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IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
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\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
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\\n\\nNote: Edited in October 2021
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\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
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This book is a part of a four volume collection (covering material aspects, physical effects, characterization and modeling, and applications) and focuses on ways to obtain high-quality materials exhibiting large ferroelectric activity. The book covers the aspect of material synthesis and growth, doping and composites, lead-free devices, and thin film synthesis. The aim of this book is to provide an up-to-date review of recent scientific findings and recent advances in the field of ferroelectric materials, allowing a deep understanding of the material aspects of ferroelectricity.",isbn:null,printIsbn:"978-953-307-332-3",pdfIsbn:"978-953-51-4451-9",doi:"10.5772/702",price:159,priceEur:175,priceUsd:205,slug:"ferroelectrics-material-aspects",numberOfPages:532,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"4489eb7544dc5c1014f4e1280e677371",bookSignature:"Mickaël Lallart",publishedDate:"August 24th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/174.jpg",numberOfDownloads:79017,numberOfWosCitations:140,numberOfCrossrefCitations:42,numberOfCrossrefCitationsByBook:8,numberOfDimensionsCitations:107,numberOfDimensionsCitationsByBook:9,hasAltmetrics:0,numberOfTotalCitations:289,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 11th 2010",dateEndSecondStepPublish:"November 8th 2010",dateEndThirdStepPublish:"March 15th 2011",dateEndFourthStepPublish:"April 14th 2011",dateEndFifthStepPublish:"June 13th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7,8",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"10041",title:"Dr.",name:"Mickaël",middleName:null,surname:"Lallart",slug:"mickael-lallart",fullName:"Mickaël Lallart",profilePictureURL:"https://mts.intechopen.com/storage/users/10041/images/1517_n.png",biography:"Mickaël Lallart graduated from Institut National des Sciences Appliquées de Lyon (INSA Lyon), Lyon, France, in electrical engineering in 2006, and received his Ph.D. in electronics, electrotechnics, and automatics from the same university in 2008, where he worked for the Laboratoire de Génie Electrique et Ferroélectricité (LGEF). After working as a post-doctoral fellow in the Center for Intelligent Material Systems and Structures (CIMSS) in Virginia Tech, Blacksburg, VA, USA in 2009, Dr. Lallart has been hired as an Associate Professor in the Laboratoire de Génie Electrique et Ferroélectricité. 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This determines 50% of the total product cost and that is why it is necessary to try and create products using cheaper materials, but that still possess the same physical, chemical and mechanical properties.
\nThis phenomenon took place in China when the country started to create very cheap products, made possible thanks to the development of new, cheaper materials with the same mechanical properties as older, more expensive materials.
\nEven if cheaper materials are available, it is still necessary to assess their mechanical properties in order to decide whether the resultant product will be suitable.
\nIn addition, in order to assess the mechanical properties of materials, it is necessary to know their phases, and this need is addressed by the phase diagram. The next section describes this in more detail.
\nPhase diagrams in metallic alloys are a development of the relationship between the Gibbs free energy of the different phases that exist in a metallic mix. A phase is defined as “a portion of the system whose properties and composition are homogeneous and which is physically distinct from other parts of the system” [1].
\nGibbs free energy measures the stability of a system according to certain temperatures and pressures. This energy generates a curve on the graphic representation of energy vs atomic percentage, and when the system in question has different phases, then each phase will generate a curve (Figure 1(a)-(e)).
\nThe Gibbs free energy is defined by the equation: \n
Where:
\nE = Internal energy of the system
P = Pressure
V = Volume
T = Temperature
S = Entropy
In the case of binary alloys, the equation of Gibbs free energy is:
Where:
\nNa is Avogadro’s number
Z is the number of bonds per atom
ε is the difference between the A-B bond energy and the average of the A-A and B-B bond energies.
\nEquation (3) explain this further:
This can be simplified a little if Nazε = Ω
\nThe graphic of the binary alloy with respect to the Gibbs free energy at a constant pressure and temperature, is used to create the phase diagram. Figure 1 represents the formation of a phase diagram by the Gibbs free energy.
\nPhase diagram based on the Gibbs free energy in the liquid and solid phase.
Figure 1(a) shows both L and S phases, but in this case the L phase shows a lower energy in whole the combination percentage of the elements A and B. This indicates that the L phase is present in whole the combination of two elements at temperature T1, and this is shown in the phase diagram Figure 1(f), where it can be observed that the temperature T1 is only observed the L phase in whole combination of elements A and B. If the curves generated is intercepted at a point in the temperature Tm, as is the case of Figure 1(b), where an interception of the L and S phases can be observed. After this point, the L phase possesses less energy.
\nThis is reflected in the phase diagram, where the temperature Tm (A) is observed in both phases at the initiation of the combination of A and B, and is later seen in the L phase only [2].
\nWhen the curves of Gibbs free energy intersect at certain temperatures, e.g. temperature T2, then the phases are mixed. This mixing occurs in the tangent line between the curves of the L and S phases (Figure 1(c)). At the point where element A begins, to the point of interception with the tangent line, only the S phase is present. In the points where the curves are intercepted by the tangent line, a mix of L and S phases is obtained. Finally, from point c to the start of element B, only the L phase is present.
\nAs Figure 1 shows, at a certain temperature it is possible to have a mix of phases. This is important because the proportion of the phases determines the mechanical, physical and chemical properties of the metallic alloys.
\nIn the previous investigations, equations were obtained that link hardness with chemical percentage — that is to say with the tangent line of the curves of Gibbs free energy. It is therefore necessary to understand the mathematical form in which the tangent line is obtained.
\nIn order to better understand this, the example below shows the creation of a tangent line to two parabolas represented by the equations:
The curves generated by equations (4) and (5), and the tangent line are shown below in Figure 2:
\nGraphic of equations (
The tangent line shown in Figure 2 is represented by equation (6):
However, at some points equation (6) is intercepted by equations (4) and (5) and then:
If we pass all of the left side of the equations, then:
The equation is solved using the quadratic equation:
However, equation (6) touch in only point to the equations (4) and (6), therefore when is applicate the quadratic equation the result into of square root.
By developing:
Then the quadratic equation is used:
As the slope is the same, it is possible to match equations (15) and (16).
Therefore, b is:
With this value, using equation (15) or (16) it is possible to obtain m:
The equations are equal when m = −3.4495
\nThe linear equation representing the tangent to each curve is:
Using this method we can obtain the linear equation generated by the curves of Gibbs free energy in a regular solution. For example:
For phase 1.
For phase 2.
\nSo:
And m is:
In equations (20) and (21), it is possible to appreciate that the change in the phases depends principally on Ω, and this is also Nazε. Therefore, the mechanical properties of any material are easily transposable directly by the bond energy that exists between atoms.
\n\nWhen applying this method to a ternary alloy, the procedure is essentially the same, with the difference being that instead of having a tangent line, we have a tangent plane to the parabolas composed of each of the phases. Figure 3 shows the formation of a ternary diagram from the curves of Gibbs free energy.
\nIn the same fashion as the binary phase diagram, from the ternary diagram the percentage of each phase that exists for each composition can be obtained in such a way that it is possible to determine the mechanical, physical and chemical properties of each alloy. Therefore, it is possible —based on the composition and accordance with the phase diagram — to obtain the relationship with hardness. This is explained further in the next chapter.
\nRepresentation of the ternary system curve developed with the Gibbs free energy [
Hardness is defined as the capacity with which a body can contain the penetration of another body with a certain resistance. The deformation resistance is:
Where F is the force and A is the surface area.
\nThe deformation of a sample during the indentation consist of two parts; the first part is elastic and the second is plastic.
\nTabor’s experimental studies suggest that hardness (H) is proportional to a representative tensile of contact σr;
The answer of contact for materials of high hardness is often to the deformation elastic-plastic. These materials are governed by the equation:
where E is Young’s modulus and equations (23) and (24) describe its relationship to the hardness. This is important because it is possible to obtain other mechanical properties only through the hardness.
\nIn the last 10 years, new techniques have been developed in the measurement of hardness, such as micro and nanoindentation, in order to enable the complete characterization of mechanical properties in small areas the size of micrometers.
\nThese techniques allow measurements of the curve force (P) and penetration (h). This curve describes the fundamental mechanical properties like Young’s modulus and the stress-strain curve [3–7]. The micro and nanohardness allow for an assessment of the mechanical conduits to different levels microestructurales. The difference between macro, micro and nanoindentation is the load force. For example, in microhardness, the minimum load is 200 mN while in nanohardness it is 0.01 mN. The problem with micro and nanoindentation, is that they only can characterize an extremely small region of the sample, speak in clear of metallic materials.
\nAlloy composed of L and S phases.
As previously mentioned, the points where a tangent line touches the two curves of the Gibbs free energy of each phase. Figure 4 shows this:
\n\nNanoindentation seen by electronic microscopy.
The mechanical properties of any alloy are between point b and point c of Figure 4, and depend on the percentage of each phase present. For example, the alloy (a-B), consists of L and S phases, and to determine the percentage of each phase according to the chemical composition, it is necessary to use the lever rule. The alloy (A-B) can be measured with normal hardness and by the size of the track it generates, covering the two phases. As a result, the hardness is the average of the phases. However, when the hardness was measured with a nanohardness, only one phase was measured. For example, in Figure 5 it is possible to appreciate the different phases present in the Al-Cu-Zn alloy. If we use conventional hardness, then the track is so big that it covers all the phases present, and nothing could observe the track to 4000 enhance.
\n\nThe phase present in alloys, depends on temperature and pressure, and hence distinct phase diagrams can be seen according to these two variables.
\nTernary phase diagram of Al-Cu-Zn alloy. The line crosses the zone composed by the α, η and τ phases [
Figure 6 shows a ternary phase diagram of Al-Cu-Zn alloy to 200°C, at atmospheric pressure. A diagram of this kind does not exist in the literature at room temperature and all that’s left is to think that keep the phases present of 200°C at room temperature. Figure 6 shows a line that crosses the zone composed of the α, η y and τ phases. Each point on this line is one alloy, with a different percentage chemical composition, and of phases, each of these alloys will have certain mechanical properties.
\n\nThe line that crosses the diagram can be modelled by a linear equation in such a way that this equation will have a relationship with the mechanical properties of the alloy. It is possible to assess the mechanical properties of each of the alloys that are on the line. The next section describes the methodology of the assessment of hardness, and the analysis of phases.
\n“The Al-Zn-Cu ternary system is one of the most important alloy systems. It is important for the 7xxx series Al-based alloys and Zn-Al based alloys, ZAMAK. For instance, Zn-Al-Cu alloys have been used in different tribological applications as a substitute to conventional bearing bronzes and cast irons. Nevertheless, these alloys have some limitations such as dimensional stability because of the transformation of the metastable (CuZn4) with a hexagonal crystalline structure into the stable τ’ (Al4Cu3Zn) phase with an ordered rhombohedric structure. It is formed by the four phase reaction
Two lines of work were developed, composed of 8 samples of each line, as shown in Figure 7. For line 1, the samples M1 to M8 were developed and for line 2 the samples M9 to M16 were developed. Table 1 shows the chemical composition of each of the samples.
\nTernary phase diagram of Al-Cu-Zn alloy, showing the two lines used. The points represent the alloys that were used in this work [
Every line is represented by an equation, so line one is represented by equation (25) and line two by equation (26).
where XZn and XCu are the atomic fractions of Zn and Cu respectively. The rest is Al, completing the 100%.
\nSample | \nCu | \nZn | \nAl | \nSample | \nCu | \nZn | \nAl | \n||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
%p. | \n%at. | \n%p. | \n%at. | \n%p. | \n%at. | \n%p. | \n%at. | \n%p. | \n%at. | \n%p. | \n%at. | \n||
M1 | \n5.00 | \n3.54 | \n63.18 | \n43.44 | \n31.82 | \n53.02 | \nM9 | \n5.00 | \n4.77 | \n89.60 | \n83.10 | \n5.4 | \n12.13 | \n
M2 | \n10.00 | \n6.87 | \n55.31 | \n36.96 | \n34.70 | \n56.17 | \nM10 | \n10.00 | \n9.02 | \n80.32 | \n70.42 | \n9.68 | \n20.56 | \n
M3 | \n15.00 | \n10.03 | \n47.43 | \n30.82 | \n37.57 | \n59.15 | \nM11 | \n15.00 | \n12.83 | \n71.04 | \n59.05 | \n13.96 | \n28.12 | \n
M4 | \n20.00 | \n13.01 | \n39.56 | \n25.02 | \n40.44 | \n61.97 | \nM12 | \n20.00 | \n16.26 | \n61.76 | \n48.81 | \n18.24 | \n34.93 | \n
M5 | \n25.00 | \n15.84 | \n31.69 | \n19.52 | \n43.31 | \n64.64 | \nM13 | \n25.00 | \n19.37 | \n52.48 | \n39.52 | \n22.52 | \n41.01 | \n
M6 | \n30.00 | \n18.53 | \n23.82 | \n14.30 | \n46.19 | \n67.17 | \nM14 | \n30.00 | \n22.20 | \n43.19 | \n31.07 | \n26.81 | \n46.72 | \n
M7 | \n35.00 | \n21.08 | \n15.94 | \n9.33 | \n49.06 | \n69.59 | \nM15 | \n35.00 | \n24.79 | \n33.91 | \n23.35 | \n31.09 | \n51.86 | \n
M8 | \n40.00 | \n23.51 | \n8.07 | \n4.61 | \n51.93 | \n71.88 | \nM16 | \n40.00 | \n27.17 | \n24.63 | \n16.26 | \n35.37 | \n56.57 | \n
Chemical percentage of each sample.
Each sample was prepared by the melting of pure elements at 750 °C under an argon atmosphere and then slow cooling. Alloys were homogenized at 350 °C for 180 h in order to eliminate the dendritic structure. All alloys were subsequently heated to 350 °C for 24 h and quenched to 2 °C in ice water to retain the crystalline structure. Metallographic specimens were examined using optical and scanning electron microscopy (SEM). X-ray diffraction (XRD) analysis of samples was determined according to the standard procedure and hardness in Rockwell B.
\n\nFigure 8 shows the phase diagrams at different temperatures (20 °C to 400 °C) obtained using the Thermo-Calc program and shows each alloy. Table 2 shows the phases obtained by this program for each alloy according to the temperature. When the temperature is between 25 °C to 200 °C, the phases are the same. Sample M11 shows the same phases (α, η y τ) between 20 °C to 400 °C. This explains the poor increase in hardness between different heat treatments. The rest of the samples present phase changes continuous with each heat treatment.
\nThe results of simulations using Thermo-Calc [
Fases | \nTemperature (°C) | \nMuestra | \nFases | \nTemperature (°C) | \nMuestra | \n
---|---|---|---|---|---|
τ, α | \n400 | \nM1 − M6 | \nL, η | \n400 | \nM9 | \n
θ, α, τ | \n400 | \nM7 – M8 | \nL, α, η | \n400 | \nM10 | \n
\n | \n | \n | τ, α, η | \n400 | \nM11 − M12 | \n
\n | \n | \n | θ, α, τ | \n400 | \nM13 − M16 | \n
\n | \n | \n | \n | \n | \n |
τ, α, α’ | \n350 | \nM1 a M4 | \nα, η | \n350 | \nM9 | \n
τ, α | \n350 | \nM5- M7 | \nτ, α, η | \n350 | \nM10 – M11 | \n
τ, α, θ | \n350 | \nM8 | \nτ, α | \n350 | \nM12 − M14 | \n
\n | \n | \n | τ, α, α’ | \n350 | \nM15 | \n
\n | \n | \n | τ, α | \n350 | \nM16 | \n
\n | \n | \n | \n | \n | \n |
τ, α, α’ | \n300 | \nM1 − M5 | \nτ, α, η | \n300 | \nM9 − M12 | \n
τ, α | \n300 | \nM6 – M7 | \nτ, α | \n300 | \nM13 | \n
τ, α, θ | \n300 | \nM8 | \nτ, α, α’ | \n300 | \nM14 − M16 | \n
\n | \n | \n | \n | \n | \n |
τ, α, η | \n25 | \nM1 – M7 | \nτ, α, η | \n25 | \nM9 − M16 | \n
τ, α, θ | \n25 | \nM8 | \n\n | \n | \n |
Phases present in each sample at specific temperatures according to Thermo-Calc.
Samples M1 to M8 show many changes in phase between 20 °C to 300 °C, compared to samples M10 and M11. Therefore, and as can be seen in the hardness results, samples M1 to M8 have an increase in the hardness of heat treatment to other.
\nThe Thermo-Calc program also shows that the Börnstein’s diagram is perfectly in line with these observations.
\nThe diffraction patterns of samples M1 to M8, and M9 to M16 are presented in Figures 9 and 10 respectively.
\nFigure 10 shows that α, η, ε and τ phases are present in nearly all as-cast alloys. “The increase in Cu content was observed to be related to the increase in the intensity of X–ray diffraction peaks corresponding to the θ phase. This phase may be formed by the eutectic reaction L → α + θ located in the Al-Cu rich side. In contrast, the peak intensity of the Zn-rich η phase also increases with an increase in Zn content. This fact suggests the increase in the volume fraction of this phase. The amount of α and ε phases showed no clear tendency to increase or decrease the contents of either Al or Zn. A low volume fraction of the β phase is present in the as-cast M1 to M7, M9, and M14 to M16 alloys. This presence seems to indicate that the chemical compositions of alloys on line 1 are closer to the β phase field at high temperatures than the alloy compositions on line 2. Likewise, the τ´ phase is, in general, more stable as the Cu content increases. This suggests that the four-phase reaction,
Diffraction pattern in as-cast alloys of samples M1 to M8.
Diffraction pattern in as-cast alloys of samples M9 to M16.
Micrographs taken by SEM of samples M2, M7, M10 and M15 are shown in Figure 11.
\nThe micrographs show that there is an increases in the percentage by volume of the θ phase with respect to an increase in the quantity of Cu and Al. All samples with a low Cu and Al content show a very heterogeneous microstructure, while samples with a high content of these elements show a uniform appearance.
\nSEM Micrographs of different as-cast samples, (a) sample M2, (b) sample M7, (c) sample M10 and (d) sample M15.
Figures 12 and 13 show the diffraction patterns of the homogenized samples M1 to M16.
\nDiffraction pattern of the homogenized samples M1 to M8.
The ε phase appears in samples M1 to M3. This is important because the phase is present in the transformations of the four phases. Samples M4 to M8 do not have the ε phase, but they have the θ phase, which is more stable because it is not involved in the transformation of the four phases [12]. In the samples of series two, the ε phase is presented in samples M9 to M13, and the θ phase in samples M15 to M16 even though it should be emphasized that in these samples the β phase is present. It should be remembered that the β phase, in accordance with Aragon’s investigations [13] occurs after quenching and then disappears after this to room temperature when Cu is present in small proportions. However, when the content of Cu is enhanced, the β phase is retained and is harder to eliminate.
\nDiffraction pattern of the homogenized samples M9 to M16.
It can also be observed that an enhanced volumetric of the θ phase causes an increase in the hardness of the samples.
\nFigure 14 (a) and (b) show the diffraction patterns after quenching. Samples M1 to M4, and M9 to M11 show the same phases as follow the process of homogenization. However, when comparing the diffraction patterns of homogenized and quenching alloys of these samples, an increase in the intensity of both τ and α phases can be observed. It should be noted that the samples are solid and not in powder form, therefore there is texture, but even so it is possible to observe an increase in the phases.
\nFigure 15 shows micrographs of samples M2 (a–b) after homogenized, and sample M8 (c–d) after quenching. We can see that in sample M2 there is no dendritic structure. Moreover, when we compare samples M2 and M8, it can be seen that an increase in the quantity of Al and Cu enhances the percentage of the θ phase.
\nDiffraction patterns of samples M1 to M16 after quenching: (a) samples M1 to M8, (b) samples M9 to M16.
Micrographs of samples M2 and M8: (a) Sample M2 homogenized to 400X, (b) Sample M2 homogenized to 1000X, (c) Sample M8 quenching to 400X, (d) Sample M8 quenching to 1000X.
The hardness obtained from each of the samples, namely as-cast, homogenized and quenching, is shown in Figure 16. Each thermal process of the series 1 compound for samples M1 to M8, as well as the series 2 compound for samples M9 to M16, shows a linear trend.
\nGraphic of the hardness of samples M1 to M16 subjected to different heat treatments, (a) as-cast; (b) homogenized and (c) quenching [
Using a least squares regression produces a correlation coefficient of between 0.82 and 0.97, indicating a good fit. The table shows the equations that relate the hardness to the chemical composition of each of the samples.
\nThe equations in Table 3 are used in order to provide an assessment of hardness according to chemical composition. In these equations, the value of only one of the three elements used in the alloy is present. As a result, it is necessary to use equations 27 and 28. If a certain hardness is desired in accordance to a certain heat treatment, then we use the equation relating to that heat treatment. For example, if you want to have 65 RB after a homogenized heat treatment, then the homogenized equation of Table 3 should be used, but the series 1 and 2:
Treatment Thermic | \nEquation | \nR2 | \n
---|---|---|
Series 1 | \n||
As-Casting | \nHB = 10.12 lnXCu + 111.38 | \n0.8673 | \n
Homogenizad | \nHB = 18.617 lnXCu + 122.12 | \n0.9464 | \n
Quenching | \nHB = 8.1666 lnXCu + 113.81 | \n0.8197 | \n
Series 2 | \n||
As-Casting | \nHB = 23.334 lnXCu + 133.63 | \n0.9169 | \n
Homogenizad | \nHB = 33.326 lnXCu + 146.05 | \n0.9704 | \n
Quenching | \nHB = 25.211 lnXCu + 134.83 | \n0.9186 | \n
Equations generated from linearly regressing each heat treatment with respective values of R2.
To resolve XCu:
In order to know the atomic fractions of Zn and Al, equations (25) and (26) are used,
Therefore, in order to have an alloy with 63 RB, it is necessary to have 4.204 % at. Cu, 42.16% at. Zn and 56.63% of Al in the case of series 1.
\nHowever, it is also possible to obtain 63 RB by using 8.27% at. Cu, 72.66% at. Zn and 19.06% at. Al.
\nAs can be seen, it is possible to obtain the same hardness, but with a different chemical composition. If we want to use less of the more expensive Cu, then there is a need to use an increased amount of Al, whereby we can have a product with the same mechanical properties but at a cheaper cost. For example, the international standard cost of Aluminum is 1.55 dollars/kg, the cost of Cu is 8.2 dollar/kg and that of Zn 2.07 dollars/kg. If we require an amount of 100 kg of the product, then the cost will be of 247.86 dollars using a larger quantity of Cu. If the same product is made but a larger quantity of Al and Zn is used, then the cost is 204.82 dollars, making a saving of 17.36% —almost a fifth of the total product.
\n(a) Representation in cartesian coordinate of equations (
Using the equations it is possible to produce an assessment of the hardness of any alloy that is found in the line of either series 1 or 2. However, it is also possible to produce an assessment of the hardness of any alloy which is situated between the two series. It must be remembered that equations (25) and (26) provide the chemical composition of any alloys that are on either line. The difference between the lines of series 1 or 2 is the angle, and this is directly proportional to the slope of the hardness. For this reason, it is possible to relate the two. Figure 17 shows a cartesian coordinate where “x” is XCu (the atomic fraction of Cu) and “y” is XZn (the atomic fraction of Zn) and the angle is represented by Ω1 and Ω2.
\nIn order to determine the angle, it is necessary to use a virtual point that is the intersection of the two lines in Figure 7, or of equations (25) and (26). This point is virtual because the percentage of Zn is negative (-37.46 % at.), and for this reason it is impossible for this point to exist. However, the virtual point is useful in determining the angle of any alloy that exists between these two lines.
\nFor example, we can consider the alloy ZnAl27Cu3, which has 50.54% at. Zn; 2.23% at. Cu with the remaining percentage being Al [14]. The composition of ZnAl27Cu3 is only a point in the Cartesian coordinate and this point exists between line 1 and 2. When this point is joined with the virtual point, there is an angle of 63.99° as seen in Figure 17(b). As mentioned above, there is a direct relationship between the slopes, composition and hardness. This is because the percentage of each of the phases changes with the chemical composition. Therefore it is necessary to elucidate the relationship between the angle in the Cartesian coordinate in the chemical composition (Figure 17), and the angle in the graphic of the hardness vs lnXCu. For example, the angle of line 1 in the cartesian coordinate of the composition has a value of 62.78°, but the angle in the hardness in as-cast, is 84.74° and the same is occurs with line 2. In the case of the alloy ZnAl27Cu3, the angle of hardness is found by interpolation, as seen in \nTable 4.
\nSample | \nAngle (Percentage at. of each element) | \nAngle (Hardness in as-cast) | \n
---|---|---|
Line 1 | \n62.78° | \n84.74° | \n
ZnAl27Cu3 | \n63.99° | \n85.13° by interpolation | \n
Line 2 | \n71.47° | \n87.55° | \n
Results of the angles of each of the series according to its composition and hardness in as-cast.
Once the slope of hardness in the ZnAl27Cu3 alloy is present, the hardness intercept is then required. For this, is necessary to first obtain the hardness equation and then subsequently the hardness of the alloy according to the chemical composition. The intercept of the origin is obtained using the point of interception that exists between the equations of hardness. For example, the point of intersection in the equations in as-cast is 18.57% at. Cu and 94.34 RB. The point of intersection is shown in Figure 16(a).
\nAt this point, we have the slope, the hardness and the percentage Cu, therefore the equation is:
Solve for b
So the equations of the line that crosses for the ZnAl27Cu3 alloy is:
If the atomic percentage of ZnAl27Cu3 alloy is 50.54% at. Zn; 2.23 % at. Cu and the remaining percentage being Al then the hardness is:
The result obtained by Savaskan [14] was 67.15 RB with an error of only 5.43%. In this way, any alloy between the two lines can be assessed, as long as it has a heat treatment of as-cast, homogenized or quenching.
\nTables 5 and 6 show the assessment obtained by this method for certain alloys made by Savaskan and Ciach [14, 15].
\nSample | \nSavaskan et al. (2003) | \nAssessment | \nError (%) | \n
---|---|---|---|
ZnAl27Cu1 | \n64.74 | \n59.94 | \n7.41 | \n
ZnAl27Cu2 | \n66.21 | \n66.98 | \n1.15 | \n
ZnAl27Cu3 | \n67.15 | \n71.04 | \n5.48 | \n
ZnAl27Cu4 | \n68.5 | \n73.91 | \n7.32 | \n
ZnAl27Cu5 | \n70.75 | \n76.12 | \n7.05 | \n
\n | \n | Error average = | \n5.68 | \n
Comparative results of hardness as determined by Savaskan et al. (2003) and the assessment values.
Sample | \nSavaskan et al., (2003) | \nAssessment | \nError (%) | \n
---|---|---|---|
AlZn78Cu1 | \n73 | \n66.99 | \n7.41 | \n
AlZn78Cu2 | \n78 | \n73.12 | \n1.15 | \n
AlZn78Cu3 | \n81 | \n76.53 | \n5.48 | \n
\n | \n | Error average = | \n6.67 | \n
Comparative results of hardness as determined by Ciach et al. (1969) and the assessment values.
The same methodology can be used in any ternary alloy as long as there is a phase diagram, and this methodology can even be used with commercial alloys and the average error is only 5%. Therefore, it is possible to obtain alloys tailored to any ternary alloy, or to develop alloys cheaper or with better mechanical properties.
\nThe evidence from equations (20) and (21) shows a direct relationship between the bond energies of the atoms (Ω) and the mechanical properties in such a way that in future it will be possible to directly obtain the mechanical properties of bond energies.
The θ phase increases the hardness, and this phase intensifies along with an increase of Al and Cu.
The β phase along with ε phase causes a decrease in hardness.
The β phase remains to room temperature with an increase of Cu.
The simulation using Thermo-Calc enables a better understanding of the changes of phase shown in each of the samples.
The methodology presented here has been shown to be very effective, and it is possible use this methodology with other alloys.
It has also been shown that is possible to obtain alloys with similar mechanical properties, but at a cheaper cost.
Intercellular communication is essential to homeostasis and is largely dependent on the cellular secretome [1]. An emerging awareness of the role that the extracellular environment plays is evident in the field of secreted vesicles. The vesicular contribution to the tumor microenvironment (TME) has furthered our understanding of the communication between cells and the surrounding stroma [2]. This relationship has also elucidated many potential therapeutic targets and possible transporters of chemotherapeutics [3, 4]. There are multiple extracellular vesicle types, characterized by biogenesis, size, and common protein markers [5, 6]. Of these, exosomes are the smallest, with sizes ranging from 30 to 150 nm [6]. These vesicles have the most complex synthesis, emerging from the endocytic pathway. They arise from intraluminal invaginations into a multivesicular body (MVB) and are released from the cell when the MVB fuses with the plasma membrane. Exosomes consist of intracellular material surrounded by a lipid membrane that reflects the cellular membrane of the host cell [7]. These specific vesicles have demonstrated promise in several fields of research, including rheumatoid arthritis [8, 9] and neurodegenerative disease [10], but primarily in cancer [11, 12]. Tumor-derived exosomes (TEX) contain oncoproteins and oncogenes from the cell of origin and thus are very influential in intercellular communication. Numerous studies have used these luminal proteins and genes to better understand tumor growth and metastasis, as well as for improving diagnostic, prognostic, and therapeutic methods [13, 14].
\nWhile there has been an exponential growth in research focused on exosome biology, clarification on the mechanisms of transport between the cell of origin and the recipient cell is essential to maximizing on exosome potential in treating and diagnosing disease. The methods by which exosomes influence the cells with which they interact are still under review. Some exosomes have been shown to fuse to the recipient cell [15, 16], while others are internalized by specific receptor-ligand interactions [17, 18] or by stimulating an indirect uptake by macropinocytosis [19]. Exosome binding to cells has been seen both as a mechanism of transferring luminal contents [15, 16] and as an initial step in the endocytosis process [17, 20]. The significance of the effects of cell-exosome binding in comparison to internalization is still unknown. Most types of endocytosis have been described in the process of exosome uptake [21], but which factors determine the specific mechanism used, are still unclear. Previous reviews have clearly identified a number of ligands and receptors involved in exosome trafficking [21, 22, 23], but little is known about the dependence of uptake mechanism on cell-type. This review presents the current understanding of the endocytosis process utilized by specific cells involved in exosomal internalization.
\nEndocytosis is a basic cellular function that is performed by all cell types in the process of maintaining homeostasis. Many of the molecules essential for cellular function are small enough to cross the cell membrane either passively or actively, however, other structures, such as exosomes, are too large and require a more complicated process. This general process of internalization is called endocytosis and is separated into various types based on the shape [24] and the size of particles internalized [25]. There are many well-written reviews covering the specifics of the endocytic pathways [25, 26], but here we will address them only superficially. Classification under the umbrella of endocytosis varies, but the major methods include phagocytosis, macropinocytosis, clathrin-mediated endocytosis, caveolin-mediated endocytosis, and clathrin/caveolin-independent or lipid raft-mediated endocytosis [25, 26]. Receptor-mediated endocytosis (RME) is an additional type that is often considered to be a subcategory under several of those previously mentioned (Figure 1).
\nEndocytosis pathways involved in exosome uptake: (A) Phagocytosis, (B) Macropinocytosis, (C) Clathrin-mediated endocytosis, (D) Caveolin-mediated endocytosis, (E) Lipid Raft-dependent or clathrin−/caveolin-independent endocytosis, (F) Receptor-mediated endocytosis.
Phagocytosis is the mechanism by which specialized cells (such as macrophages and monocytes) engulf large particles (>0.5 μm) by way of receptor/ligand interactions [25, 27] (Figure 1A). Promiscuous receptors allow for a broad range of ligand recognition and binding, facilitating a key role phagocytes play in clearing apoptotic cells [27]. Exosomes, derived from a diverse population of cells, present a vast array of available ligands that make phagocytes ideal recipient cells. This process of phagocytosis is designed to not only internalize extracellular material by enveloping it, but also to regulate the immune response by presenting degraded proteins as antigens on the phagocyte surface [25]. Tumor-derived exosomes influence immune involvement in the tumor [28, 29] which may be facilitated by this mechanism of endocytosis. Other non-phagocytic cells, such as epithelial cells, Sertoli, liver endothelial, astrocytes, and cancer cells have also been shown to perform phagocytosis [27], potentially expanding the impact of exosomal communication. It is therefore important to define how the process of phagocytosis influences exosome function and if that influence is cell type dependent.
\nWhile phagocytosis or “cell eating” involves ingestion of large molecules, macropinocytosis (“cell drinking”) internalizes slightly smaller particles (>1 μm) [25] (Figure 1B). This method is a way for cells to sample the external environment without specific receptors or ligands. It is a constitutive process in specialized antigen presenting cells, but is stimulated by growth factors in most others [30]. Macropinocytosis has a unique membrane ruffling process caused by projections from the cell surface encircling extracellular fluid and fusing to the membrane [25], resulting in an increased membrane surface area and volume of engulfed material. Nakase et al., showed that stimulation of the epidermal growth factor (EGF) receptor, either by soluble EGF or exosome-bound, increased exosome internalization 27-fold through the activation of macropinocytosis [19].
\nThe next three mechanisms, clathrin-dependent, caveolae-dependent, and clathrin/caveolae-independent, are facilitated by specific membrane proteins/structures: clathrin, caveolae, and lipid rafts. Clathrin is an intracellular protein that forms a coat around an invaginating vesicle facilitating formation and internalization [31] (Figure 1C). These vesicles internalize material around 120 nm [25], which is within the exosome size range. Stimulation can occur through receptor/ligand mediation or can be constitutive, depending on cell-type and receptor presence, but clathrin-mediated endocytosis (CME) occurs in all cell types [31]. Data continues to show that the extracellular cargo of these clathrin-coated vesicles can drive the specific mechanisms and protein interactions of internalization [32], giving way for exosome surface proteins to influence uptake. Two proteins used extensively to describe the details of CME are transferrin (Tf) and low density lipoprotein (LDL) and their respective receptors [25], which are all (except LDL) found on the surface of exosomes [33, 34]. Overexpression of transferrin receptors on cancer cells [35] may also contribute to increased exosomal uptake and clathrin-mediated endocytosis in tumors, as there have been shown to be 50–80 percent more receptors on the cancer cell compared to the non-cancer cell [36].
\nCaveolin is similar to clathrin, as it forms a coat around membrane invaginations called caveolae and facilitates the entry of extracellular material (Figure 1D). These are particularly prevalent on endothelial cells but have been found on a wide distribution of cell types [25]. Caveolae are about half the size of clathrin-coated vesicles, limiting their cargo to smaller structures [25] but still covering some of the exosome size range. This type of endocytosis as well as lipid raft-dependent uptake, plays a key role in lipid transport and homeostasis [25]. One of the defining factors of the exosome membrane is its slightly altered lipid profile, which has been shown to influence internalization [37]. Two proteins commonly active in caveolae-dependent endocytosis, which have also been identified on the surface of exosomes, are the insulin receptor and albumin [34, 38, 39]. The cellular insulin receptor itself has also recently been found to influence exosome uptake [18].
\nLipid dependence is not only characteristic of caveolae-dependent endocytosis, but also clathrin/caveolae-independent processes. Lipid raft-dependent (or clathrin/caveolae-independent) endocytosis is similar to caveolae-dependent, except for the absence of the protein cav-1. Lipid rafts are 40-50 nm sections of the membrane with a high percentage of glycosphingolipids and cholesterol, and are anchoring points for many membrane proteins [40]. Lipid rafts are involved in exosome biogenesis and trafficking [41, 42, 43] and exosome uptake has been reduced by blocking lipid raft endocytosis [44] (Figure 1E).
\nAs mentioned previously, RME is an endocytosis pathway that can fit under several of the other categories (Figure 1F). The term and pathway were originally considered to be interchangeable with CME, but it is now understood that not all RME is dependent on clathrin [25]. Receptor-ligand interactions play a role in phagocytosis [25, 27], macropinocytosis [19], and lipid raft-dependent endocytosis [40]. Exosome internalization has been linked to multiple receptor-ligand interactions in each of these pathways [19, 20]. Each subtype of endocytosis has been identified in the exosome internalization process (Table 1) but additional research is needed to determine the driving factors behind the specific mechanisms. One hypothesized factor is that the recipient cell type may determine the specific type of internalization.
\nEndocytosis pathway | \nRecipient cell type | \nRecipient cell line | \nExosome cell of origin | \nReferences | \n
---|---|---|---|---|
Phagocytosis | \nMacrophage | \nRAW264.7 | \nLeukemia cell (K562 or MT4) | \n[20] | \n
\n | Macrophage | \nJ774 | \nRat reticulocyte | \n[52] | \n
\n | Macrophage | \nPrimary | \nTrophoblast (Sw71) | \n[58] | \n
\n | Monocytes | \nPrimary | \nActivated T cell | \n[50] | \n
\n | Macrophage | \nPeritoneal | \nMouse melanoma cell (B16BL6) | \n[51] | \n
\n | Macrophage | \nMouse bone marrow-derived | \nMouse CRC (CT-26) | \n[54] | \n
\n | Microglia | \nMG6 | \nPheochromocytoma (PC12) | \n[117] | \n
\n | Microglia | \nBV-2 | \nNeuron (N2a) | \n[49] | \n
\n | Dendritic cell | \nMouse primary | \nMouse dendritic cell | \n[15] | \n
\n | Epithelial | \nOvarian cancer (SKOV3) | \nOvarian cancer cell (SKOV3) | \n[97] | \n
\n | Epithelial | \nAlveolar cells (A549) | \nDendritic cell | \n[66] | \n
Macropinocytosis | \nEpithelial | \nCervical cancer (HeLa) | \nEpidermoid carcinoma (A431) | \n[90] | \n
\n | Epithelial | \nEpidermoid carcinoma (A431), Pancreatic carcinoma (MIA PaCa-2) | \nCervical cancer cell (HeLa) | \n[19] | \n
\n | Epithelial | \nOvarian cancer (SKOV3) | \nOvarian cancer cell (SKOV3) | \n[97] | \n
\n | Epithelial | \nBreast cancer (MCF7) | \nNormal breast epithelial cell (MCF-10A)—exosome mimetics | \n[96] | \n
\n | Endothelial | \nCerebral vascular (hCMEC D3) | \nMacrophage (RAW264.7) | \n[89] | \n
\n | Microglia | \nPrimary mouse | \nMouse oligodendrocyte (Oli-neu) | \n[56] | \n
\n | Neuron precursor cell | \nPheochromocytoma (PC12) | \nPheochromocytoma (PC12) | \n[114] | \n
Clathrin-mediated endocytosis | \nEpithelial | \nOvarian cancer (SKOV3) | \nOvarian cancer cell (SKOV3) | \n[97] | \n
\n | Epithelial | \nAlveolar cells (A549) | \nDendritic cell | \n[66] | \n
\n | Epithelial | \nGastric cancer (AGS, MKN1) | \nGastric cancer cell (AGS, MKN1) | \n[94] | \n
\n | Epithelial | \nBreast cancer (MCF7) | \nNormal breast epithelial cell (MCF-10A)—exosome mimetics | \n[96] | \n
\n | Endothelial | \nCerebral vascular endothelial (hCMEC D3) | \nMacrophage (RAW264.7) | \n[89] | \n
\n | Endothelial | \nBrain microvascular endothelial | \nEmbryonic kidney cell (Hek293T) | \n[87] | \n
\n | Neuron | \nCortical mouse neuron | \nOligodendrocyte (Oli-neu) | \n[115] | \n
\n | Neuron precursor cell | \nPheochromocytoma (PC12) | \nPheochromocytoma (PC12) | \n[114] | \n
Caveolin-dependent endocytosis | \nEpithelial | \nCervical cancer (HeLa) | \nEpidermoid carcinoma (A431) | \n[90] | \n
\n | Epithelial | \n(CNE1, HONE1, NU-GC-3, A549) | \nEBV-infected B cells | \n[95] | \n
\n | Epithelial | \nBreast cancer (MCF7) | \nNormal breast epithelial cell (MCF-10A)—exosome mimetics | \n[96] | \n
\n | Endothelial | \nCerebral vascular endothelial (hCMEC D3) | \nMacrophage (RAW264.7) | \n[89] | \n
\n | Endothelial | \nBrain microvascular endothelial | \nEmbryonic kidney cell (Hek293T) | \n[87] | \n
Lipid raft-dependent endocytosis | \nDendritic cell | \nMouse primary | \nMouse dendritic cell | \n[15] | \n
\n | Dendritic cell (DC), T cell | \nMonocyte derived primary DC, T cell (Jurkat) | \nT cell (Jurkat) | \n[75] | \n
\n | Epithelial, endothelial | \nGlioblastoma (U87), umbilical vein endothelial (HUVEC) | \nGlioblastoma (U87) | \n[43] | \n
\n | Epithelial | \nOvarian cancer (SKOV3) | \nOvarian cancer cell (SKOV3) | \n[97] | \n
\n | Epithelial | \nBreast carcinoma (BT549) | \nBreast carcinoma (BT549) | \n[44] | \n
\n | Epithelial, macrophage, endothelial | \nMelanoma (A375), (RAW264.7), dermal microvascular endothelial (HMVEC) | \nMelanoma (A375) | \n[46] | \n
\n | Endothelial | \nBrain microvascular endothelial | \nEmbryonic kidney cell (Hek293T) | \n[87] | \n
\n | B cell | \nMantle cell lymphoma (Jeko1) | \nMantle cell lymphoma (Jeko1) | \n[61] | \n
Endocytosis pathways involved in exosome internalization in various cell types.
As introduced previously, some cells are uniquely designed to internalize extracellular material through phagocytosis. Those cells generally considered “professional” phagocytes are monocytes, macrophages, and neutrophils [25] with dendritic cells, osteoclasts, and eosinophils occasionally included [27]. Phagocytosis is dependent on receptor/ligand interactions, relying on a vast array of different receptors and ligands. Some of the established receptors include Fc receptors, integrins, pattern-recognition receptors, phosphatidylserine (PS) receptors, and scavenger receptors [45]. Macrophage uptake of exosomes has been shown to involve many of these receptors including scavenger receptors [46, 47, 48], PS/PS receptors [20, 48, 49, 50, 51], lectins [17, 52, 53] and Fc receptors [54].
\nHowever, internalization of extracellular material by phagocytes does not always fit perfectly with the hallmarks of phagocytosis. Some phagocytic receptors, such as integrins (αvβ3), scavenger receptors (CD68 and CD36), and CD14, facilitate the tethering of apoptotic cells to the phagocyte surface, but then are unable to initiate internalization without other means, such as PS and PS receptor binding [55]. The PS/PS receptor interaction also stimulates membrane ruffling and vacuole appearance—classic hallmarks of macropinocytosis [55]. Phagocytes are primarily involved in phagocytosis, but this evidence supports the idea that multiple modes of endocytosis are operational in the same cell. This is not unique to apoptotic cell uptake, but has been seen with exosome internalization by microglia (phagocytic cells in the brain) exhibiting a dependence on PS in a macropinocytic manner [49, 56]. Cooperation between multiple receptors appears to be an important characteristic of endocytosis in phagocytic cells. Plebenak et al., showed that the scavenger receptor SR-B1 on macrophages, when blocked, reduces exosome uptake, but with further testing on melanoma cells this blocking was dependent both on the receptor as well as on cholesterol flux in the lipid rafts [46], broadening the endocytosis landscape of phagocytes to include lipid raft-dependent endocytosis.
\nThe dependence of phagocytosis on extracellular- facing PS, which on healthy cells is expressed only on the cytosolic side of the membrane, is evidence that the material to be ingested influences the endocytic pathway of phagocytes. Further support of this interaction is found in the hypothesis that exosomes “target” specific recipient cells [48, 57]. Macrophage uptake (Figure 2A) of TEX is dependent on the presence of cellular scavenger receptors or exosomal PS [20, 46, 48, 51, 56], while non-tumor cell-derived exosomes require the presence of a heterogeneity of receptors. When internalized by macrophages and monocytes, hepatic stellate cell-derived exosomes require Fc receptors [54]; B cell, dendritic cell and reticulocyte-derived exosomes use lectins [52, 53]; trophoblast-derived exosomes bind to integrins [58]; and T cell-derived exosomes need scavenger receptors [50] (Table 2). Costa-Silva et al., showed that when comparing TEX to normal cell-derived exosomes, Kupffer cells, liver-specific macrophages, preferentially internalized TEX [57]. The significance of the exosome surface topography is therefore influential in directing a specific endocytosis pathway. Phagocytes are responsible for internalization of extracellular material and are so named based on the primary use of phagocytosis, but as seen above, other endocytic pathways are utilized, especially in the context of exosomal internalization.
\nCell-specific internalization of exosomes by antigen presenting cells: (A) macrophage, (B) B cell and (C) Dendritic cells each employ multiple endocytic pathways in the uptake of exosomes. Macrophages utilize multiple endocytic pathways in the uptake of exosomes. B Cells and dendritic cells (DC) both employ multiple endocytic pathways in the uptake of exsomes. Lipid rafts, integrins and adhesion molecules are used by B cells while tetraspanins and adhesion molecules are the more common receptors found in DC-exosome interactions. Intercellular adhesion molecule 1 (ICAM-1), Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN).
Protein | \nCell type | \nExosome origin | \nReferences | \n
---|---|---|---|
Scavenger receptor | \nMacrophage | \nHek293 (embryonic kidney cells) | \n[47] | \n
Phosphatidylserine (PS) | \nMacrophage, microglia | \nNeuron, melanoma, oligodendrocytes | \n[49, 50, 51, 56] | \n
PS receptor | \nMacrophage | \nActivated T cells | \n[50] | \n
TIM4 | \nMacrophage | \nK562, MT4 (leukemia cell lines) | \n[20] | \n
Lectins | \nLymph node cells, splenic cells, pancreatic adenocarcinoma, lung fibroblast, macrophage, dendritic cell, hCMEC/D3(brain endothelial cells), platelet, HeLa | \nPancreatic adenocarcinoma, reticulocyte, B cell, macrophage, mesenchymal stem cell | \n[17, 48, 52, 53, 65, 89, 72, 103] | \n
Fc receptors | \nMacrophage | \nCT26 (colon carcinoma cells) | \n[54] | \n
Integrins | \nMacrophage, B cell | \nTrophoblast, pancreatic adenocarcinoma cells | \n[17, 58] | \n
Tetraspanins | \nB cell, pancreatic adenocarcinoma, endothelial cell | \nPancreatic adenocarcinoma cells | \n[17, 48, 106] | \n
EGFR | \nA431 (epidermoid carcinoma cells) | \nHeLa cells | \n[19] | \n
CD11c | \nLymph node cells/splenic cells | \nPancreatic adenocarcinoma cells | \n[17] | \n
CD11b | \nLymph node cells/splenic cells | \nPancreatic adenocarcinoma cells | \n[17] | \n
CD44 | \nLymph node cells/splenic cells | \nPancreatic adenocarcinoma cells | \n[17] | \n
CD49d/CD106 | \nLymph node cells/splenic cells | \nPancreatic adenocarcinoma cells | \n[17] | \n
Tspan8 | \nEndothelial cell | \nPancreatic adenocarcinoma cells | \n[48, 106] | \n
ICAM-1/LFA-1 | \nDendritic cell, hCMEC/D3 (brain endothelial cells), aortic endothelium, HUVEC | \nDendritic cells, pancreatic adenocarcinoma cells, T cells, macrophage | \n[16, 17, 37, 65, 69, 89] | \n
DC-SIGN | \nDendritic cell | \nBreast milk | \n[70] | \n
HSPG | \nU87 (glioblastoma cells), CAG (myeloma), HUVEC, SW780 (bladder cancer cells) | \nU-87 cells, myeloma cells, SW780 cells | \n[63, 99, 100, 101] | \n
Cad-11 | \nPC3-mm2 (prostate cancer cells) | \nOsteoblasts | \n[104] | \n
Syncytin | \nChoriocarcinoma cells | \nTrophoblasts | \n[105] | \n
SNAP 25 | \nNeuron | \nMesenchymal stromal cells | \n[116] | \n
CD62L | \nLymph node cells, splenic cells, pancreatic adenocarcinoma, lung fibroblasts | \nPancreatic adenocarcinoma | \n[17, 48] | \n
Galectin 5 | \nMacrophage | \nReticulocyte | \n[52] | \n
CD169/ α2,3-linked sialic acid | \nLymph node cells, splenic cells | \nB cell | \n[53] | \n
C-type lectin/C-type lectin receptor | \nDendritic cell, brain endothelial cell (hCMEC/D3) | \nMacrophage | \n[65, 89] | \n
P-selectin/PSGL-1 | \nPlatelet | \nMacrophage | \n[72] | \n
Proteins involved in exosomal uptake.
The antigen presenting cells (APCs) include primary phagocytes such as macrophages, but also B cells and dendritic cells [59]. The immune response is heavily dependent on the recognition of foreign structures, such as peptides, for activation. These APCs sample the extracellular environment, digest and display peptides on their surface, and then present these peptides to immune cells that can execute the response. The intercellular trafficking of immune regulating proteins, such as the major histocompatibility complexes (MHC) [28], by exosomes has the potential to either stimulate or block the immune response, dependent on the exosomal contents [17]. Uptake of exosomes plays an important role in B cell and DC cell proliferation, protein presentation, and interactions with other immune cells [17].
\nB cells perform multiple functions as an immune cell, including presenting antigens to T cells in order to stimulate additional immune responses. B cells traditionally operate though clathrin-mediated endocytosis, relying heavily on the B-cell receptor [60]. However, when it comes to exosome internalization, B cells have shown a greater dependence on lipid rafts and various receptors, such as adhesion molecules and tetraspanins [17] than on clathrin, indicating a preference for clathrin-independent and receptor-mediated endocytosis (Figure 2B). In analyzing B cell uptake of exosomes, using the mantle cell lymphoma (mutated immature B cell) cell line, Jeko-1, Hazan-Halevy et al., found dynamin, epidermal growth factor receptor (EGFR), and cholesterol to be involved in exosome internalization instead of clathrin [61]. EGFR is a well-established target in cancer therapy, particularly with lung cancer [62] and its role in exosome internalization may lend clarity and power to multiple existing and future chemotherapeutics. Additional exosomal surface proteins, with receptor functions, have been identified as participants in B cell internalization of TEX, including integrins (CD49) and cell adhesion molecules (intercellular adhesion molecule 1—ICAM-1/CD54 and CD62L) [17].
\nThese protein interactions between the cell and the exosomal membranes are essential steps in the influence the exosome has on the recipient cell. Exosomes derived from myeloma cells, cancerous plasma (mature B) cells, are dependent on the interaction between exosomal fibronectin and cellular heparan sulfate in order to form a bond between cell and exosome, resulting in modification of intracellular signaling [63]. As seen with these cells, the effects caused by the exosomes are not entirely dependent on uptake, even though the standard operation of APCs requires internalization. Some exosome-cell binding (as opposed to internalization) may be sufficient, or specifically designed, to alter intracellular processes, including signaling, as is also seen with dendritic cell-derived exosomes and T cell function [16]. While the influence of heparan sulfate on internalization in B cells is still unclear, there is evidence linking heparan sulfate proteoglycans to exosomal internalization which indicates that while it wasn’t assessed in these cells, the uptake may still be present [21, 22, 23]. Whether these differing mechanisms and protein participants of uptake in the B cell population are dependent on normal versus oncologic physiology of recipient cells, or on the origin of the exosome population (tumor-derived versus non-tumor derived) is yet to be determined.
\nThese heterogeneous protein profiles are specific to each cell type and contribute to the comparative ability of each cell to internalize exosomes. In line with the role of B cells, it was found that they readily take in exosomes, in contrast to other immune cells such as T cells and natural killer cells [61, 64]. This suggests that certain immune cells are more effective at endocytosing exosomes than others, consistent with the primary functions of these specific cell types. Additional groups have shown that while B cells internalize exosomes, the uptake is significantly less than that of macrophages and dendritic cells, but similar to T cells [17]. This was shown in non-mutated mouse cells and may also illustrate important differences between cancer cell and normal cell internalization mechanisms.
\nDendritic cells (DC) can be classified as both APCs and as phagocytes since internalization of extracellular material is a crucial part of their role in the immune system. Endocytosis pathways involved in exosome uptake in these cells have been tested with various endocytic blockers, including cytochalasin D (inhibits actin polymerization), EDTA (chelates calcium), and decreased temperature (reducing active cellular processes) [15, 37, 65, 66]. As dendritic cells mature, their mode of endocytosis changes; starting first with macropinocytosis, and then in the mature cell, receptor-mediated endocytosis and phagocytosis prevails [67] (Figure 2C). Despite the evidence of phagocytosis in mature DCs, it was demonstrated that immature DCs are more adept at exosomal uptake [37, 68]. Developmental preference for exosome uptake may shed light on why cancer cells, which often have similar profiles to developing cells and are subject to continuous proliferation, are so responsive to modification by exosomes. Also, immature DCs play a role in immunologic tolerance and so are less likely to activate T cells, while mature DCs activate T cell immunity [15]. This down-regulation of the adaptive immune response by immature DCs would be advantageous for tumors and so TEX may specifically target immature DCs, explaining the increase in uptake. While the mechanism is still unknown, dendritic cells are also more likely to take up TEX or DC-derived exosomes than B and T cells, as seen with fluorescent staining
Many of the studies of exosome internalization by DCs have revealed dependence on various adhesion molecules. The ubiquity of these proteins on exosomes, leukocytes, and endothelial cells promotes the non-specific internalization characteristic of DCs. The involvement of ICAM-1 and/or its ligand, lymphocyte function-associated antigen (LFA-1), in DC-exosome interaction has been shown both
In addition to binding to membrane receptors, dendritic cell endocytosis is dependent on lipid rafts and the lipid components of the cell membrane, particularly with viral or bacterial uptake [73, 74]. As viruses and exosomes are similar in size, endocytosis mechanisms are often common between these two structures [22]. Lipid-dependent endocytosis is evident in exosome uptake by DCs as illustrated with DC- and T-cell derived exosomes [15, 75]. While proteins have been the most common structure analyzed in connection with exosomal uptake, the membrane cholesterol concentration of recipient cells [15] as well as the lipid profile of the exosomal membrane [75] both play a role in uptake of exosomes by dendritic cells and need further clarification.
\nIn addition to the previously mentioned cells, two other circulating cells/structures have also been found to endocytose exosomes, platelets and T cells. Platelets are cell fragments involved in blood coagulation that are unique in their formation as they are devoid of a nucleus and some organelles. Despite a reduced intracellular load, they are involved in binding extracellular vesicles. They do so through the interaction of cellular P-selectin and vesicular P-selectin glycoprotein ligand-1 (PSGL-1) as well as PS [72]. Data suggests that binding facilitates fusion of the exosomes to the platelets, transferring of material and enhancing platelet coagulation activity [72]. This speaks to the impact of these exosomes on intracellular communication, both in the variability and specificity of recipient cells, since binding and fusion occurred preferentially in the activated platelets [72] (Figure 3A). The exosomes in this study came from monocytes, suggesting this interaction could be a key player in coagulation at a site of injury.
\nCell-specific internalization of exosomes: (A) Platelet-exosome interactions have been linked to fusion as well as the binding to PSGL-1 and phosphatidylserine, (B) T cell are influenced through their surface interactions with exosomes.
T cells are the effector cells of the immune system and intercellular communication is essential for activation. Endocytosis, while not a primary function of T cells, is important to T cell receptor signaling [76] as well as other functions. Dynamin-dependent endocytosis [76], phagocytosis [77], and RME [78] are some of the mechanisms involved in T cell interaction with its surrounding environment. In relation to exosomes, T cells operate through RME [17, 79, 80] and lipid raft-dependent endocytosis [75]. However, T cells do not always readily uptake exosomes as was found in a comparison with other blood cell types. In a peripheral blood mononuclear cell culture, when uptake by monocytes was blocked, internalization by T-cells increased [47], suggesting that T cell uptake may be an adaptive response to increased exosome concentration. When exosome uptake was compared to multiple splenic leukocytes [15] or peripheral blood leukocytes [64], T cells showed minimal internalization. T cell activity is often regulated by surface interactions with other cells, such as with the T cell receptor and the MHC II/antigen interaction with APCs. Exosomal influence on T cells may therefore operate similarly with surface interaction instead of exosome internalization (Figure 3B). When cultured with DC or DC-derived exosomes, T cells acquired functional surface molecules including MHC II from exosomes through direct exosome interaction with the T cell membrane, while still showing little evidence of internalization [81]. Mouse T cells do not express MHC II and after incubation with these exosomes, this protein was identified on the surface of the T cell, suggesting the binding of exosomes to cellular membranes is sufficient to transfer material, without internalization [81]. Further research into the transfer of material between exosomes and immune cells may elucidate the role exosomes play in immune regulation in the tumor microenvironment. Depending on the cell type involved, exosome-mediated communication and manipulation may not be entirely dependent on endocytosis.
\nEpithelial and endothelial cells are responsible for lining most of the organs, spaces, and blood vessels in the body. They are in a prime position to be exposed to and actively endocytose a wide variety of extracellular material. Due to this broad selection, the specific mechanisms utilized are dependent on the cell subtype as well as the character of the endocytosed material [82, 83, 84]. With such variability, it is no surprise that exosome uptake by epithelial and endothelial cells is just as diverse (Figure 4). Cellular location of these cells is crucial in cancer biology as most of the TEX will be in close proximity to epithelial and endothelial cells either in the circulatory system or during paracrine spread in solid tumors. While there have been many studies on cell-exosome interaction in these cells, there is still much work needed to clearly understand all of the factors that dictate the endocytic mechanism of epithelial and endothelial cells from different tissues.
\nCell-specific internalization of exosomes: (A) epithelial and (B) endothelial cells. Epithelial cells and endothelial cells show the most diversity in exosome uptake of all the cell types. Multiple receptor involved in the internalization process are expressed on both cell types, including tetraspanins, adhesion molecules, and heparan sulfate peptidoglycans (HSPG). Intercellular adhesion molecule 1 (ICAM-1).
A unique finding in exosome studies with epithelial and endothelial cells is the dependence of uptake on intracellular signaling. Svensson et al., discovered that exosome internalization is dependent on the proper functioning of the signaling pathway, ERK1/2-HSP27 [43]. The promotion of endocytosis through intracellular signaling has been shown previously with EGFR-cSrc-ERK1/2 pathways in epithelial cells [85] and the Ras-PI3K pathway with virus uptake by fibroblasts [86]. However, little is known about how these pathways facilitate exosome internalization. The ability of exosomes to cross the blood–brain barrier and be endocytosed by the microvascular endothelial cells in the brain is also dependent on signaling. Tumor necrosis factor (TNFα) signaling, as is seen in stroke models, enhances exosome uptake [87]. Intracellular signaling may provide a regulatory mechanism to control exosome internalization. Some studies described previously have shown that fusion of exosomes to the cell membrane, without endocytosis, can influence intracellular signaling [63], but these are the first to show how intracellular signaling specifically impacts the endocytosis mechanism of exosomes. These results illustrate the complexity of exosome-cell interactions and where additional research is needed. The interdependence of exosome-cell interactions and intracellular signaling are unexplored areas with vast therapeutic potential and are necessary to better understand how extracellular vesicles influence their environment.
\nOther characteristics are influential in directing endocytosis in epithelial cells including vesicle size, lipid profile, and protein profile (Figure 4A). In epithelial cells, particle size dictates entry mechanism with macropinocytosis as one of the pathways operative at a size range that corresponds with exosomes [88]. This pattern is supported by multiple studies where exosome internalization was decreased when key aspects of macropinocytosis were targeted. Macropinocytosis was blocked with an inhibitor of Na+/H+ exchange (which affects Rac1 activation and actin reorganization) in human cerebral microvascular endothelial cells (hCMEC/D3) [89] and HeLa cells, as well as with an inhibitor of phosphoinositide 3-kinase (PI3K) (influences membrane ruffling and macropinosome formation) [19, 90] with concomitant decreases in exosome internalization. Assessing the same pathway but from an activating instead of inhibiting direction, exosome internalization was stimulated by activation of epidermal growth factor receptor (which activates Rac family members) in HeLa cells [19]. Membrane extensions, or filopodia, that facilitate the formation of the macropinosome and are regulated by Rac1 activation have also been shown to influence exosome internalization in hepatocyte (Huh7) and kidney (Hek293) cells [91], furthering the support that exosomes utilize macropinocytosis in multiple epithelial cell lines.
\nThe lipid profile of the exosomes and membrane integrity of the cell are also important contributors to vesicle uptake in several different types of epithelial and endothelial cells. While macrophages readily recognize external-facing PS, these cells can also utilize exosomal PS in the process of internalization, as was shown when pre-incubating exosomes with Annexin V inhibited uptake by HeLa cells (cervical cancer epithelial cells), A375 and A431 cells (squamous skin cancer cells) [92] and in human umbilical vein endothelial cells (HUVEC) [93]. Disruption of cellular lipid raft integrity through cholesterol depletion or sequestration reduced exosome uptake in U87 human glioblastoma epithelial cells [43], hCME/D3 human cerebral microvascular cells [89], HeLa cells [43, 90], HUVECs [43, 46], and A375 cells [46]. Lipid rafts play a key role in many of the functions of epithelial cells, including the protein binding interactions between cell and extracellular environment. Also, some of the most central components to epithelial cell function are proteins that interact closely with the environment such as integrins and adhesion molecules, and are anchored into lipid rafts.
\nProtein interactions are essential to epithelial and endothelial function and are closely tied to several of the most common endocytosis pathways used by these cells. Clathrin-dependent endocytosis has been shown in gastric [94], nasopharyngeal [95], breast [96], ovarian cancer epithelial cells [97] and HUVECs [98]. Caveolin-dependence was seen in breast [96] and nasopharyngeal cancer [95], however, caveolin-1 showed negative regulation in glioblastoma cell lines [43] (Figure 4B). General receptor-mediated uptake has been shown with several proteins including heparan sulfate peptidoglycan (HSPG) in glioblastoma cells and HUVECs [99, 100] and in the transitional epithelial cells of the bladder [101]; intercellular adhesion molecule (ICAM1) in hCMEC/D3 cells [89], rat aortic endothelial cells [48], and HUVECs [102]; lectins in cervical cancer [103], HUVECs [102], rat aortic endothelial cells [48] and hCMEC/D3 cells [89]; cad-11 in prostate cancer [104]; syncytin proteins in choriocarcinoma [105] and tetraspanins in an
The extracellular matrix (ECM) and stroma are important contributors to cellular homeostasis and function. This is particularly evident in tumors when evaluating the role of the tumor microenvironment (TME) on the survival and progression of the tumor cells. Fibroblasts are the major component of this extracellular environment. In normal physiology, they promote stromal stability, while in cancer, they contribute to altered ECM, increased angiogenesis, and metastasis [108]. These cells are in a pivotal position to interact with circulating exosomes and their internalization can have a compounding effect on the surrounding environment. Fibroblasts have been shown to participate primarily in clathrin-mediated endocytosis [109, 110] and occasionally receptor-mediated endocytosis [111]. Interestingly, RME [48, 106] and macropinocytosis [91] are the mechanisms by which fibroblasts have been shown to internalize exosomes (Figure 5). Tetraspanins are important proteins in fibroblast function and migration [112]. This protein family is well represented on the exosomal surface and is key to the uptake in many different cell types [48]. Additionally, evidence shows that the smaller the size of the vesicle, the more likely the fibroblast is to use receptors to internalize particles [111]. These three qualities lend support to the evidence of RME as a key pathway for fibroblasts to endocytose exosomes.
\nCell-specific internalization of exosomes: fibroblasts. Fibroblasts take up exosomes with tetraspanins and utilize multiple endocytic pathways.
The nervous system is a uniquely isolated environment with limited connection to the systemic circulation. This characteristic has long impeded therapeutic delivery for brain pathologies. The potential of exosome transport, however, is particularly poignant, as exosomes have been observed selectively targeting neurons and glial cells, successfully crossing the blood brain barrier [113]. Improving our understanding of endocytosis mechanisms involved in these particular cells is essential to therapeutic progression. Clathrin-mediated endocytosis is the most commonly observed pathway with exosomal trafficking between neurons and glial cells [114, 115]. However, some neurons also utilize macropinocytosis [114] and specific receptors, such as SNAP25 (a SNARE family protein) [116], to take up exosomes (Figure 6). Microglia performs phagocytosis similar to their counterparts in the extra-neuronal environment [117]. Using exosomes from two different sources, Chivet et al., illustrated the specificity of exosome targeting seen elsewhere in the body, is also evident in the nervous system. Exosomes from a neuroblastoma cell line (N2a) were preferentially internalized by astrocytes and oligodendrocytes, whereas exosomes from cortical neurons were primarily taken up by hippocampal neurons [118]. It was also shown that pre-synaptic regions were the primary site of internalization of these exosomes [118]. Endocytosis is an important process in the pre-synaptic membrane to recycle released synaptic vesicles [119], indicating that the exosomes may capitalize on this constitutive process for entrance to the neuron. Whether exosomes primarily utilize the specific clathrin-mediated endocytosis in this region [119] or are simply taken by chance with the constant bulk endocytosis [120] still remains unclear. Exosome uptake is a developing area of neuro-research, but with significant potential for therapeutics, it is growing rapidly.
\nCell-specific internalization of exosomes: neurons. Neurons use similar pathways but receptor/ligand binding has less variability. Synaptosomal associated protein 25 (SNAP25).
Exosomes are internalized by a multitude of cell types and play an important role in cellular physiology. Our grasp of the mechanisms of this internalization is growing as we are better able to identify characteristics of the cell and the vesicles that facilitate uptake. Pathologic states, such as cancer, have played an integral role in our understanding of how the cellular-exosomal interaction proceeds. Clarity is still needed to better understand the mechanisms by which exosome internalization is so varied from cell to cell and within the same cell. As we have seen with fibroblasts, the vesicle size can dictate mechanism of uptake [111]. The presence or abundance of specific proteins such as scavenger receptors on macrophages [46, 47, 48] and lipid profiles in several types of cells, such as external-facing phosphatidylserine [20, 48, 49, 56] all contribute to the specificity of uptake. As has been discussed, cell type can dictate uptake mechanism, particularly with phagocytic cells and professional antigen presenting cells, but even within these specialized cells, differing mechanisms occur regularly and further evaluation is needed to parse the primary determinants.
\nVarious types of endocytosis have been identified as possible mechanisms of intercellular transport of exosomal contents to include macropinocytosis [19, 56, 114], phagocytosis [20], clathrin-mediated [52, 114], caveolin-dependent [95], lipid raft-dependent [43, 46], and clathrin- /caveolin-independent [61] endocytosis. Though much about these processes is unique, there are some aspects where functional overlap exists between them. Macropinocytosis is a form of endocytosis that consists of membrane ruffles forming intracellular vesicles to internalize large amounts of extracellular fluid [30]. This varies from other forms of endocytosis in its formation of separate and distinct intracellular vesicles (macropinosomes) and the internalization of material that is considered non-specific exosomal has been recorded in microglia [56], human epidermoid carcinoma-derived A431 cells stimulated by endothelial growth factor receptor (EGFR) and by the pancreatic cancer MiaPaCa-2 cell line [19]. Macropinocytosis is not selective in which molecules are internalized from the extracellular environment, and so uptake may be dictated simply by proximity to the cells and not targeted by the exosome specifically [121]. However, it has been shown that some exosomes naturally induce macropinocytosis internalization [90] and others, through manipulation of exosomal content, can selectively activate this mechanism in order to increase uptake [122]. Phagocytosis is a much more common method of taking up exosomes, especially with phagocytic cells of the immune system. Feng et al., showed that two leukemia cell lines, K562 and MT4, solely utilized phagocytosis for exosome internalization [20, 121].
\nFour other general categories of endocytosis focus on specific cellular proteins that facilitate the uptake of particles. Clathrin and caveolin are both cytosolic proteins that form specific pits with which to internalize various substances [25]. The exact reasons why and when a cell uses clathrin, caveolin, or neither, is still incompletely understood but particle size and cell type seem to play a role [43, 115, 121]. Caveolin-dependent endocytosis is important in albumin uptake, cholesterol transport, and intracellular signaling. Due to the small size of the caveolae, its endocytosed material tends to be smaller than 60 nm [25]. Clathrin-dependent mechanisms however can internalize particles up to 120 nm. The size restrictions may indicate, with further investigation into which uptake mechanism is utilized by which cells, a possible functional difference between vesicle sizes within the current exosome size range [121]. The clathrin-dependent process is involved in many different cell types and functions ranging from vesicle recycling in the neuronal synapse to organ development and ion homeostasis [25]. Many of the common, well-known endocytosis receptors utilize clathrin coated pits, such as low-density lipoprotein receptor (LDLR) and transferrin receptor (TfR). One of the most commonly used ways to determine which of these mechanisms is in operation is through inhibitory drugs or knocking down certain key players [121]. Dynamin, a GTPase, facilitates the fission of the intracellular clathrin coated vesicle [25, 123]. Dynasore, an inhibitor of dynamin, has been utilized to effectively block endocytosis of extracellular vesicles and establish clathrin-mediated endocytosis as a mechanism of uptake for these vesicles [21, 52, 56]. Following siRNA downregulation of caveolin-1 (the primary protein involved in caveolae-dependent endocytosis), exosome internalization was significantly reduced in B cells [95, 121]. Inhibitory drugs have also been useful in the determination of a third mechanism, lipid-raft mediated endocytosis. The lipid raft is a small portion of the plasma membrane, rich in sphingolipids and sterols, that facilitates various cellular processes [124]. Use of methyl-β-cyclodextrin (MβCD), which alters the cholesterol content of the membrane and disrupts lipid rafts, has been seen by several groups to impair exosomal internalization [43, 44, 97]. While lipid raft-dependent endocytosis is the primary clathrin- and caveolae-independent mechanism, other pathways and independent interactions have been described in the internalization of exosomes [61, 124]. Endocytosis is the primary method of exosomal delivery of its contents but research is still needed to understand what determines the specific mechanism whether it is cell type, exosome type, or condition specific [121].
\nExosome stability, ubiquitous presence, and influential contents make them ideal candidates for therapeutic modalities in a wide variety of pathologies. The significance of exosomal contribution to the cellular network throughout the body still carries untapped potential for conquering some of the most pressing current health challenges including cancer and neurodegeneration. Understanding how these exosomes interact with and enter the myriad of cells in the body will empower our ability to capitalize on this natural social network.
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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Egypt",slug:"an-updated-seismic-source-model-for-egypt",totalDownloads:3414,totalCrossrefCites:11,totalDimensionsCites:21,abstract:null,book:{id:"4488",slug:"earthquake-engineering-from-engineering-seismology-to-optimal-seismic-design-of-engineering-structures",title:"Earthquake Engineering",fullTitle:"Earthquake Engineering - From Engineering Seismology to Optimal Seismic Design of Engineering Structures"},signatures:"R. Sawires, J.A. Peláez, R.E. Fat-Helbary, H.A. Ibrahim and M.T. García\nHernández",authors:[{id:"77194",title:"Dr.",name:"José",middleName:"A.",surname:"Peláez",slug:"jose-pelaez",fullName:"José Peláez"},{id:"171273",title:"Dr.",name:"Rashad",middleName:null,surname:"Sawires",slug:"rashad-sawires",fullName:"Rashad Sawires"},{id:"171274",title:"Dr.",name:"María Teresa",middleName:null,surname:"García Hernández",slug:"maria-teresa-garcia-hernandez",fullName:"María Teresa García Hernández"},{id:"171275",title:"Dr.",name:"Raafat El-Shafey",middleName:null,surname:"Fat-Helbary",slug:"raafat-el-shafey-fat-helbary",fullName:"Raafat El-Shafey Fat-Helbary"},{id:"171276",title:"Dr.",name:"Hamza Ahmed",middleName:null,surname:"Ibrahim",slug:"hamza-ahmed-ibrahim",fullName:"Hamza Ahmed Ibrahim"}]},{id:"47961",doi:"10.5772/59641",title:"Seismic Reliability-Based Design Optimization of Reinforced Concrete Structures Including Soil-Structure Interaction Effects",slug:"seismic-reliability-based-design-optimization-of-reinforced-concrete-structures-including-soil-struc",totalDownloads:1339,totalCrossrefCites:4,totalDimensionsCites:10,abstract:null,book:{id:"4488",slug:"earthquake-engineering-from-engineering-seismology-to-optimal-seismic-design-of-engineering-structures",title:"Earthquake Engineering",fullTitle:"Earthquake Engineering - From Engineering Seismology to Optimal Seismic Design of Engineering Structures"},signatures:"Mohsen Khatibinia, Sadjad Gharehbaghi and Abbas Moustafa",authors:[{id:"94191",title:"Prof.",name:"Abbas",middleName:null,surname:"Moustafa",slug:"abbas-moustafa",fullName:"Abbas Moustafa"},{id:"173876",title:"Dr.",name:"Sadjad",middleName:null,surname:"Gharehbaghi",slug:"sadjad-gharehbaghi",fullName:"Sadjad Gharehbaghi"}]},{id:"67102",doi:"10.5772/intechopen.85322",title:"Impacts of the 2015 Gorkha Earthquake: Lessons Learnt from Nepal",slug:"impacts-of-the-2015-gorkha-earthquake-lessons-learnt-from-nepal",totalDownloads:2249,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Nepal is highly vulnerable to a number of disasters for example: earthquakes, floods, landslides, fires, epidemics, avalanches, windstorms, hailstorms, lightning, glacier lake outburst floods, droughts and dangerous weather events. Among these disasters—earthquake is the most- scary and damaging. The effects of a disaster, whether natural or human induced, are often long lasting. The Gorkha earthquake of 25 April 2015 enormously affected human, socio-economic and other multiple sectors and left deep scars mainly in the economy, livelihood and infrastructure of the country. Besides the natural factors, the damages from disasters in Nepal are in increasing trend due to the human activities and inadequate proactive legislations. Fundamentally, the weak structures have been found as the major cause of damage in earthquakes. This underlines the need for strict compliance of building codes. Thus, proactive disaster management legislation focusing on disaster preparedness is necessary. This paper analyses and shows the critical gaps and responsible factors that would contribute towards seismic risk reduction to enable various stakeholders to enhance seismic safety in Nepal. Additionally, this chapter aims to pinpoint the deficiencies in disaster management system in Nepal with reference to the devastating Gorkha earthquake and suggest appropriate policy and advanced technical measures for improvement.",book:{id:"7660",slug:"earthquakes-impact-community-vulnerability-and-resilience",title:"Earthquakes",fullTitle:"Earthquakes - Impact, Community Vulnerability and Resilience"},signatures:"Shiva Subedi and Meen Bahadur Poudyal Chhetri",authors:[{id:"285969",title:"Mr.",name:"Shiva",middleName:null,surname:"Subedi",slug:"shiva-subedi",fullName:"Shiva Subedi"},{id:"293220",title:"Dr.",name:"Meen",middleName:null,surname:"Paudyal Chhetri",slug:"meen-paudyal-chhetri",fullName:"Meen Paudyal Chhetri"}]},{id:"60778",doi:"10.5772/intechopen.76014",title:"The Earthquake Disaster Risk in Japan and Iran and the Necessity of Dynamic Learning from Large Earthquake Disasters over Time",slug:"the-earthquake-disaster-risk-in-japan-and-iran-and-the-necessity-of-dynamic-learning-from-large-eart",totalDownloads:1102,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"This book chapter targets how learning from large earthquakes disasters occurred and developed in Japan and Iran in the last 100 years. As research case studies, large earthquake disasters in Japan and Iran were investigated and analyzed. Normal distribution was found to be a good estimate of the magnitude distribution for earthquakes, in both the countries. In Japan, there is almost a linear correlation between magnitude of earthquakes and number of dead people. However, such correlation is not present for Iran. This lack of correlation in Iran and existence of linear correlation in Japan highlights that the magnitude of earthquakes directly affects the number of fatalities and extent of destruction in Japan, while in Iran, there is an increased complexity with regard to the factors affecting earthquake consequences. A correlation is suggested between earthquake culture and learning from large earthquake disasters in both Japan and Iran. Learning from large earthquake disasters is impacted by a multitude of factors, but the rhythm of learning in Japan is much higher if compared with Iran. For both Japan and Iran, a reactive learning approach based on past earthquake disasters needs to be constantly backed up by a proactive approach and dynamic learning.",book:{id:"6564",slug:"earthquakes-forecast-prognosis-and-earthquake-resistant-construction",title:"Earthquakes",fullTitle:"Earthquakes - Forecast, Prognosis and Earthquake Resistant Construction"},signatures:"Michaela Ibrion and Nicola Paltrinieri",authors:[{id:"209369",title:"Ph.D.",name:"Michaela",middleName:null,surname:"Ibrion",slug:"michaela-ibrion",fullName:"Michaela Ibrion"},{id:"244752",title:"Dr.",name:"Nicola",middleName:null,surname:"Paltrinieri",slug:"nicola-paltrinieri",fullName:"Nicola Paltrinieri"}]},{id:"28219",doi:"10.5772/28044",title:"Recent Landslide Damming Events and Their Hazard Mitigation Strategies",slug:"recent-landslide-damming-events-and-their-hazard-mitigation-strategies",totalDownloads:2232,totalCrossrefCites:4,totalDimensionsCites:6,abstract:null,book:{id:"2049",slug:"advances-in-geotechnical-earthquake-engineering-soil-liquefaction-and-seismic-safety-of-dams-and-monuments",title:"Advances in Geotechnical Earthquake Engineering",fullTitle:"Advances in Geotechnical Earthquake Engineering - Soil Liquefaction and Seismic Safety of Dams and Monuments"},signatures:"Ahsan Sattar and Kazuo Konagai",authors:[{id:"72541",title:"MSc.",name:"Ahsan",middleName:null,surname:"Sattar",slug:"ahsan-sattar",fullName:"Ahsan Sattar"},{id:"121222",title:"Prof.",name:"Kazuo",middleName:null,surname:"Konagai",slug:"kazuo-konagai",fullName:"Kazuo Konagai"}]}],mostDownloadedChaptersLast30Days:[{id:"47538",title:"An Updated Seismic Source Model for Egypt",slug:"an-updated-seismic-source-model-for-egypt",totalDownloads:3414,totalCrossrefCites:11,totalDimensionsCites:21,abstract:null,book:{id:"4488",slug:"earthquake-engineering-from-engineering-seismology-to-optimal-seismic-design-of-engineering-structures",title:"Earthquake Engineering",fullTitle:"Earthquake Engineering - From Engineering Seismology to Optimal Seismic Design of Engineering Structures"},signatures:"R. Sawires, J.A. Peláez, R.E. Fat-Helbary, H.A. Ibrahim and M.T. García\nHernández",authors:[{id:"77194",title:"Dr.",name:"José",middleName:"A.",surname:"Peláez",slug:"jose-pelaez",fullName:"José Peláez"},{id:"171273",title:"Dr.",name:"Rashad",middleName:null,surname:"Sawires",slug:"rashad-sawires",fullName:"Rashad Sawires"},{id:"171274",title:"Dr.",name:"María Teresa",middleName:null,surname:"García Hernández",slug:"maria-teresa-garcia-hernandez",fullName:"María Teresa García Hernández"},{id:"171275",title:"Dr.",name:"Raafat El-Shafey",middleName:null,surname:"Fat-Helbary",slug:"raafat-el-shafey-fat-helbary",fullName:"Raafat El-Shafey Fat-Helbary"},{id:"171276",title:"Dr.",name:"Hamza Ahmed",middleName:null,surname:"Ibrahim",slug:"hamza-ahmed-ibrahim",fullName:"Hamza Ahmed Ibrahim"}]},{id:"47738",title:"Earthquakes and Dams",slug:"earthquakes-and-dams",totalDownloads:3261,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"4488",slug:"earthquake-engineering-from-engineering-seismology-to-optimal-seismic-design-of-engineering-structures",title:"Earthquake Engineering",fullTitle:"Earthquake Engineering - From Engineering Seismology to Optimal Seismic Design of Engineering Structures"},signatures:"Hasan Tosun",authors:[{id:"79083",title:"Dr.",name:"Hasan",middleName:null,surname:"Tosun",slug:"hasan-tosun",fullName:"Hasan Tosun"}]},{id:"47881",title:"Simplified Multi-Block Constitutive Model Predicting the Seismic Displacement of Saturated Sands along Slip Surfaces with Strain Softening",slug:"simplified-multi-block-constitutive-model-predicting-the-seismic-displacement-of-saturated-sands-alo",totalDownloads:1163,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"4488",slug:"earthquake-engineering-from-engineering-seismology-to-optimal-seismic-design-of-engineering-structures",title:"Earthquake Engineering",fullTitle:"Earthquake Engineering - From Engineering Seismology to Optimal Seismic Design of Engineering Structures"},signatures:"Constantine A. Stamatopoulos",authors:[{id:"171228",title:"Dr.",name:"Constantine",middleName:null,surname:"Stamatopoulos",slug:"constantine-stamatopoulos",fullName:"Constantine Stamatopoulos"}]},{id:"67102",title:"Impacts of the 2015 Gorkha Earthquake: Lessons Learnt from Nepal",slug:"impacts-of-the-2015-gorkha-earthquake-lessons-learnt-from-nepal",totalDownloads:2248,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Nepal is highly vulnerable to a number of disasters for example: earthquakes, floods, landslides, fires, epidemics, avalanches, windstorms, hailstorms, lightning, glacier lake outburst floods, droughts and dangerous weather events. Among these disasters—earthquake is the most- scary and damaging. The effects of a disaster, whether natural or human induced, are often long lasting. The Gorkha earthquake of 25 April 2015 enormously affected human, socio-economic and other multiple sectors and left deep scars mainly in the economy, livelihood and infrastructure of the country. Besides the natural factors, the damages from disasters in Nepal are in increasing trend due to the human activities and inadequate proactive legislations. Fundamentally, the weak structures have been found as the major cause of damage in earthquakes. This underlines the need for strict compliance of building codes. Thus, proactive disaster management legislation focusing on disaster preparedness is necessary. This paper analyses and shows the critical gaps and responsible factors that would contribute towards seismic risk reduction to enable various stakeholders to enhance seismic safety in Nepal. Additionally, this chapter aims to pinpoint the deficiencies in disaster management system in Nepal with reference to the devastating Gorkha earthquake and suggest appropriate policy and advanced technical measures for improvement.",book:{id:"7660",slug:"earthquakes-impact-community-vulnerability-and-resilience",title:"Earthquakes",fullTitle:"Earthquakes - Impact, Community Vulnerability and Resilience"},signatures:"Shiva Subedi and Meen Bahadur Poudyal Chhetri",authors:[{id:"285969",title:"Mr.",name:"Shiva",middleName:null,surname:"Subedi",slug:"shiva-subedi",fullName:"Shiva Subedi"},{id:"293220",title:"Dr.",name:"Meen",middleName:null,surname:"Paudyal Chhetri",slug:"meen-paudyal-chhetri",fullName:"Meen Paudyal Chhetri"}]},{id:"63029",title:"An Estimation of “Energy” Magnitude Associated with a Possible Lithosphere-Atmosphere-Ionosphere Electromagnetic Coupling Before the Wenchuan MS8.0 Earthquake",slug:"an-estimation-of-energy-magnitude-associated-with-a-possible-lithosphere-atmosphere-ionosphere-elect",totalDownloads:1161,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"A large scale of abnormities from ground-based electromagnetic parameters to ionospheric parameters has been recorded during the Wenchuan MS8.0 earthquake. All these results present different anomalous periods, but there seems one common climax leading to a lithosphere-atmosphere-ionosphere electromagnetic coupling (LAIEC) right on May 9, 3 days prior to the Wenchuan main shock. Based on the electron-hole theory, this chapter attempts to estimate the “energy source” magnitude driving this obvious coupling with the Wenchuan focus zone parameters considered. The simulation results show that the total surface charges fall in ~107–108 C, and the related upward electric field is ~108–109 V/m. These corresponding parameters are up to 109 C and 1010 V/m when the main rupture happens, and the order of the output current is up to 107 A. The electric field increasing in the interface between the Earth’s surface and the atmosphere, on one hand, can cause electromagnetic parameter abnormities of ground-based observation, with the range beyond 1000 km. On the other hand, it can accumulate air ionization above pre-earthquake zone and lead to ionospheric anomaly recorded by some spatial seismic monitoring satellites.",book:{id:"6564",slug:"earthquakes-forecast-prognosis-and-earthquake-resistant-construction",title:"Earthquakes",fullTitle:"Earthquakes - Forecast, Prognosis and Earthquake Resistant Construction"},signatures:"Mei Li, Wenxin Kong, Chong Yue, Shu Song, Chen Yu, Tao Xie and\nXian Lu",authors:[{id:"236284",title:"Dr.",name:"Mei",middleName:null,surname:"Li",slug:"mei-li",fullName:"Mei Li"},{id:"243785",title:"MSc.",name:"Chen",middleName:null,surname:"Yu",slug:"chen-yu",fullName:"Chen Yu"},{id:"243786",title:"MSc.",name:"Chong",middleName:null,surname:"Yue",slug:"chong-yue",fullName:"Chong Yue"},{id:"243788",title:"Dr.",name:"Tao",middleName:null,surname:"Xie",slug:"tao-xie",fullName:"Tao Xie"},{id:"243789",title:"MSc.",name:"Wenxin",middleName:null,surname:"Kong",slug:"wenxin-kong",fullName:"Wenxin Kong"},{id:"243790",title:"BSc.",name:"Shu",middleName:null,surname:"Song",slug:"shu-song",fullName:"Shu Song"}]}],onlineFirstChaptersFilter:{topicId:"778",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). 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Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,annualVolume:11419,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,annualVolume:11420,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,annualVolume:11421,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:20,paginationItems:[{id:"83065",title:"Interventions and Practical Approaches to Reduce the Burden of Malaria on School-Aged Children",doi:"10.5772/intechopen.106469",signatures:"Andrew Macnab",slug:"interventions-and-practical-approaches-to-reduce-the-burden-of-malaria-on-school-aged-children",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Andrew",surname:"Macnab"}],book:{title:"Malaria - Recent Advances, and New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11576.jpg",subseries:{id:"5",title:"Parasitic Infectious Diseases"}}},{id:"82804",title:"Psychiatric Problems in HIV Care",doi:"10.5772/intechopen.106077",signatures:"Seggane Musisi and Noeline Nakasujja",slug:"psychiatric-problems-in-hiv-care",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Future Opportunities and Tools for Emerging Challenges for HIV/AIDS Control",coverURL:"https://cdn.intechopen.com/books/images_new/11575.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"82827",title:"Epidemiology and Control of Schistosomiasis",doi:"10.5772/intechopen.105170",signatures:"Célestin Kyambikwa Bisangamo",slug:"epidemiology-and-control-of-schistosomiasis",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"New Horizons for Schistosomiasis Research",coverURL:"https://cdn.intechopen.com/books/images_new/10829.jpg",subseries:{id:"5",title:"Parasitic Infectious Diseases"}}},{id:"82817",title:"Perspective Chapter: Microfluidic Technologies for On-Site Detection and Quantification of Infectious Diseases - The Experience with SARS-CoV-2/COVID-19",doi:"10.5772/intechopen.105950",signatures:"Andres Escobar and Chang-qing Xu",slug:"perspective-chapter-microfluidic-technologies-for-on-site-detection-and-quantification-of-infectious",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"SARS-CoV-2 Variants - Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}}]},overviewPagePublishedBooks:{paginationCount:13,paginationItems:[{type:"book",id:"6667",title:"Influenza",subtitle:"Therapeutics and Challenges",coverURL:"https://cdn.intechopen.com/books/images_new/6667.jpg",slug:"influenza-therapeutics-and-challenges",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Shailendra K. 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He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}]},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}]},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. 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In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"117248",title:"Dr.",name:"Andrew",middleName:null,surname:"Macnab",slug:"andrew-macnab",fullName:"Andrew Macnab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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