",isbn:"978-1-80356-465-4",printIsbn:"978-1-80356-464-7",pdfIsbn:"978-1-80356-466-1",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"611776f7f3cc9951a8956d2e3d535a8e",bookSignature:"Associate Prof. Chatchawal Wongchoosuk",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11762.jpg",keywords:"Sensor, Boron Nitride, Energy Applications, Sensing Application, Borophene, 2D Boron Sheet, Boron Nitride Nano-Sheets, BNNS, Boron Carbide, Boron–Carbon Ceramic, B4C, Boron Doping",numberOfDownloads:0,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 2nd 2022",dateEndSecondStepPublish:"May 3rd 2022",dateEndThirdStepPublish:"July 2nd 2022",dateEndFourthStepPublish:"September 20th 2022",dateEndFifthStepPublish:"November 19th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"An expert in the developments of smart sensors and intelligent nanodevices with a wide range of applications, he has received over twenty-eight awards such as TRF–OHEC–SCOPUS Young Researcher Award in physical science, and is listed in the Top 2% World Ranking of Scientists in Electrical & Electronic Engineering in 2020 and 2021 ranked by Stanford University researcher team.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"34521",title:"Associate Prof.",name:"Chatchawal",middleName:null,surname:"Wongchoosuk",slug:"chatchawal-wongchoosuk",fullName:"Chatchawal Wongchoosuk",profilePictureURL:"https://mts.intechopen.com/storage/users/34521/images/system/34521.jpeg",biography:"Chatchawal Wongchoosuk received the Ph.D. and MSc degrees from Mahidol University and the BSc degree with first-class honors in Physics from Prince of Songkla University, Thailand in 2011, 2007, and 2005, respectively. Currently, he is an Associate Professor at Physics Department, Kasetsart University, Thailand. He is a specialist in the development of smart sensors and intelligent systems for food, agricultural and environmental applications. He has received over twenty-eight research awards such as TRF–OHEC–SCOPUS Young Researcher Award in physical science, Invention Award from National Research Council of Thailand, Highest Citation Award for the young researcher, etc. He has served as a reviewer, guest editor, and associate editor for several scientific journals. He is Top 2% World Ranking of Scientists in Electrical & Electronic Engineering in 2020 and 2021 ranked by the Stanford University researcher team. He has published several dozens of articles in reputed journals, proceedings, book chapters, patents, and copyrights. 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1. Introduction
The quest for billets and blooms production in the continuous casting of carbon steels with more stringent quality demands in internal soundness, free from surface defects, and internal porosity has increased the need for more insight in the appraisal of the phenomena associated with solidification under industrial conditions. Medium and high carbon steels cover a broad range of manufacturing products; nevertheless, the production of this type of material with a constant high percentage of prime-choice products remains a tough subject to analyze, understand, and more difficult to attain in practice. These carbon steels exhibit relatively low liquidus and solidus temperatures, with these values decreasing even further as carbon levels increase. It is understood that the blooms produced must be 100% crystallized (solid) at least before cutting to the delivered lengths is accomplished. It is realized that the larger the cross-section of the produced cast product the more time it requires in order to solidify completely. Big-sized cast products (or blooms) are more desirable for mainly two reasons: (a) large cross-sections are associated with large values of mass per unit length, hence, productivity is favored, and more important (b) large cross-sections are subject to larger values of area reduction once rolled, giving products with smaller possibility to quality degradation. On the other hand, the proper control of the cooling intensity in the secondary cooling zones (air-mist spray zones) upon the solidifying product in order to avoid surface/sub-surface defects in the unbending regions of the caster, places limitations on the casting speeds, and therefore productivities are not always at the desired levels. In practice, fundamental operation parameters like casting speed, casting temperature, and cooling-water consumption at the secondary (spray) zones per produced mass of steel are among the most critical ones that the operator should keep in mind, once these have been analyzed, and their impact upon quality has been realized. Furthermore, from the early stages of medium and high-carbon steels casting, the operator has appreciated that it has been impossible to attain the high levels of productivity as with low and medium-low carbon steels without loss of internal quality. This is so because the low solidus temperatures that these grades exhibit become even lower in a dynamic way due to the local cooling rates that affect the solidification mechanism. Indeed, micro-segregation phenomena become more pronounced for these types of steels reducing even further the temperature at which the product becomes 100% solid, or in other terms, the solid fraction becomes one. There are some correlations for the solidus temperatures that unfortunately do not hold appreciably well, under varying cooling conditions, as it normally happens in the industrial continuous casting process. Nevertheless, the liquidus temperature is computed with great precision based upon the liquid-steel chemical analysis, and in this way, the industrial parameter known as superheat, which is the difference between the casting and liquidus temperatures, is calculated correctly; it is known that superheat is of paramount importance in the casting process. In this study, an attempt was carried out in order to shed some light into the effect of the various casting parameters upon the internal quality of the produced blooms in the continuous caster of Stomana, Pernik, Bulgaria. The biggest size of blooms produced currently in this caster is 300 x 250 mm x mm, and most medium and high-carbon grades are produced in this size. A heat transfer and a micro-segregation model were coupled and put into effect in order to facilitate the analysis of solidification along the caster length. Consequently, the solid fraction in the mushy zone, which is actually the intermediate zone between liquid and solid, was computed across a bloom section at any point along the caster, or in other words, from the meniscus level in the mold till the point of analysis. In addition to this, temperature and local-cooling rate distributions were also computed in a similar manner. Different operating conditions were fed into the simulation model in order to compute the required metallurgical lengths, or in other words, the effective cutting lengths that obeyed the unity solid fractions in the mushy zone along the centerline of a bloom.
2. Quality problems associated with internal soundness/central porosity
From the early times of the continuous casting for medium and high carbon steels, it has been realized that central porosity as a quality problem seems inevitable. Figure 1 shows a picture from a macro-etched high carbon bloom cross-section.
Figure 1.
A macro etched cross-section from a 300 x 250 mm x mm bloom. The central porosity, which creates an internal-soundness quality problem, is apparent for this high-carbon cast product.
It is pointed out that for high carbon steels the tendency for central porosity generation is very large no matter how well liquid steel is treated, and how successful the casting process is performed. With time, the continuous casters manufacturers realized that this problem can be abided if electromagnetic stirring (EMS) was applied not only in the mold but in specific positions along the strand, mostly known as strand (S-EMS) and final (F-EMS) positions. F-EMS position is considered the position at which the mushy zone along the centerline becomes solid, or the position around the final solidification of the product. This is an effective technical solution to lessen the problem and is currently applied in some caster installations worldwide. Another promising technical solution is the dynamic soft reduction, in which the part of the bloom which approaches final solidification is subject to a compressive force that slightly reduces its size in one direction but mechanically eliminates the central porosity problem. It is interesting to note that there are installations worldwide that currently apply both technical solutions for internal porosity minimization. However, no matter whether an installation applies one technical solution or another, it is really intriguing to try to figure out why and how this happens, and most importantly up to what extent, depending upon the various casting operating conditions. Without some knowledge upon this problem for a specific installation, one may not appreciate all the phenomena involved in, and maybe a definitive solution may not be successfully attained even after the installation of the discussed technical solutions. That is why it was decided to get some extra information on the subject before the installation of any technical solution might be applied at the Stomana bloom caster.
3. Literature review mostly oriented to quality problems for medium and high carbon steels
Superheat was one of the most fundamental factors recognized from the early years of continuous casting especially for medium and high carbon steels. In an early report [1], pilot plant tests were performed casting 150 x 150 mm x mm billets of high carbon steels. It was proven that at low superheats or even sub-liquidus casting temperatures, the centerline segregation was minimized. The electromagnetic stirring at the mold (M-EMS) exhibited some benefits, and the application of EMS at the strand (S) and final (F) stages of solidification started being installed in some casters worldwide. In a study [2], it was found that the combination of EMS, that is, (S+F)-EMS for blooms and (M+S+F)-EMS for billets, is the most effective method for reducing macro-segregation among various EMS conditions, causing them to solidify more rapidly during the final stages of solidification, providing more finely distributed porosities and segregation spots along the central region. The optimum liquid pool thickness was found to decrease as the carbon content increased, which may be attributed to longer solidification times in the solid fraction range from fs= 0.3 to 0.7. By gaining experience [3] in an actual caster installation, they concluded that a mold tube with a parabolic taper was proven good enough quality-wise for the continuous casting of medium and high carbon steels for carbon contents up to 0.55%. In another study [4], a coupled model was developed consisting of a cellular automaton scheme (CA) simulating the grain structure formation during solidification, and a finite difference scheme simulating the macroscopic heat transfer and solute transport in the continuous casting process. Columnar to equiaxed dendritic transition was effectively reproduced. The effect of superheat on the solidification structure was analyzed, verifying the empirical fact that increasing superheat the columnar dendritic growth increases against the equiaxed one. Under industrial conditions [5], S-EMS applied in the continuous casting of 150 x 150 mm x mm billets reduced centerline segregation up to a degree. However, increasing field intensity, deterioration upon the attained quality improvement was recorded. Some interesting fundamental research, as well as industrial achievements regarding medium and high carbon steels were presented in the recent European continuous casting conference [6-18], revealing the broad research and practice that may be developed in the field during the coming years. In Ref. [6], they used the liquid–solid interface energy as the main property in order to study the micro-segregation during solidification. They concluded that convection effects influenced micro-segregation behavior of the studied high carbon (C ≤ 0.7%), and high manganese steels. In another work [7], a 3D mathematical model was used to analyze the characteristics of magnetic field, flow field, and solidification of molten steel in the mold with electromagnetic stirring for a 260 x 300 mm x mm bloom. A dominant swirling motion at the transverse direction described the flow in the mold; the electromagnetic field was computed with similar values to those measured. They took under consideration the air-gap formation in the corners of the bloom adjacent to the mold. A summary of the actions taken to increase the productivity of Tenaris casters and to ensure high-quality standards in the produced round blooms for low, medium, and high carbon steels was presented in Ref. [8]. An in-house heat transfer model was developed to simulate the temperature distribution at various casting conditions. In addition to this, a rigid-viscoplastic model for simulating the thermal strain effects was developed to assess the potential risk of internal and surface cracks. Industrial practice was improved [9] in the field of high-carbon steel casting by the introduction of EMS not only in the mold, but in specific positions in the strand, and sometimes in the position of the final solidification front. Typical values for solid fraction along the central axis where the F-EMS is effective were found to be in the range of 0.1–0.4. Just for the sake of sense, comparing the findings between the published works [2] and [9] for the valid solid-fraction range for a successful F-EMS application, it is derived that depending upon a specific caster installation different approximations may yield to optimum solutions. In a recent monumental industrial installation [10], the excellent quality results in the production of –among others – medium and high carbon steels were successfully attained by a 2-strand vertical caster (in order to avoid extra strains from the bending/unbending of the strand, which are inevitable to customary curved casters) for the production of big sections of blooms (up to 420 x 530 mm x mm). The caster managed to attain high quality results with the simultaneous application of a soft reduction system plus a moveable F-EMS system per strand. Chaotic phenomena seem to take place [11] in the continuous casting of steel billets, and specifically porosity chains seem to follow chaotic behavior along a cast billet. In other words, the chain of voids that are formed in the central zone along a billet and are generally coupled with segregation exhibit a spacing fluctuation in an erratic, random manner; stochastic modelling was applied on the basis of empirical time series in order to capture much of the dynamics. The lowering of the solidus temperature with respect to carbon-content increase for steels seems to be magnified by the boron effect [12]. Indeed, high Mn medium carbon steels with B higher than 40 ppm exhibit a very low solidification temperature at about 1140°C. In general, it has been verified that for high carbon steels (C≤1%), the addition of B introduces the possibility of a retrograde melting phenomenon retaining liquid at temperatures around 1100°C. In actual practice, a proper secondary cooling scheme should be applied in order to minimize re-melting behavior. In a similar study [13], low and medium carbon boron-steels (B≈30–40 ppm) exhibit a sharp decrease of hot ductility at about 1100°C for a 0.7%Mn content. It was explained on the basis of BN formation after the initial MnS formation; castability is therefore reduced for these types of steels. The implementation of soft reduction at the Voestalpine Stahl Donawitz bloom caster for the continuous casting of high carbon (0.80–1.05%C) rounds exhibited positive quality results [14]. On the other hand, the EMS underlined the proper positioning limitations that made the implementation very difficult to attain reliable and reproducible quality results. Proper design can be successful in as far as quality results are concerned even for small radius casters. In a revamping case [15], good quality results were obtained in a relatively small radius (~5m) caster through multi-radius unbending. Furthermore, the addition of M-EMS, S-EMS, and F-EMS gave rise to the successful casting of medium and high carbon steels with billets cross-sections of 110 x 110 up to 160 x 160 mm x mm. Proper design by reducing roll pitch in the areas where soft reduction was applied and implementing EMS and proper secondary cooling led to the required quality improvements in the revamping of another caster [16] for the production of high carbon steels. The need for fundamental research is illustrated in the following two published works. In the first one [17], an in situ material characterization by bending (IMC-B) 3-point-bending test was developed to simulate crack formation that takes place during continuous casting for most carbon grades; after the test, the strains were calculated using a simulation model in ABAQUS. In the next work [18], it was explicitly verified that micro-segregation phenomena are of paramount importance in the calculation of the final solidification front in order to apply soft reduction efficiently; specifically, an error of about 40°C in the estimation of the solidus temperature may result in an uncertainty of about 1.2 m in the determination of the correct soft reduction point.
4. Micro-segregation effects
The liquidus temperature for a specific steel chemical analysis is calculated with very good accuracy. However, the correct calculation of the solidus temperature is not always that easy. Nevertheless, there are some formulas for the computation of the solidus temperature based upon the specific chemical analysis. One is given by equation (1) as presented in reference [19]:
The Simple model [20] for micro-segregation gives a thorough fundamental analysis for the computation of both the liquidus and solidus temperatures. According to this, the computation of the liquidus temperature is given by equation (2) based on chemical analysis only:
However, for the computation of the solidus temperature the same model [20] requires more computational effort, as the solid fraction in the mushy zone (in which solid and liquid co-exist) depends not only upon temperature but local cooling-rates as well. This can be described as:
fS=G(T,CR)E3
\n\t\t\t
The function G includes the whole logic of calculation depending upon the phase of crystallization, that is, γ, δ, and/or peritectic. Most medium-high and high carbon steels crystallize in the γ phase. Table 1 shows the salient species for the two chemical analyses that were used in this study belonging in the category of medium-high (MC), and high carbon (HC) steels.
Chemical analyses with computed values for the liquidus and solidus temperatures
Equation (2) was used for the calculation of the liquidus temperatures, and equation (1) for the solidus temperature T*S. Nevertheless, in order to have more uniform and comparable results, the solidus temperature TS based on the simple model of micro-segregation analysis was computed at very low cooling rates (10-12 °C/sec) for both steel grades, respectively. Figures 2 and 3 illustrate the effect of micro-segregation upon the solidus temperature and show a form for function G at various levels of cooling rates. It is interesting to note that in both cases, the larger the cooling rate the lower the solidus temperature. On the other hand, the solidus temperatures that were computed by equation (1) are by far above the corresponding values computed by the micro-segregation analysis even at moderate local cooling rates. Furthermore, the biggest difference is computed at the lowest selected cooling rate (10-12 °C/s) for both cases; this extreme low value for the local cooling rate was adopted in order to simulate – as much as possible – the solidus temperature at infinite time of crystallization.
Figure 2.
Micro-segregation results for the selected medium carbon steel at various levels of cooling rates: (T1) CR= 0.01 °C/s, TS = 1394°C; (T2) CR= 0.10 °C/s, TS = 1391°C; (T3) CR= 1.0 °C/s, TS = 1385°C; (T4) CR= 10.0 °C/s, TS = 1379°C.
Figure 3.
Micro-segregation results for the selected high carbon steel at various levels of cooling rates: (T1) CR= 0.01 °C/s, TS = 1313°C; (T2) CR= 0.10 °C/s, TS = 1308°C; (T3) CR= 1.0 °C/s, TS = 1301°C; (T4) CR= 10.0 °C/s, TS = 1292°C.
5. Heat-transfer mathematical approach
The general 3D heat-transfer equation that describes the temperature distribution inside the solidifying body is given by the following equation according to Refs. [21, 22]:
ρCP∂T∂t=∇⋅k∇T+SE4
\n\t\t\t
The source term S may be considered [23] to be of the form:
S=SC+SP⋅TE5
\n\t\t\t
Furthermore, T is the temperature, and ρ, Cp, and k are the density, heat capacity, and thermal conductivity, respectively. The heat transfer equation in Cartesian coordinates may be written as:
ρCP∂T∂t=∂∂x(k∂T∂x)+∂∂y(k∂T∂y)+SE6
\n\t\t\t
The boundary conditions applied in order to solve (6) are as follows.
The heat flux in the mold was computed based on a recent treatment [7] that takes under consideration the air gap formation at the corners of the bloom, in conjunction with another older analysis [24] that came up with more precise heat-transfer coefficients in the mold. In the latter, the heat transfer coefficient at any position inside the mold is given by:
hm,z=1.35⋅10−3(1−0.8z)qmE7
\n\t\t\t
The heat flux at any position in the mold is given by:
qz=a−bz, a=2.680⋅106,b=2.59578⋅106,0≤z≤LmE8
\n\t\t\t
Integrating (8), the average value for heat flux that is transferred through the walls of the mold is:
qm=a−(23b)LmE9
\n\t\t\t
Finally, the mold heat transfer coefficient was adjusted for the air-gap effect at the corners of the bloom [7], according to the following sets of equations:
hm,ag,z=fcorner*hm,zfcorner={1.00≤z≤0.1Lm0.70.1Lm≤z≤0.25Lm for the corner region(†), and 1.0 elsewhere0.5 0.25Lm≤z≤Lm for the corner region(†), and 1.0 elsewhere(†) Corner region: (agWx) along x-axis, (agWy) along the y-axisE10
\n\t\t\t
This formulation reasonably neglects the effect of contact resistance between the solidified shell of steel and the copper mold; this is a valid approach for blooms and big sections generally, as the soft shell bulges a bit and stays in contact with the copper mold in the central areas of the mold, retracting somewhat at the corners. Furthermore, this analysis was performed on similar sized sections (300 x 260 mm x mm) [7]. The heat fluxes due to water spraying and strand radiation in the secondary cooling zones were calculated using the following expressions:
qs=hs⋅(T−Tw0)qr=hr⋅(T−Tenv) with hr=σε⋅T4−Tenv4T−Tenvqc=hc⋅(T−Tenv)E11
\n\t\t\t
where hs, hr, and hc are the heat transfer coefficients for spray cooling, radiation, and convection, respectively, Tw0 is the water temperature, Tenv is the ambient temperature, σ is the Stefan–Boltzmann constant, and ε is the steel emissivity (considered equal to 0.8 in the present study). Natural convection was assumed to be the prevailing convective mechanism, as stagnant air-flow conditions were considered due to the low casting speeds of the strands applied in practice. The strand was assumed to be a long horizontal cylinder with an equivalent diameter of a circle having the same area with that of the cross-section of the bloom, and a correlation valid for a wide Rayleigh number range [25] was applied, written in an appropriate form [26]:
where Nu, Ra, and Pr are the dimensionless Nusselt, Rayleigh, and Prandtl numbers, respectively. In this way, hc is calculated by means of the NuD number. It is worth mentioning, however, that the radiation effects are more pronounced than the convection ones in the continuous casting of steels. From various expressions proposed in the literature for the heat transfer coefficient in water-spray cooling systems, the following formula was applied as approaching the present casting conditions:
hS=1570⋅W0.55⋅1−0.0075Tw04E13
\n\t\t\t
where W is the water flux for any secondary spray zone in liters/m2/sec, and hs is in W/m2/K. At any point along the secondary zones (starting just below the mold) of the caster, the total heat flux qtot is computed according to the following formula, taking into account that qs may be zero at areas where no sprays are present:
qtot=qs+qr+qcE14
\n\t\t\t
In mathematical terms, considering one quarter-section of the bloom assuming symmetry is valid, the aforementioned boundary conditions below mold can be written in compact form:
−k∂T∂x={hm,ag,z(T−TWF) at x=Wx,0≤y≤Wy,0≤z≤Lmqtot at x=Wx,0≤y≤Wy,z>Lm−k∂T∂y={hm,ag,z(T−TWF) at y=Wy,0≤x≤Wx,0≤z≤Lmqtot at y=Wy,0≤x≤Wx,z>LmE15
\n\t\t\t
where z follows the casting direction starting from the meniscus level inside the mold; the mold has an effective length equal to Lm, and Wx and Wy are the half-width (as seen along the horizontal x-axis) and half-thickness (as seen along the vertical y-axis) of the bloom, respectively. Due to symmetry, the heat fluxes across the central planes are considered to be zero:
−k∂T∂x=0 at x=0,0≤y≤Wy,z≥0−k∂T∂y=0 at y=0,0≤x≤Wx,z≥0E16
\n\t\t\t
Finally, the initial temperature of the pouring liquid steel is supposed to be the temperature of liquid steel in the tundish:
T=T0 at t=0(and z=0),0<x<Wx,0<y<WyE17
\n\t\t\t
The thermo-physical properties of carbon steels were obtained from an older published work [27], in which the properties were given as functions of carbon content for the liquid, mushy, solid, and transformation-temperature domain values; this also gave rise to the advantage of eliminating the source factor (S= 0) by absorbing all transformation heats in the heat capacity values.
6. Numerical solution
This specific article is part of a series of published works with respect to the numerical solution of the heat transfer equation in 2D and 3D domains [28-30]. The strongly implicit method as practiced by Patankar [23] was applied. Although a grid of 200 x 200 nodal points was sufficient to stabilize results with a maximum error of 10-2°C for each nodal point in the bloom quarter-section, a final grid of 400 x 400 nodal points was selected for the final computations. The selected time interval (Δt) was 0.25 sec, and the space intervals (Δx, Δy) were about 0.376 mm and 0.313 mm for the horizontal (x-axis) and vertical (y-axis) directions, respectively. Figure 4 depicts the domain (quarter-section) upon which the computations took place. This specific section was also cut in four sub-sections in order to exploit the 4-cores of a professional DELL laptop, Latitude E4310, with 8 GB RAM, operating under Windows 7 Professional. The Gauss–Seidel algorithm for the iterative solution of the matrix of equations was applied, as it was proven as a very suitable scheme for the solution of the temperature distribution putting into effect the OpenMP instruction set for parallel computation. Over-relaxation was applied for the fastest possible convergence; the over-relaxation parameter used was ω= 1.870, which has exhibited good results for these kinds of studies [28-32]. This specific piece of software was developed in GNU C++, version 4.8.1, supplied by TDM-GCC, and accessed through the open source, cross-platform IDE, Code::Blocks, version 13.12. Due to a very large number of data (~2–3 GB) stored in disk per run, a time span of about 30 minutes was required in order to cover the phenomena taking place top-to-bottom in the bloom caster. In summary, the main points of the computations included the following:
Calculation of the temperature distribution inside a bloom cross-section at a specific location at the caster.
Calculation of the local cooling-rates distribution at the same cross-section and position.
Calculation of the solid fraction in the mushy zone at the same cross-section and position.
The dynamic computation of the solidus temperature (at the solid fraction value equal to 1, fs = 1) defined the border of the new solidification front of the mushy zone.
Figure 4.
Illustration of the selected bloom quarter-section for the numerical solution of the 2D heat transfer equation. In roman numerals are depicted the four selected sub-sections upon which each CPU solved the temperature distribution using the Gauss-Seidel algorithm.
In this way, the computed results were stored in the disk and the system proceeded for the next time step; step-by-step the solidification front reached the center of the bloom. In average, about 30–40 iterations per time step sufficed for convergence. The local cooling rates were computed at every nodal point, as follows:
CR=(T|t+Δt−T|t)/ΔtE18
7. Results and discussion
The Stomana bloom caster has a casting radius of 12 m, with M-EMS and no extra EMS or soft reduction along its four strands. Nevertheless, it is interesting to know the effect of critical casting parameters in order to maximize casting speed and hence, productivity, keeping the most attainable good internal porosity as much as possible. Consequently, the effect of parameters like Uc, SPH, ℓpkg, and ag upon LSOL was decided to be analyzed. Preliminary results showed that there were specific ranges of casting speeds Uc depending upon the selected steel grade; moving from MC to HC grades Uc should decrease, otherwise the required casting length for complete solidification LSOL exceeded a lot the design value of the Stomana bloom caster that is close to 34 m. Figures 5 and 6 present typical computational results for the medium and high carbon steel grades selected at specific casting conditions. LSOL values may vary a lot depending upon casting conditions and steel grades. For this reason, a reduced semi-factorial [33] computational experimental design was carried out in order to minimize the steps required to study the phenomenon.
Figure 5.
Casting results for the selected MC grade, for Uc = 0.55 m/min, SPH = 30 K, ℓpkg = 0.200, ag = 12%. (a) Curves 1 and 2 show the centerline and surface temperatures, respectively. (b) Curves 1 and 2 show the shell thicknesses as they progress through the width (x-axis or horizontal direction) and the thickness (y-axis or vertical direction). The solidification or actual metallurgical length computed was 26.12 m. (Run no. 4, Table 2).
Figure 6.
Casting results for the selected HC grade, for Uc = 0.55 m/min, SPH = 30 K, ℓpkg = 0.200, ag = 12%. (a) Curves 1 and 2 show the centerline and surface temperatures, respectively. (b) Curves 1 and 2 show the shell thicknesses as they progress through the width (x-axis or horizontal direction) and the thickness (y-axis or vertical direction). The solidification or actual metallurgical length computed was 35.93 m. (Run no. 3, Table 2).
The adopted values for the casting parameters and the results for the required solidification lengths, for the MC and HC grades selected, are presented in Table 2. Initially it was designed for 12 cases; some more runs were added as of existing preliminary data (included in the statistical analysis).
The effect of air-gap formation upon the temperature distribution in the bloom corners was also verified in this study in accordance with a recent research work published in [7]. Specifically, Figure 7 depicts typical results revealing this important effect. Increasing the percentage of contact loss in the bloom corners due to air-gap formation inside the mold the exit-mold temperatures in the corners increase as well. On the other hand, a statistical analysis that was performed for the effect of the casting conditions upon the required solidification length for the two selected grades as presented in Table 2 showed that the air-gap formation inside the mold has no effect upon LSOL. Probably this may be attributed to the fact that there is a lot of time for temperature re-distribution (soaking) due to conduction during the secondary cooling period, which is long enough as of the low casting speeds applied. Analysis of variance (ANOVA) was carried out using the R statistical package and the overall results are summarized in Table 3. Two things may be pointed out from the results presented in Table 3. First, similar behavior for the effects of the most critical factors upon the solidification length were found; in fact, an increase of 0.05 m/min upon casting speed seems to increase LSOL by 2.4 m for MC, and by 3.2 m for HC, respectively. Similarly, an increase of 10°C upon superheat seems to increase LSOL by 0.72 m for MC, and by 0.52 m for HC, respectively. The specific secondary water-cooling consumption has a negative effect for both grades, but unfortunately it cannot be increased appreciably due to potential surface defects on the blooms. Furthermore, the very good correlations deduced are attributed to the nature of the reduced semi-factorial design of runs that gave the maximum possible information to the ANOVA under the minimum number of tests.
Computational results for the effect of casting speed (Uc), superheat (SPH), specific secondary cooling-water consumption (ℓpkg), and air-gap percentage at the bloom corners (ag) upon the required caster length for complete solidification (LSOL), for the two selected steel grades
Figure 7.
The effect of contact loss between the solidified shell and the mold upon the temperature distribution in the bloom corners, due to air-gap formation in these areas. The presented temperature distributions in the corner regions are from results obtained for MC steel cast at the following conditions: Uc = 0.55 m/min, SPH = 30 K, ℓpkg = 0.200, case (a) ag = 12% (Run no. 4, Table 2), case (b) ag = 0% (Run no. 5, Table 2).
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t
\n\t\t\t\tMC\n\t\t\t
\n\t\t\t
\n\t\t\t\tHC\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tFactor\n\t\t\t
\n\t\t\t
\n\t\t\t\tRegression coefficient\n\t\t\t
\n\t\t\t
\n\t\t\t\tStatistical Significance\n\t\t\t
\n\t\t\t
\n\t\t\t\tRegression coefficient\n\t\t\t
\n\t\t\t
\n\t\t\t\tStatistical Significance\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tUc\n\t\t\t\t\n\t\t\t
\n\t\t\t
47.589
\n\t\t\t
***
\n\t\t\t
64.064
\n\t\t\t
***
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tSPH\n\t\t\t
\n\t\t\t
0.0716
\n\t\t\t
***
\n\t\t\t
0.052
\n\t\t\t
***
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tℓpkg\n\t\t\t
\n\t\t\t
–2.636
\n\t\t\t
***
\n\t\t\t
–2.209
\n\t\t\t
***
\n\t\t
\n\t\t
\n\t\t\t
Intercept
\n\t\t\t
–1.782
\n\t\t\t
***
\n\t\t\t
–0.383
\n\t\t\t
***
\n\t\t
\n\t\t
\n\t\t\t
Correlation coefficient
\n\t\t\t
0.9997
\n\t\t\t
\n\t\t\t
0.9999
\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
Standard error of estimate
\n\t\t\t
0.049
\n\t\t\t
\n\t\t\t
0.0545
\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
F-value
\n\t\t\t
16770, on 3 and 10 DF
\n\t\t\t
\n\t\t\t
26920, on 3 and 9 DF
\n\t\t\t
\n\t\t
\n\t
Table 3.
Linear regression and ANOVA results for the factors affecting the solidification length as performed using R
In this way, a regression formula of the form
Lsol=b0+b1*UC+b2*SPH+b3*ℓpkgE19
\n\t\t\t
is derived, where b’s are the regression coefficients (Table 3) for MC and HC, respectively.
Figure 8.
Casting speeds and productivities per strand in order to have complete solidification along the centerline at the point of cut-to-length products, for the selected MC and HC steels, and at various superheats. MC steel: Curves 1 and 3 represent the casting speed, and productivity for ℓpkg = 0.5, and 2 and 4 similar curves for ℓpkg = 0.2. HC steel: Curves 5 and 7 represent the casting speed and productivity for ℓpkg = 0.5, and 6 and 8 similar curves for ℓpkg = 0.2.
Figure 9.
Typical local cooling-rate results as computed for the selected MC steel cast at the following conditions: Uc = 0.70 m/min, SPH = 30 K, ℓpkg = 0.200, ag = 12% (Run no. 3, Table 2). The results presented correspond to the time instance of 1710 sec, or equivalently, to a position of 19.95 m from the meniscus-level.
More than 99% statistical importance is signified by 3-stars (***) on Table 3, according to R. Figure 8 summarizes the results presented on Table 3 in graphical form. For practical purposes the maximum allowable caster length was considered to be 33 m (instead of 34 m that the Stomana caster actually is), introducing a small safety factor.
Figure 10.
Temperature distribution inside a bloom section as computed for the selected MC steel cast at the following conditions: Uc = 0.70 m/min, SPH = 30 K, ℓpkg = 0.200, ag = 12% (Run no. 3, Table 2). The results presented correspond to the time instance of 1710 sec, or equivalently, to a position of 19.95 m from the meniscus-level. Some solid fraction values are also presented (in purple color).
Figures 9 and 10 illustrate results for the local-cooling rates and temperatures inside a bloom for the MC grade selected, under the same casting conditions at a specific location from the liquid-steel meniscus level in the mold. Figure 9 shows that there is a distribution of local cooling-rate values at any instance inside the bloom. For this case, a simple statistical analysis gave an average value μ = 0.205 °C/s, a standard deviation σ = 0.140, and min and max values equal to 0 and 2.057, respectively. For this average value, the micro-segregation analysis gave a solidus temperature around 1389°C. This value is very close to the solidus temperature of 1387°C that the micro-segregation analysis gave for the computed cooling-rate conditions at the solidification front as depicted in Figure 10. The distances Sx and Sy show the corresponding shell thicknesses along the x and y axes. It is understood that the error would be tremendous if the shell thicknesses were computed based on the a priori solidus temperature (TS*= 1435°C, Table 1) derived upon the chemical analysis only. Similar results are presented in Figures 11 and 12 for the HC grade selected.
Figure 11 depicts the local cooling rates inside a bloom section at about 24.98 m from the liquid steel meniscus level. In this case, the statistical analysis gave an average value for the local cooling rates of μ = 0.204 °C/s, with a standard cooling rate of 0.074, and min and max values of 0 and 1.682, respectively. The local micro-segregation analysis gave a solidus temperature of 1307°C which is shown in Figure 12, and which is very close to the solidus temperature of 1306°C computed from the average cooling-rate of a section at the instance under discussion. One may wonder about the large error upon the estimate of the shell thickness if the whole analysis relied only upon the a priori calculated value (TS* = 1366°C) based on the HC selected chemical analysis – an error of about 60°C in absolute value, erroneously concluding almost 100% solidification at a very premature time!
Figure 11.
Typical local cooling-rates results as computed for the selected HC steel cast at the following conditions: Uc = 0.45 m/min, SPH = 30 K, ℓpkg = 0.200, ag = 6% (Run no. 13, Table 2). The results presented correspond to the time instance of 3330 sec, or equivalently, to a position of 24.98 m from the meniscus-level.
Figure 12.
Temperature distribution inside a bloom section as computed for the selected HC steel cast at the following conditions: Uc = 0.45 m/min, SPH = 30 K, ℓpkg = 0.200, ag = 6% (Run no. 13, Table 2). The results presented correspond to the time instance of 3330 sec, or equivalently, to a position of 24.98 m from the meniscus-level. Some solid fraction values are also presented (in purple color).
Some more results of this nature are presented in Figures 13 and 14 at different casting conditions than those presented in the previous set of data shown in Figures 9 and 10 for the MC steel grade selected. Figure 13 exhibits local cooling rates at an approximate distance of 25 m from the liquid steel meniscus level in the mold. In this case, a short statistical analysis for the local cooling rates gave an average value of μ = 0.264 °C/s, with a standard deviation of 0.087, and min and max values of 0.001 and 1.112, respectively.
Figure 13.
Typical local cooling-rate results as computed for the selected MC steel cast at the following conditions: Uc = 0.55 m/min, SPH = 45 K, ℓpkg = 0.561, ag = 0% (Run no. 7, Table 2). The results presented correspond to the time instance of 2730 sec, or equivalently to an approximate position of 25.0 m from the meniscus-level.
Figure 14.
Temperature distribution inside a bloom section as computed for the selected MC steel cast at the following conditions: Uc = 0.55 m/min, SPH = 45 K, ℓpkg = 0.561, ag = 0% (Run no. 7, Table 2). The results presented correspond to the time instance of 2730 sec, or equivalently to an approximate position of 25.0 m from the meniscus-level. Some solid fraction values are also presented (in purple color).
Figure 14 shows the temperature distribution inside the bloom section at the conditions presented in Figure 13. In this case, the computed solidus temperature at the solidification front was found to be 1389°C, a temperature that also defines the shell thicknesses (Sx and Sy) along the x and y axes.
Figure 15.
Typical local cooling-rate results as computed for the selected HC steel cast at the following conditions: Uc = 0.40 m/min, SPH = 45 K, ℓpkg = 0.200, ag = 0% (Run no. 9, Table 2). The results presented correspond to the time instance of 3750 sec, or equivalently to a position of 25.0 m from the meniscus-level.
Similar results are also presented in Figures 15 and 16 for the HC steel grade selected. At different continuous casting conditions than the ones presented in Figures 11 and 12, these results show data just a couple of meters apart from the final stage of solidification. Figure 15 illustrates in graphical form that the local cooling rates remain as a distribution of values with an average value of μ = 0.230 °C/sec, with a standard error of σ = 0.073, and min and max values of 0 and 1.729, respectively. Figure 16 depicts the temperature distribution inside the bloom section, defining the shell thicknesses along the x and y axes (Sx and Sy), at the computed solidus temperature of 1306°C.
Figure 16.
Temperature distribution inside a bloom section as computed for the selected HC steel cast at the following conditions: Uc = 0.40 m/min, SPH = 45 K, ℓpkg = 0.200, ag = 0% (Run no. 9, Table 2). The results presented correspond to the time instance of 3750 sec, or equivalently to a position of 25.0 m from the meniscus-level. Some solid fraction values are also presented (in purple color).
One last comment about the computed values of local cooling rates: once the shell formation has been created inside the mold, the average values of the local cooling rates are more or less stabilized to specific values. For example, for the cases presented in the Figures 9 through 16, the overall average values for the local cooling rates are about 0.234°C/s for the MC and 0.217°C/s for the HC, respectively. Supplying these values to the micro-segregation model, the values of 1389°C and 1306°C for the solidus temperatures of the MC and HC grades can be deduced, respectively. In this way, a priori calculated values for the solidus temperatures may be used with better precision in heat transfer applications that rely upon preselected values only.
The prediction of the grain size of the solidified metal structure as described in Ref. [27], together with the percentage of the equiaxed zone that may be formed depending on the prevailing heat-transfer conditions may be one part for future work; another part could be the analysis of thermal stress-strain phenomena that act upon the solidifying shell.
8. Conclusions
The installation of strand EMS has been decided for the Stomana caster. The target is to come up with blooms having better internal soundness than the one presented in Figure 1. However, some fundamental points are covered with the help of this study. Summarizing:
The casting conditions with respect to the required casting length for complete solidification have been analyzed, and the effect upon expected productivity per grade is known.
The appreciation of the solidification phenomena is impossible without coupling the micro-segregation analysis, especially for medium and high carbon grades. Once the S-EMS is installed, the specific range of critical solid fractions required for the proper performance of the stirrers can be linked with the operating conditions of the caster.
The difficulty in predicting the solidus temperature at varying cooling conditions especially for high carbon steels has been illustrated. Nevertheless, a shortcut that can generate solidus temperatures to be used as a priori values in heat transfer models has been presented; it only takes some runs for the appropriate heat-transfer models to compute average values for the local cooling rates, which then may be fed to standalone micro-segregation models to calculate the corresponding solidus temperatures. Consequently, simple heat transfer models can simulate casting with less error in the involved solidification phenomena for medium and high carbon steels, by taking as input the solidus temperatures derived in the aforementioned manner.
The great importance of heat transfer analysis on the domain of medium and high carbon solidification is proven once more. It is of paramount importance that mankind has this kind of tool for shedding light into similar type of complex industrial conditions.
Nomenclature
ag; Air gap factor. Percent of the bloom corner that lost contact to mold
Cp; Heat capacity in J kg K-1
fS; Solid fraction
h; Heat transfer coefficient, in W m-2 K-1
k; Thermal conductivity, in W m-1 K-1
L; Length, in m
LSOL; Required caster length for complete solidification, in m
ℓpkg; Specific secondary cooling-water consumption, in liters of water/kg of steel
q; Heat flux, in W m-2
S, Sc; Source term, constant term of S, in W m-3
Sp; Source term that compensates for the temperature dependence of S, in W m-3 K-1
SPH; Superheat, casting temperature – liquidus temperature, in °C or K
t, Δt; Time, time interval, in sec
T; Temperature in a position inside the bloom, or at a nodal point, in °C
TL, TS; Liquidus, solidus temperature, in °C
Uc; Casting speed, in m/min
Wx; Half-width of the bloom, along the (horizontal) x-axis, in m
Wy; Half-thickness of the bloom, along the (vertical) y-axis, in m
x, y, z; Spatial coordinates, in m
Δx, Δy; Distance between adjacent nodal points along the x- and y-axis, respectively, in m
ε; Emissivity
ρ; Density, in kg m-3
σ; The Stefan–Boltzmann constant, which is equal to 5.67 10-8 W m-2 K-4
ω; Over-relaxation factor
Subscripts
0; Referring to an initial value
F, f; Fluid (WF referring to water as cooling fluid)
S, s; Surface, or solid
r, c; Radiation, convection
m; Average value, or referring to the mold
ag; Air gap is considered
Acknowledgments
The author is grateful to the top-management of Sidenor SA for the continuous support upon these types of studies, as well as for the permission of publishing this piece of work. My continuous gratitude and respect to Professor Rabi Baliga from the Mechanical Engineering Department of McGill University, Montreal, Canada, who introduced me to the field of computational fluid-flow and heat transfer should also be acknowledged.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/48505.pdf",chapterXML:"https://mts.intechopen.com/source/xml/48505.xml",downloadPdfUrl:"/chapter/pdf-download/48505",previewPdfUrl:"/chapter/pdf-preview/48505",totalDownloads:2142,totalViews:483,totalCrossrefCites:2,totalDimensionsCites:2,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:71,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"June 12th 2014",dateReviewed:"April 24th 2015",datePrePublished:null,datePublished:"July 29th 2015",dateFinished:"June 5th 2015",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/48505",risUrl:"/chapter/ris/48505",book:{id:"4563",slug:"heat-transfer-studies-and-applications"},signatures:"Panagiotis Sismanis",authors:[{id:"35901",title:"Dr.",name:"Panagiotis",middleName:null,surname:"Sismanis",fullName:"Panagiotis Sismanis",slug:"panagiotis-sismanis",email:"psismanis@sidenor.vionet.gr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Quality problems associated with internal soundness/central porosity",level:"1"},{id:"sec_3",title:"3. Literature review mostly oriented to quality problems for medium and high carbon steels",level:"1"},{id:"sec_4",title:"4. Micro-segregation effects",level:"1"},{id:"sec_5",title:"5. Heat-transfer mathematical approach",level:"1"},{id:"sec_6",title:"6. Numerical solution",level:"1"},{id:"sec_7",title:"7. Results and discussion",level:"1"},{id:"sec_8",title:"8. Conclusions",level:"1"},{id:"sec_9",title:"Nomenclature",level:"1"},{id:"sec_10",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Henderson S., Scholes A., Clarke B.D. Continuous Casting of High-Carbon steels in Billet and Bloom Sections at Sub-Liquidus Temperatures. Technical Steel Research, Final Report, EUR 13623 EN, Belgium, 1991.'},{id:"B2",body:'Oh K.S., Chang Y.W. 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In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 179-188.'},{id:"B9",body:'Sgro A., Rinaldi M., Kunstreich S., Yves D. Recent Danieli Experiences for Electromagnetic Stirrer Optimization in Round Blooms Continuous Casting. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 1454-1461.'},{id:"B10",body:'Sgro A., Rinaldi M., Accardo G. A New Benchmark in Special Steel Casting: New Twin-Strand Vertical Caster at POSCO Specialty Steel, Korea. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 338-346.'},{id:"B11",body:'Tacke K-H. Irregular and Fluctuating Phenomena in Continuous Casting. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 699-708.'},{id:"B12",body:'Alvarez de Toledo G., Komenda J., Stewart B., Brune T., Frisk K. Influence of Composition and Continuous Casting Parameters on the Cracking of B-Micro-alloyed High Mn Steel Grades. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 709-718.'},{id:"B13",body:'Brune T., Haberl F., Senk D. Hot-Ductility and Precipitation Behavior of Boron in Nb-V-Ti Micro-alloyed Steels for CC. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 719-728.'},{id:"B14",body:'Rauter W., Reiter J., Srienc K., Brandl W., Erker M., Huemer K., Mair A. Soft Reduction at a Round Bloom Caster: Implementation and Results. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 811-820.'},{id:"B15",body:'Angelini L., Guerra F., Persi C., Straffelini G., Botelho P. Quality Improvement of the Acciaierrie di Calvisano CCM through the EM Multi-Stirring Technology: Preliminary Results. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 821-830.'},{id:"B16",body:'Chen M-H., Lu C-Y., Lin K-J., Kao C-L., Huang S-Y., Tsai M-F., Kuo A-N. Central Segregation Improvement of High Carbon Steels at CSC #3 Bloom Caster. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 831-838.'},{id:"B17",body:'Krajewski P., Krobath R., Bernhard C., Miettinen J., Louhenkilpi S., Ilie S., Schaden T. A Novel Approach for the Simulation of Surface Cracks Formation in Continuous Casting. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 1160-1169.'},{id:"B18",body:'Hahn S., Schaden T. DynaPhase: Online Calculation of Thermodynamic Properties during Continuous Casting. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 1170-1180.'},{id:"B19",body:'Thomas B.G., Samarasekera I.V., Brimacombe J.K. Mathematical Modeling of the Thermal Processing of Steel Ingots: Part I. Heat Flow Model. Metallurgical Transactions B, Vol. 18B, 1987, pp. 119-130.'},{id:"B20",body:'Won Y-M., Thomas B.G. Simple Model of Micro-segregation During Solidification of Steels. Metallurgical Transactions A, Vol. 32A, 2001, pp. 1755-1767.'},{id:"B21",body:'Carslaw H.S., Jaeger J.C. Conduction of Heat in Solids. Oxford University Press, New York, 1986.'},{id:"B22",body:'Incropera F.P., DeWitt D.P. Fundamentals of Heat Transfer. John Wiley & Sons, New York, 1981.'},{id:"B23",body:'Patankar S.V. Numerical Heat Transfer and Fluid Flow. Hemisphere Publishing Corporation, Washington, 1980.'},{id:"B24",body:'Yoon U-S., Bang I-W., Rhee J-H., Kim S-Y., Lee J-D., Oh K-H. Analysis of Mold Level Hunching by Unsteady Bulging during Thin Slab Casting. ISIJ International, Vol. 42, No.10, 2002, pp. 1103-1111.'},{id:"B25",body:'Churchill S.W., Chu H.H.S. Correlating Equations for Laminar and Turbulent Free Convection from a Horizontal Cylinder. Int. J. Heat Mass Transfer, Vol.18, 1975, pp. 1049-1053.'},{id:"B26",body:'Burmeister L.C. Convective Heat Transfer. John Wiley & Sons, 1983, p. 551.'},{id:"B27",body:'Cabrera-Marrero J.M., Carreno-Galindo V., Morales R.D., Chavez-Alcala F. Macro-Micro Modeling of the Dendritic Microstructure of Steel Billets by Continuous Casting. ISIJ International, Vol. 38, No. 8, 1998, pp. 812-821.'},{id:"B28",body:'Sismanis P. Heat Transfer Analysis of Special Reinforced NSC-Columns under Severe Fire Conditions. International Journal of Materials Research, Vol. 101, March 2010, DOI 10.3139/146.110290, pp. 417-430.'},{id:"B29",body:'Sismanis P. Modeling Solidification Phenomena in the Continuous Casting of Carbon Steels. In: Amimul Ahsan (ed.). Two Phase Flow, Phase Change and Numerical Modeling. Rijeka: InTech; 2011. p.121-148. Available from by http://www.intechopen.com/books/two-phase-flow-phase-change-and-numerical-modeling/modeling-solidification-phenomena-in-the-continuous-casting-of-carbon-steels (accessed 21 August 2014).'},{id:"B30",body:'Sismanis P. The Effect of Local Cooling Rates upon Solidification Phenomena in the Continuous Casting of Carbon Steels. In: 8th European Continuous Casting Conference and Symposium in Numerical & Physical Modeling, ASMET, 23-26 June 2014, Graz, Austria, pp. 1462-1471.'},{id:"B31",body:'Anderson D.A., Tannehill J.C., Pletcher R.H. Computational Fluid Mechanics and Heat Transfer. Hemisphere Publishing Corporation. Washington. 1984.'},{id:"B32",body:'James M., Smith G.M., Wolford J.C. Applied Numerical Methods for Digital Computation with FORTRAN and CSMP. Harper & Row Publishers. New York. 1977.'},{id:"B33",body:'Montgomery D.C. Design and Analysis of Experiments. 2nd ed., John Wiley, New York, 1984.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Panagiotis Sismanis",address:"psismanis@sidenor.vionet.gr",affiliation:'
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1. Introduction
Skin is the largest organ of human organism, approximately 2m2. This envelop, in constant contact with the environment, can be divided into three layers: a deep layer, the hypodermis; then an intermediate layer, the dermis; and finally, a superficial layer, the epidermis. This top layer is mainly constituted of keratinocytes, which form the first physical and chemical barrier between the external environment and our body. To maintain this function, keratinocytes undergo a multistep process of differentiation, from proliferating cells of the stratum basale to stratum spinosum (mature basal cells linked by keratin filaments – desmosomes), granulosum (mature keratinocytes, which generate keratin and keratohyalin granules), and lucidum (dead and flattened cells), to finally generate dead cornified corneocytes found in stratum corneum [1, 2]. These highly differentiated cells, devoid of nucleus and organelles, form the cornified envelop and are essential for the skin barrier function.
Despite its major keratinocyte content, epidermis is also composed of other cell populations in order to ensure protection of our organisms [1, 2]. Its immunity is guaranteed by Langerhans cells, a dendritic cell that contributes to innate and adaptative immunity [1, 2]. The sensory nerve endings passing through the epidermis (C-fibers and Aδ-fibers) were thought to be the exclusive transducers for the detection of environmental factors such as heat and pain, but Merkel cells can also act as mechanosensors [3]. Free intra-epidermal sensory nerve endings are all unmyelinated: C-fibers are unmyelinated, while Aδ-fibers lose their myelination when they enter the epidermis, allowing them to come into direct contact with the epidermal keratinocytes (Figure 1A) [4]. Therefore, in addition to the intra-epidermal sensory nerve endings, the epidermal keratinocytes also function as a sensory hub, able to detect environmental changes [5, 6]. Finally, the epidermis is constituted by another cell population: the melanocytes, located in the basal layer. With one for 4–10 keratinocytes, melanocytes provide a barrier from ultraviolet (UV) thanks to their ability to produce melanin, a photoprotector pigment [1, 2]. Opposite to the epidermis, the dermis is mainly composed of extracellular matrix produced by dermal fibroblasts. This intermediate layer also supports dermal blood vessels, nerve fibers, and epidermal appendages (pilosebaceous unit and sweat glands). Finally, hypodermis is composed of adipocytes separated by connective tissue. This deep layer insulates and protects the skin from mechanical injuries [1, 2]. Thus, the skin allows a protection against externals insults (ultraviolet, pathogens, mechanical pressure, etc.…) but also contributes to the maintenance of homeostasis such as information transfer, vitamin and metabolites secretions, hydric and thermal regulation.
Figure 1.
Schematic representation of skin and TRPV1/TRPV3 location. A. Skin structure. Skin and its three layers: epidermis, dermis, and hypodermis. Nerve fibers are present in the epidermis or in the dermis depending on their properties and their type. Two major groups of skin nerve fibers are represented: Aδ fibers (green) poorly myelinated and able to pass through the dermo-epidermal junction, and Aβ fibers (yellow) strongly myelinated and not able to reach the epidermis. C-fibers are unmyelinated and able to pass through the dermo-epidermal junction. B. TRPV1 and TRPV3 location. TRPV1 is expressed in various cell types with a dominance in keratinocytes and sensory nerves (C fibers). TRPV3 expression is restricted to keratinocytes with a putative expression on sensory nerves.
To cope with various externals constrains, various cells of the skin express transmembrane sensors called Transient Receptor Potential (TRP) channels, which are involved in thermosensation, chemosensation, nociception, and mechanosensation [7]. TRP channels can be divided into six subfamilies: TRPA (ankyrin), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPV (vanilloid). Although TRPV channels have a major role in thermosensation [8], they also contribute to keratinocyte differentiation, skin barrier formation, and permeability thanks to calcium regulation. However, it appears that an aberrant TRP channel expression and function might contribute to some skin inflammatory diseases. In this review, we will focus on TRPV1 and TRPV3 structures, activation mechanisms, and their physiological roles in skin. We will also provide a new approach to study TRPV1 and TRPV3 channels in a very common chronic inflammatory disease, such as psoriasis.
2. TRPV1 and TRPV3 structure and gating
2.1 Expression and genetics
Among the six members of TRPV channels, thermosensors TRPV1 and TRPV3 are calcium channel both highly expressed in the skin, with different cells types expression (Figure 1B). The TRPV1 channel was firstly described on nociceptive sensory nerves from Dorsal Root sensory Ganglia (DRG) by Caterina et al in 1997 [9]. TRPV1 was detected on a subset of skin sensory nerves, such as peptidergic and non-peptidergic C fibers. Different studies have also proposed TRPV1 channel to be expressed on non-neuronal skin cells population. Indeed TRPV1 is expressed in human and mouse skin as TRPV1 immunoreactivity has been observed on Langerhans cells, mast cells, endothelium, and smooth muscle cells from dermal blood vessels, differentiated sebocytes, sweat glands, hair follicles (inner root and infundibulum), and finally on keratinocytes [10, 11, 12].
Unlike TRPV1, TRPV3 channels tissue expression is more restricted. Peier et al. (2002) have demonstrated the expression of Trpv3 in the skin, with a strong immunodetection on keratinocytes from epidermis and hair of rat [13]. We also confirmed a higher TRPV3 expression in cultured human primary keratinocytes as compared with TRPV1 (5.5-fold change, unpublished data). In contrast, TRPV3 expression and activity on sensory nerves are still controversial. Indeed, TRPV3 mRNA was detected on sensory neuron in DRG and trigeminal ganglia of monkey [14], while others have reported an absence of Trpv3 activity on mouse DRG, and then suggested no expression on these cells [15]. Finally, another group has proposed a heterodimeric form TRPV1-TRPV3 on sensory neurons [16]. Even if TRPV3 expression on sensory nerves is not completely clear, it is believed that epidermal TRPV3 and sensory nerves are able to communicate via chemical mediators. Indeed, TRPV3 activation in keratinocytes causes the secretion of an array of signaling factors, such as Nerve Growth Factor (NGF), Nitric Oxide (NO), Prostaglandin E2 (PGE2), and Adenosine-Triphosphate (ATP).
TRPV1 (chr17:3,565,446-3,609,411) and TRPV3 (chr17:3,513,190-3,557,805) genes exist in tandem on human chromosome 17, with the same transcriptional orientation and are distant from less than 7650 base pairs, indicative of an ancestral gene duplication. In humans, the TRPV1 gene spans 17 exons encoding an 839 amino acids (aa) protein. Alternative splicing may occur and give rise to a modified amino acids sequence in the first 150 residues. The TRPV3 gene spans 18 exons encoding a prevalent isoform of 790 amino acids. As for TRPV1, TRPV3 might be differentially spliced, yielding two additional isoforms of 791 (additional A in position 760) and 765 amino acids (peptide sequence at 760–765 modified from DFNKIQ to GTVAVR together with deletion of residues 766–790). The most prevalent forms of TRPV3 (790 aa) and TRPV1 (839 aa) share 43% sequence homology.
2.2 Common features
The TRP superfamily is the second largest class of ions channels with a voltage-dependent activation mechanism. However, TRP members not only respond to electric signal but are also able to sense several environmental stimuli, rendering them polymodal sensors of the environment. These channels share a highly conserved protein architecture and require a tetrameric assembly to generate a functional central cation permeation pore. Apart from this ion channel pore, different subdomains of the TRPV proteins are responsible for their ability to be responsive to various environmental signals. Each subunit of the tetrameric complex is composed of six transmembrane segments (S1–S6), with the cation permeable pore formed by a reentrant loop located between S5 and S6 (Figure 2). The S1–S4 bundle likely forms the voltage sensor module, although TRPV1 and TRPV3 exhibit a weak voltage dependence for gating. This relatively low capacity of TRPV channels to respond to electric current may be due to the scarcity of positively charged amino acids in the S4 domain that contains a single arginine residue [17, 18]. The large cytoplasmic N-terminal part of a monomer comprises six ankyrin repeats, each consisting of a 33-residue motif forming two antiparallel alpha helices separated by loops linking the adjacent repeats. The ankyrin repeat domains (ARDs) are highly conserved in TRPV1 and TRPV3. The C-terminal part is also a large intracellular region containing a TRP-domain, another highly conserved distinctive and fundamental feature of TRP channels, consisting of a 25 amino acids α-helix structure with a conserved sequence IWKLQR called the TRP box. This TRP domain is running parallel to the inner plasma membrane and intimately lodged within the intracellular side of the S1–S4 module [19, 20]. A coiled-coil motif comprising residues of E684–R721 and overlapping with the TRP domain in the C-terminus of TRPV1 has been identified as an association domain and appears to be the molecular determinant of tetramerization [21]. In TRPV3, the C-terminal domain additionally forms a loop of 19 residues from V737 to V756, which has not been observed in other TRPV channels. This unique C-terminal loop domain extends along the TRPV3 intracellular skirt and forms an extensive network of interactions with ankyrin repeats 2–5 of the ARD [22]. Among all of these domains, several regions and specific residues have been mapped within TRPV1 and TRPV3 to regulate the channel gating. Indeed, heat, voltage, and ligand stimuli are sensed by TRPV channels by different structural domains.
Figure 2.
TRPV1 and TRPV3 structure. Left – Highlighting the fixation sites of TRPV1 activators (heat, capsaicin) and interacting protein (calmodulin). Right – Fixation sites of TRPV3 activators (2-APB, carvacrol, camphor, heat), interacting protein (calmodulin) and mutations involved in the establishment of the inflammatory response (G573A, G573C, G573S). Ankyrin repeat domain and TRP domain are conserved in TRPV1 and TRPV3 structures.
2.3 Pore module
Both pores of TRPV1 and TRPV3 are prone to dilatation during stimulation, rendering them permeable for large cations [19, 23]. Thus, TRPV1 and TRPV3 are cation-selective channels exhibiting a notable preference for divalent cations, with the following permeability sequence: Ca2+ > Mg2+ > Na + ≈K+. As for all TRPV channels, negatively charged amino acids in the pore play a central role in cation permeation, and furthermore, the opened pore is blocked by both extra- and intracellular cations. The S5-S6 segments are forming the central pore and the lower gate. This lower gate is formed by a hydrophobic seal, blocking permeation by hydrated ions when the channels are in their closed state. This hydrophobic seal is ensured by the critical residue I679 on S6 for TRPV1 and M677 on S6 for TRPV3 [20, 22]. An additional upper gate is formed by a short loop and helix between S5 and S6, called the pore helix (PH), and acts as a selectivity filter. TRPV1 displays a prolonged loop of 23 residues between S5 and the PH, named the pore turret. This pore turret is a mandatory structural domain for conformational rearrangements during heat activation of the TRPV1 channel, but is not part of the capsaicin agonist activation pathway [24, 25]. In TRPV3, the three key amino acids I644, N647, and Y661 located in the S6 are responsible for heat activation of the channel, since single-point mutants of these generate total loss of temperature activation, without affecting the overall TRPV3 structure [26]. Interestingly, the temperature sensitivity of the TRPV1 channel also implies the C-terminal domain [27].
2.4 Ligands
TRPV1 can be activated by numerous exogenous agonists including capsaicin, plant toxin resiniferatoxin (RTX), natural substances such as capsaicin-related compounds from peppers, aromatic components, and animal vanillotoxins from the venom of the tarantula [28, 29]. For TRPV1, the three amino acids R491, Y511, and S512 in the S3 transmembrane segment are responsible for capsaicin sensitivity, while the region between S481 and T550 is responsible for binding of the antagonist capsazepine, without affecting the temperature activation [30, 31]. Natural substances also activate TRPV3, including camphor (C612 and C619), carvacrol, thymol, and eugenol [32]. Moreover, TRPV3 can be activated by synthetic molecules such as the well-documented 2-Aminoethoxydiphenyl Borate (2-APB).
2-APB is a common activator ligand of TRPV1 and TRPV3 channels [27]. In TRPV3, several transmembrane segments are implicated in the binding of the agonist 2-APB. In fact, there are three different sites of 2-APB fixation in TRPV3. A first site of fixation is involving S444 of S1, E501 and W493 of S2, and Y565, H523, and F526 of S3 that establish complementary interactions with different atoms of 2-APB [22]. A second site of 2-APB binding is mostly mediated by polar residues, such as H417 and T421 of the linker domain, H426 and H430 of the pre-S1 helix, and R693 and R696 of the TRP domain. Interestingly, the mutation H426A completely abolishes TRPV3 activation by 2-APB but not by camphor neither by carvacrol [22, 33, 34]. However, the residue R696 in the TRP domain appears critical in TRVP3 activation by external ligands since the mutation R696K abolishes 2-APB- and carvacrol-induced calcium influx [34]. The third site of 2-APB fixation is nested in a cavity formed by the extracellular portions of helices S1-S4 and is mediated through both hydrophobic and hydrophilic residues including V458, Y540, R487, and Q483 [22]. The binding of 2-APB on the first two sites described above does not induce gating-associated conformational changes. In opposite, dramatic structural rearrangements are observed when 2-APB binds the third site [22]. Thus, binding of 2-APB to the first two sites is likely a prerequisite for gating, by stabilizing the multiple domains during channel opening.
Endogenous ligands were also reported for TRPV1 and TRPV3: unsaturated N-acyldopamines, lipoxygenase products of arachidonic acid, linoleic acid, Phospholipase C metabolites, and the endocannabinoid anandamide [35].
2.5 Sensitization/desensitization
In both TRPV1 and TRPV3, the N-terminus module contains a domain able to bind calmodulin (CaM) in a Ca2+-dependent manner [36]. This domain is located between the ankyrin repeats 2 and 3, which comprise a conserved site (K155 and K160 for TRPV1; K169 and K174 for TRPV3) involved in both CaM and ATP binding [37, 38]. In a resting cell, ATP is bound, and the channel is sensitized. Indeed, it has been shown that ATP binding to the TRPV1-ARD generates larger currents in response to capsaicin application [39, 40]. Hence, after channel opening, Ca2+ flows inward and chelates the ATP, which is released from TRPV1-ARD, thus freeing the binding site. In parallel, the Ca2+ influx activates CaM, and Ca2+-CaM can replace the sensitizer and engages the ARD to close the channel [40]. Thus, CaM is involved in Ca2+-dependent desensitization of TRPV1 [41].
The binding of ATP and Ca2+-CaM to the N-terminal ARD observed in TRPV1 is conserved in TRPV3 [38], although differences exist. TRPV1 is desensitized after cumulative stimulations. In contrast, TRPV3 is the only member among the TRP channels that sensitizes upon repeated application of stimuli. In addition, the sensitization of TRPV3 is independent of the origin of the stimulus, it will sensitize regardless whether it is activated by heat or chemical ligands. TRPV3 also displays cross-sensitization to stimuli of a different nature, as camphor stimulation causes a sensitization to heat [42]. It is known that sensitization is due to the decrease of the inhibition by calcium from both sides of cells [43]. In the intracellular side, Ca2+-CaM binds ARD and inhibits TRPV3, as described above for TRPV1. The TRPV3-ARD structure is very close to ARD from other members of TRPV channel family, except it exhibits a unique particular conformation of finger 3 loop. This linker region in between the ankyrin repeats 3 and 4 is greatly stabilized by a network of hydrogen bonds and an hydrophobic environment, instead of being flexible as seen in the other TRPV-ARD arrangements [44]. This stabilized finger 3 of TRPV3-ARD may cause steric hindrance, which impedes the binding of CaM. Therefore, CaM binding to ARD probably forces a conformational change of finger 3, thus resulting in an inhibition of TRPV3 function. Upon successive simulations, the finger 3 of TRPV3-ARD undergoes conformational change that decreases the binding of CaM, causing the channel to open more easily. Thus, the finger 3 of TRPV3-ARD functions as a switch in regulation of TRPV3 upon stimulation. Moreover, this distinctive finger 3 segment precedes a conserved threonine 264, which has been identified as a putative site for the ERK1-dependent modulation of TRPV3 [45]. Phosphorylation events could, therefore, alter the conformation of this important loop and powerfully influence the binding of regulatory factors [46]. In others contexts, the influence of phosphorylation events has been demonstrated especially for TRPV1, where phosphorylation of the channel induces sensitization, whereas dephosphorylation is associated to desensitization [47]. The TRPV1 C-terminus also contains modulatory domains able to be phosphorylated and to bind CaM through the 35 amino acids segment E767–T801 [41, 48].
In contrast to TRPV1, the naive TRPV3 channel does not show any intrinsic voltage-dependent activation. The voltage dependence only appears when the TRPV3 channel is primo-stimulated by chemicals or heat stimulus [43, 49]. This voltage dependence of TRPV3 is established by Ca2+ binding on N641 at the pore loop after opening. In addition, the voltage dependence is strongly influenced by Ca2+-CaM binding at the cytoplasmic N terminus. Sensitization is accompanied by a decrease in the voltage dependence. Finally, the sensitized TRPV3 channels are less inhibited than the naive ones, showing faster activation at positive potentials and less deactivation at negative potentials. This gradual shift in Ca2+-dependent regulation or TRPV3 activity is likely related to conformational changes after successive stimulations [43, 44, 46]. Considering the huge complexity in the structural arrangement and interactions of the multiple domains of the TRPV channels, it has been difficult to fully decipher the mechanisms of gating, and many questions remain open.
3. TRPV1 and TRPV3 channels in skin function
3.1 Epidermal barrier function
Ca2+ is well known to contribute to epidermal homeostasis and thus to the formation of an effective skin barrier [50, 51]. In order to maintain its barrier function, the epidermis needs to be renewed every 28 days depending on a calcium gradient. The increase in calcium concentration in the outer layer is essential for the terminal differentiation of keratinocytes, which will lead to the formation of the stratum corneum and ensure the skin’s physical barrier role [51]. This supports the role of calcium-permeable channels in epidermal barrier function.
The role of TRPV3 in the epidermal differentiation process was highlighted after aberrant expression of early differentiation markers (i.e., KRT1/KRT10) in keratinocytes from Trpv3-KO mice [52]. In addition, the decrease in transglutaminase activity contributed to an alteration in the stratum corneum formation. This regulation of keratinocyte differentiation process appears to be dependent on the TRPV3/TGFα/EGFR signaling axis [52, 53]. These data support the importance of TRPV3 channels as actors in the balance between proliferation and differentiation, thus giving them a crucial role in skin barrier formation. In contrast, the contribution of TRPV1 channels in the skin barrier remains unknown.
3.2 Sensory modalities in the healthy skin
TRPV1 is a major nonselective cation channel with polymodal mechanisms of activation [54]. Functional TRPV1 serves as a thermal sensor since it is gated by noxious heat greater than 42°C and also chili pepper [9, 55]. The heat nociception was almost abolished following ablation of TRPV1-expressing neurons in mice [56], but Trpv1-knockout mice display only a partial defect in the ability to sense and respond to acute noxious heat [57]. Partial explanation could be that three channels, including TRPV1, TRPM3, and TRAP1, act in concert to mediate behavioral responses to noxious heat [58]. Besides heat, TRPV1 channels can be directly activated by proton, such as extracellular acidification (pH less than ~6.0) [9, 59]. Consistently, an integrative study performed in healthy rats has shown that cutaneous vasodilation in response to cathodal stimulation was induced by TRPV1 channels, likely through local acidification and the PGIS/PGI2/IP pathway [60].
In contrast to TRPV1, TRPV3 was reported as a warm sensor for innocuous temperatures (approximately 33°C) in different in vitro studies [13, 14, 16] . Not surprisingly, a profound deficit in sensing warm external temperatures was described in mice lacking Trpv3 [15]. Later it has been shown that Trpv3-KO mice displayed a preference toward cooler temperatures [61], showing that TRPV3 influences thermal information that is used to modulate thermal comfort or preference. TRPV3 on keratinocytes has been shown to play a role in thermosensation involving ATP signaling, but other molecules have also been reported [62] . The overexpression of TRPV3 in keratinocyte induces the release of PGE2, an algogenic substance. Interestingly, in mice overexpressing Trpv3 channels selectively in keratinocytes, an hyperalgesia was observed [63]. These data support that TRPV3 channels participate to the thermal and pain transduction through these mediators. More recently, in vivo demonstration was provided for the role of cutaneous Trpv3 as a warm sensor of heating and a strong modulator of cutaneous vascular thermoregulatory mechanisms [64]. Since keratinocytes are representing the primary site of action of TRPV3 in mice (see the above section on TRPV3 expression), this study indicates that TRPV3 channels in the keratinocytes serve as heat detectors for warm temperatures to regulate cutaneous thermal homeostasis via initial changes in local blood flow. In contrast, TRPV1 channels are not involved in this process since Trpv1-KO mice displayed a normal heat-evoked vasodilation. It is interesting to note that Trpv3-KO mice showed a delay in behavioral response to noxious temperature over 50°C and 55°C, indicating that TRPV3 is also involved in response to acute painful heat stimuli [15]. This coincides with the ability to sensitize TRPV3 upon noxious heat stimuli [13]. Since Trpv3-KO mice and Trpv1-KO mice have an identical thermal nociceptive phenotype, this suggests that these two channels have overlapping thermal detection and functions.
4. TRPV1 and TRPV3 channels in psoriasis
Psoriasis is a chronic multifactorial inflammatory disease, resulting from the interaction between genetic predisposing factors and environmental triggers, with a global incidence ranging between 0.09% and 5.1% [65]. This dermatosis results from altered signaling between epidermal keratinocytes and the immune system leading to an uncontrolled keratinocyte proliferation (hyperplasia), impaired keratinocyte differentiation (hyperkeratosis), and chronic inflammation. The immune cells (i.e., dendritic and T cells) infiltrating skin lesions produce a wide variety of cytokines (IL-23, IL-17, IFNγ), which activate keratinocytes [66, 67]. Once activated, keratinocytes produce pro-inflammatory cytokines (i.e., IL-6, TNFα), chemokines (i.e., CXCL1, CCL2, CCL13), and antimicrobial peptides (cathelicidin, β-defensine) that further stimulate immune cells and thus maintain the disease in a chronic state. Therefore, keratinocytes not only respond to inflammation but also contribute to the recruitment and the activation of immune cells. Moreover, TRPV1 and TRPV3 channels have a predominant role in inflammation, pain, and pruritus and could be involved in the vicious cycle of the inflammation process in psoriasis.
Indeed, TRPV1 overexpression has been found in the skin of psoriatic patients and in the mouse model of “imiquimod-induced psoriasis” [68, 69]. Imiquimod (IMQ) is a potent immune activator stimulating the IL-23/IL-17 axis and thus mimicking psoriasis inflammation [70]. In 2014, Riol-Blanco et al have shown that ablation by RTX of TRPV1+/NaV1.8+ nociceptors reduces immune cells infiltration and psoriasis skin inflammation, by acting on IL-23 and IL17 release (Figure 3) [71]. Furthermore, this study revealed that TRPV1+/NaV1.8+ nociceptors can interact with dermal dendritic cells to regulate the IL-23/IL-17 axis during the initiation phase of psoriasis. Further data support a role for TRPV1 in this skin disease. In 2018, Zhou et al. also highlighted a significant decrease in epidermal hyperplasia, inflammatory cell infiltration, and cytokine production (IL-1, IL-6, IL-23) in IMQ-treated Trpv1-KO mice [69]. The NGF-TrkA-TRPV1 signaling pathway in nerve fibers has also been shown to play a role in psoriasis lesion formation [72]. Indeed, both nerve growth factor (NGF) and Tropomyosin receptor kinase A (TrkA) are highly expressed in psoriasis, and their interaction induces activation of TRPV1-mediated pain and pruritus [72, 73, 74]. Consistently, a TrkA kinase inhibitor (CT327) reduced pruritus of psoriatic patients (15). It is possible that NGF could sensitize TRPV1 channels on nerve fibers (NaV1.8+) during the initiation phase and then stimulate innate immune dermal dendric cells for the induction of IL-23/IL-17 signaling, leading to the development of psoriasis. Together, these data confirm the involvement of TRPV1 in psoriasis, with a major role of sensory nerve fibers.
Figure 3.
TRPV1 and TRPV3 in the physiopathology of psoriasis. Left – Inflammatory environment in skin psoriasis stimulates PAR2 on keratinocytes. Activated PAR2 stimulates TRPV3, which leads to the production of TSLP, an activator of the IL-23/IL-17 axis (red arrows). Inflammation also directly activates TRPV3, which leads to the production and the fixation of ATP and PGE2 on C-fibers, leading to pain and itch (blue arrows). Activated TRPV3 also stimulates and activates EGFR. In this context, the EGFR activation induces the transcription of NF-κB, allowing the production of inflammatory cytokines that sustain the inflammatory process in the skin. Right – In a psoriasis skin, keratinocytes release NGF in the extracellular environment. NGF can interact with TrkA present on the TRPV1+/Nav1.8 nerve endings. This interaction activates TRPV1 and leads to pain and pruritus. The interaction of dermal dendritic cells (DDC) with TRPV1+/Nav1.8 nerve endings potentiates the activation of the IL-23/IL-17 axis.
In contrast to TRPV1, TRPV3 channels seem to act on psoriasis from upper cell layers, such as keratinocytes. Indeed, TRPV3 channel expression is increased in psoriatic skin lesions, with significant labeling within the epidermis [68, 75]. Moreover, many studies have supported the role of TRPV3 on inflammation. Upon stimulation, TRPV3 can activate the EGFR/NFκB pathway and induce the release of mediators, such as IL-1α, IL-6, IL-8, TNFα, ATP, and PGE2 [53, 76], which will in turn act on sensory nerves and provoke pain and itching [62, 63]. In addition, Zhao et al. recently proposed that protease-activated receptor (PAR2) sensitizes TRPV3 channels on keratinocytes, resulting in secretion of thymic stromal lymphopoietin (TSLP), a potent pro-inflammatory cytokine. The latter then contributes to the production of IL-23 by dendritic cells and induces severe itching [77, 78]. Finally, the TRPV3 gain-of-function mutations G573S or G573C result in hyperkeratosis in mice, increased inflammatory cytokines in serum (IL-1α, Il-6, IL-17), and high levels of pruritogenic substances, such as NGF (Figure 3) [79, 80]. To further endorse the role of TRPV3 in inflammation, the 17(R)-resolvin D1, an anti-inflammatory lipid, is able to suppress TRPV3-induced hypersensitivity/pain during the inflammatory response in mice [81]. Moreover, injection of the TRPV3 antagonist 74a is able to attenuate pruritus and inflammatory response in mice with chronic inflammatory disease such as atopic dermatitis [77]. Thus, either through the activation of signaling pathways (EGFR/NFĸB; PAR2) or the release of algogenic and pruritogenic mediators, TRPV3 channels appear to play a role in the initiation of psoriasis.
Altogether, these data support that TRPV1 and TRPV3 are actors of inflammation, either from sensory nerve fibers or from keratinocytes. Both channels seem to have fundamental role in the pathogenesis of psoriasis due to their ability to activate immune cells or to induce cytokine production. It could also be hypothesized that these two channels cooperate during the initiation process of psoriasis.
5. TRPV1 and TRPV3 channels in therapeutic perspectives of psoriasis
The well-known biological strategies to treat an inflammatory disease such as psoriasis consist of using a specific blocking antibody to freeze the interaction of a cytokine with its receptor and then blocking the underlying cytokine-specific biological response. As mentioned earlier, both TRPV1 and TRPV3 are involved in the inflammatory process of psoriasis and could also be potential therapeutic targets in this disease. Indeed, TrkA appears to be a potential target because its inhibition with CT327 blocks the overactivation of TRPV1 on sensory neurons. The discovery of this new molecule is promising since the decrease in pain and pruritus has been observed in psoriatic patients [72]. Interestingly, another study also demonstrated a decrease in skin hyperplasia and erythema in psoriasis murine models treated with the TRPV1 antagonist SB366791 [82]. Research on the inhibition of TRPV1 in psoriasis disease has already emerged and needs to be further explored.
As the TRPV3/TGFα/EGFR signaling complex seems to play a role in psoriasis, EGFR also becomes a potential therapeutic target. A recent clinical study showed that erlotinib, an EGFR inhibitor, significantly decreases hyperkeratosis and pain in Olmsted syndrome patients displaying a TRPV3 overactivation mutation [83]. This highlights that inhibition of EGFR could decrease keratinocytes hyperproliferation/differentiation and might also act on inflammation and pain. Since TRPV3 acts at the first line, directly targeting this channel could also be very promising. Indeed, we reported above some anti-inflammatory molecules, such as 17(R)-resolvin D1, which suppresses TRPV3-induced pain and inflammation. Another potential promising molecule is the TRPV3 antagonist called 74a, which has already proved its efficacy on another inflammatory skin disease [77].
It could be suggested that inflammatory environment activates TRPV3 from keratinocytes and TRPV1+ nerves for the induction of pain, itching, and inflammation. The cooperation of these two channels, with the potential activation of TRPV1 induced by downstream mediators of TRPV3, cannot be excluded. To increase further the complexity of the TRPV1 and TRPV3 relationship, it has been demonstrated that TRPV1 and TRPV3 could form interacting partners, therefore assembling heterochannels [84, 85]. The biological significance of these heterochannels is still not known, but this could be involved in a very fine-tuning of sensitivity. In addtion, a recent study showed that the intergenic region between TRPV1 and TRPV3 coding sequences contained a human specific transposable element (SVA: SINE-VNTR-Alu retrotransposon) insertion, located upstream of the TRPV3 promoter and downstream of the 3′ end of TRPV1 [86]. This SVA insertion acts as a cis-regulatory element allowing coexpression of TRPV1 and TRPV3 in multiple human tissues, which is not observed in mice. Thus, targeting these two channels simultaneously could be a very promising approach for the treatment of psoriasis in human.
6. Conclusion
TRPV1 and TRPV3 are important channels for maintaining the skin homeostasis and its function. A deregulation of their expression and/or activity is associated to the establishment of an inflammatory response. Several studies already demonstrated their contribution in psoriasis by highlighting their capacities to activate typical inflammatory pathways (IL-23/IL-17 axis, NF-κB pathway) and/or to provoke the release of inflammatory mediators. It would therefore be interesting to explore the exact contribution of TRPV1 and TRPV3 in the psoriasis typical chronic skin inflammation: are they the trigger or are they one of the multiple factors involved in maintaining inflammation?
It would be interesting to explore the presence of TRPV1 and TRPV3 in other tissues of the body subjected to chronic inflammation, such as the intestinal epithelium. The future challenge will be to develop specific compounds that target the TRPV1/TRPV3 to limit chronic inflammation without affecting their physiological functions.
Conflict of interest
The authors declare no conflict of interest.
Notes
All of the artworks used were adapted from the illustration bank of Biorender (https://biorender.com).
\n',keywords:"skin, epidermis, TRPV1, TRPV3, calcium channel, inflammation, psoriasis",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80967.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80967.xml",downloadPdfUrl:"/chapter/pdf-download/80967",previewPdfUrl:"/chapter/pdf-preview/80967",totalDownloads:36,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 11th 2022",dateReviewed:"February 18th 2022",datePrePublished:"March 25th 2022",datePublished:null,dateFinished:"March 25th 2022",readingETA:"0",abstract:"Transient Receptor Potential Vanilloid (TRPV) channels are expressed in various skin cells, including non-neuronal cell types such as epidermal keratinocytes. They are polymodal sensors of the environment, regulating physiological function in response to a wide variety of stimuli. Indeed, in addition to their significant role in thermal responses and thermoregulation, TRPV channels are also implicated in local skin inflammation processes. Thus, these calcium permeable channels are associated to multiples skin diseases with inflammation, such as atopic dermatitis or psoriasis. In this chapter, we will mainly focus on TRPV1 and TRPV3 channels, as emerging pivotal targets for maintaining skin homeostasis in psoriasis-related inflammation.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80967",risUrl:"/chapter/ris/80967",signatures:"Lisa S. Martin, Emma Fraillon, Fabien P. Chevalier and Bérengère Fromy",book:{id:"10838",type:"book",title:"Ion Channels - From Basic Properties to Medical Treatment",subtitle:null,fullTitle:"Ion Channels - From Basic Properties to Medical Treatment",slug:null,publishedDate:null,bookSignature:"Ph.D. Zuzana Sevcikova Tomaskova",coverURL:"https://cdn.intechopen.com/books/images_new/10838.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-550-8",printIsbn:"978-1-80355-549-2",pdfIsbn:"978-1-80355-551-5",isAvailableForWebshopOrdering:!0,editors:[{id:"232970",title:"Ph.D.",name:"Zuzana",middleName:null,surname:"Sevcikova Tomaskova",slug:"zuzana-sevcikova-tomaskova",fullName:"Zuzana Sevcikova Tomaskova"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. TRPV1 and TRPV3 structure and gating",level:"1"},{id:"sec_2_2",title:"2.1 Expression and genetics",level:"2"},{id:"sec_3_2",title:"2.2 Common features",level:"2"},{id:"sec_4_2",title:"2.3 Pore module",level:"2"},{id:"sec_5_2",title:"2.4 Ligands",level:"2"},{id:"sec_6_2",title:"2.5 Sensitization/desensitization",level:"2"},{id:"sec_8",title:"3. TRPV1 and TRPV3 channels in skin function",level:"1"},{id:"sec_8_2",title:"3.1 Epidermal barrier function",level:"2"},{id:"sec_9_2",title:"3.2 Sensory modalities in the healthy skin",level:"2"},{id:"sec_11",title:"4. TRPV1 and TRPV3 channels in psoriasis",level:"1"},{id:"sec_12",title:"5. TRPV1 and TRPV3 channels in therapeutic perspectives of psoriasis",level:"1"},{id:"sec_13",title:"6. Conclusion",level:"1"},{id:"sec_17",title:"Conflict of interest",level:"1"},{id:"sec_14",title:"Notes",level:"1"}],chapterReferences:[{id:"B1",body:'Wong R, Geyer S, Weninger W, Guimberteau J-C, Wong JK. The dynamic anatomy and patterning of skin. 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NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. The EMBO Journal. 2005;24(24):4211-4223'},{id:"B74",body:'Raychaudhuri SP, Raychaudhuri SK. Role of NGF and neurogenic inflammation in the pathogenesis of psoriasis. Progress in Brain Research. 2004;146:433-437'},{id:"B75",body:'Seo S, Kim S, Kim S-E, Chung S, Lee S. Enhanced Thermal Sensitivity of TRPV3 in Keratinocytes Underlies Heat-Induced Pruritogen Release and Pruritus in Atopic Dermatitis. Journal of Investigative Dermatology. 2020;140(11):2199-2209.e6'},{id:"B76",body:'Szöllősi AG, Vasas N, Angyal Á, Kistamás K, Nánási PP, Mihály J, et al. Activation of TRPV3 Regulates Inflammatory Actions of Human Epidermal Keratinocytes. Journal of Investigative Dermatology. 2018;138(2):365-374'},{id:"B77",body:'Zhao J, Munanairi A, Liu X-Y, Zhang J, Hu L, Hu M, et al. PAR2 Mediates Itch via TRPV3 Signaling in Keratinocytes. The Journal of Investigative Dermatology. 2020;140(8):1524-1532'},{id:"B78",body:'El-Ghareeb MI, Helmy A, Al Kazzaz S, Samir H. Serum TSLP is a potential biomarker of psoriasis vulgaris activity. Psoriasis (Auckl). 2019;9:59-63'},{id:"B79",body:'Yoshioka T, Imura K, Asakawa M, Suzuki M, Oshima I, Hirasawa T, et al. Impact of the Gly573Ser Substitution in TRPV3 on the Development of Allergic and Pruritic Dermatitis in Mice. Journal of Investigative Dermatology. 2009;129(3):714-722'},{id:"B80",body:'Imura K, Yoshioka T, Hirasawa T, Sakata T. Role of TRPV3 in immune response to development of dermatitis. Journal of Inflammation (Lond). 2009;6:17'},{id:"B81",body:'Bang S, Yoo S, Yang T, Cho H, Hwang S. 17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel vanilloid 3 leading to peripheral antinociception. British Journal of Pharmacology. 2012;165(3):683-692'},{id:"B82",body:'Kemény Á, Kodji X, Horváth S, Komlódi R, Szőke É, Sándor Z, et al. TRPA1 Acts in a Protective Manner in Imiquimod-Induced Psoriasiform Dermatitis in Mice. The Journal of Investigative Dermatology. 2018;138(8):1774-1784'},{id:"B83",body:'Greco C, Leclerc-Mercier S, Chaumon S, Doz F, Hadj-Rabia S, Molina T, et al. Use of Epidermal Growth Factor Receptor Inhibitor Erlotinib to Treat Palmoplantar Keratoderma in Patients With Olmsted Syndrome Caused by TRPV3 Mutations. JAMA Dermatology. 2020;156(2):191-195'},{id:"B84",body:'Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, Facer P, et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature. 2002;418(6894):186-190'},{id:"B85",body:'Cheng W, Yang F, Liu S, Colton CK, Wang C, Cui Y, et al. Heteromeric heat-sensitive transient receptor potential channels exhibit distinct temperature and chemical response. The Journal of Biological Chemistry. 2012;287(10):7279-7288'},{id:"B86",body:'Price E, Gianfrancesco O, Harrison PT, Frank B, Bubb VJ, Quinn JP. CRISPR Deletion of a SVA Retrotransposon Demonstrates Function as a cis-Regulatory Element at the TRPV1/TRPV3 Intergenic Region. IJMS. 2021;22(4):1911.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Lisa S. Martin",address:null,affiliation:'
CNRS UMR 5305, Tissue Biology and Therapeutic Engineering Laboratory, France
CNRS UMR 5305, Tissue Biology and Therapeutic Engineering Laboratory, France
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The aim of this chapter is to provide an updated view of research issues in library and information science. A stratified random sample of 440 articles published in five prominent journals was analyzed and classified to identify (i) research approach, (ii) research methodology, and (iii) method of data analysis. For each variable, a coding scheme was developed, and the articles were coded accordingly. A total of 78% of the articles reported empirical research. The rest 22% were classified as non‐empirical research papers. The five most popular topics were “information retrieval,” “information behaviour,” “information literacy,” “library services,” and “organization and management.” An overwhelming majority of the empirical research articles employed a quantitative approach. Although the survey emerged as the most frequently used research strategy, there is evidence that the number and variety of research methodologies have been increased. 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Evidence-based maintenance consists of continuous monitoring of equipment performance, starting from evidence—the current state from the point of view of fault history—and improving its efficiency through the necessary modifications. This process is very important for optimizing the use and allocation of the resources available by the clinical engineering departments. Maintenance of medical equipment consists of two basic activities: scheduled maintenance and corrective maintenance. The purpose of this chapter is to present document-based methods to evaluate every aspect of the medical equipment maintenance process and to provide a correct, objective and standardized approach that supports clinical engineering activities. Following the analysis, the results show that the combination of the use of the two methods provides an overview, in a periodic manner, of maintenance performance that indicates the use of the most appropriate procedures.",book:{id:"10020",slug:"operations-management-emerging-trend-in-the-digital-era",title:"Operations Management",fullTitle:"Operations Management - Emerging Trend in the Digital Era"},signatures:"Călin Corciovă, Doru Andriţoi and Cătălina Luca",authors:[{id:"208834",title:"Associate Prof.",name:"Călin",middleName:null,surname:"Corciovă",slug:"calin-corciova",fullName:"Călin Corciovă"},{id:"319036",title:"Mr.",name:"Doru",middleName:null,surname:"Andriţoi",slug:"doru-andritoi",fullName:"Doru Andriţoi"},{id:"319037",title:"Ms.",name:"Cătălina",middleName:null,surname:"Luca",slug:"catalina-luca",fullName:"Cătălina Luca"}]},{id:"73966",title:"Project Management Concepts",slug:"project-management-concepts",totalDownloads:510,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter covers fundamentals of project management. It introduces project management concepts and provides a system view of project management plan and processes with which they are implemented. The knowledge areas include scope, time, cost, quality, and risk. The chapter will also emphasize on the interrelated nature of these knowledge areas. In addition to introducing these knowledge areas, the chapter will attempt to develop an understanding of these concepts and the important role of project teams in managing projects successfully. This chapter will also discuss similarities and differences between the plan-driven and change-driven (Agile) project methods.",book:{id:"10020",slug:"operations-management-emerging-trend-in-the-digital-era",title:"Operations Management",fullTitle:"Operations Management - Emerging Trend in the Digital Era"},signatures:"Vittal S. Anantatmula",authors:[{id:"323614",title:"Prof.",name:"Vittal S",middleName:null,surname:"Anantatmula",slug:"vittal-s-anantatmula",fullName:"Vittal S Anantatmula"}]}],onlineFirstChaptersFilter:{topicId:"439",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:36,paginationItems:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}}]},overviewPagePublishedBooks:{paginationCount:32,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. 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In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}}]}},subseries:{item:{id:"10",type:"subseries",title:"Animal Physiology",keywords:"Physiology, Comparative, Evolution, Biomolecules, Organ, Homeostasis, Anatomy, Pathology, Medical, Cell Division, Cell Signaling, Cell Growth, Cell Metabolism, Endocrine, Neuroscience, Cardiovascular, Development, Aging, Development",scope:"Physiology, the scientific study of functions and mechanisms of living systems, is an essential area of research in its own right, but also in relation to medicine and health sciences. The scope of this topic will range from molecular, biochemical, cellular, and physiological processes in all animal species. Work pertaining to the whole organism, organ systems, individual organs and tissues, cells, and biomolecules will be included. Medical, animal, cell, and comparative physiology and allied fields such as anatomy, histology, and pathology with physiology links will be covered in this topic. Physiology research may be linked to development, aging, environment, regular and pathological processes, adaptation and evolution, exercise, or several other factors affecting, or involved with, animal physiology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. 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