken from the injection level of the examined masonry. The output of the results is done by image or film. By means of the condensation with the medium of water, the contact angle measurement method on the dew drops can be used to make accurate statements about the water-repellent capabilities of the examined sample and thus about the sealing success. There are detectable correlations to the macroscopic detection methods. The contact angles measured in the ESEM during condensation are connected to the conventional macroscopic measurement methods. The method presented in this chapter offers the advantage to have very small samples and to be investigated in a short time with very precise results. The new detection method is suitable for practical use.",book:{id:"11146",title:"Electron Microscopy",coverURL:"https://cdn.intechopen.com/books/images_new/11146.jpg"},signatures:"Peter Körber"}],onlineFirstChaptersTotal:8},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:108,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:140,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:22,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:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{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"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. 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Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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