\r\n\t(i) Quantum dots of very high-quality optical applications, Quantum dot light-emitting diodes (QD-LED) and ‘QD-White LED’, Quantum dot photodetectors (QDPs), Quantum dot solar cells (Photovoltaics).
\r\n
\r\n\t(ii) Quantum Computing (quantum bits or ‘qubits’), (vii) The Future of Quantum Dots (broad range of real-time applications, magnetic quantum dots & graphene quantum dots), Superconducting Loop, Quantum Entanglement, Quantum Fingerprints.
\r\n
\r\n\t(iii) Biomedical and Environmental Applications (to study intracellular processes, tumor targeting, in vivo observation of cell trafficking, diagnostics and cellular imaging at high resolutions), Bioconjugation, Cell Imaging, Photoelectrochemical Immunosensor, Membranes and Bacterial Cells, Resonance Energy-Transfer Processes, Evaluation of Drinking Water Quality, Water and Wastewater Treatment, Pollutant Control.
",isbn:"978-1-80356-594-1",printIsbn:"978-1-80356-593-4",pdfIsbn:"978-1-80356-595-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"0dd5611c62c91569bd2819e68852002a",bookSignature:"Prof. Jagannathan Thirumalai",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11756.jpg",keywords:"LED, Organic LEDs, Dyes & Pigments, Solar Cells, Laser Photonics, Electronic Switching Devices, Qubits, Josephson Junction, Bioconjugation, Cell Imaging, Photoelectrochemical Immunosensor, Membranes, and Bacterial Cells",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 16th 2022",dateEndSecondStepPublish:"May 27th 2022",dateEndThirdStepPublish:"July 26th 2022",dateEndFourthStepPublish:"October 14th 2022",dateEndFifthStepPublish:"December 13th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"15 hours",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. J. Thirumalai received his Ph.D. from Alagappa University, Karaikudi, He was also awarded the Post-doctoral Fellowship from Pohang University of Science and Technology (POSTECH), the Republic of Korea. His research interests focus on luminescence, self-assembled nanomaterials, and thin-film optoelectronic devices. He has published more than 60 SCOPUS/ISI indexed papers and 11 book chapters, edited 4 books, and member of several national and international societies like RSC, OSA, etc. His h-index is 19.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"99242",title:"Prof.",name:"Jagannathan",middleName:null,surname:"Thirumalai",slug:"jagannathan-thirumalai",fullName:"Jagannathan Thirumalai",profilePictureURL:"https://mts.intechopen.com/storage/users/99242/images/system/99242.png",biography:"Dr. J. Thirumalai received his Ph.D. from Alagappa University, Karaikudi in 2010. He was also awarded the Post-doctoral Fellowship from Pohang University of Science and Technology (POSTECH), Republic of Korea, in 2013. He worked as Assistant Professor of Physics, B.S. Abdur Rahman University, Chennai, India (2011 to 2016). Currently, he is working as Senior Assistant Professor of Physics, Srinivasa Ramanujan Centre, SASTRA Deemed University, Kumbakonam (T.N.), India. His research interests focus on luminescence, self-assembled nanomaterials, and thin film opto-electronic devices. He has published more than 60 SCOPUS/ISI indexed papers and 11 book chapters, edited 4 books and member in several national and international societies like RSC, OSA, etc. Currently, he served as a principal investigator for a funded project towards the application of luminescence based thin film opto-electronic devices, funded by the Science and Engineering Research Board (SERB), India. 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\n\t\t\t
1. Introduction
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Carbon nanotubes are typically considered as molecular-scale tubes of graphitic carbon. Depending on numbers of carbon layers, they are categorized as single-walled and multi-walled nanotubes (Zhao & Stoddart, 2009). The unique structure provides nanotubes with extraordinary mechanical and electrical properties, e.g., tensile strength up to 63 Gpa (Harris, 2004) and theoretically carrying electrical current density of 1,000 times higher than copper (Hong & Myung, 2007). Nanotubes have been extensively investigated with publication over 50,000 (searched from Web of Science) in recent ten years, and have been proposed for various applications in the fields of chemistry, physics, and engineering (Feldman et al., 2008; Guldi et al., 2005; Liu et al., 2009; \n\t\t\t\t\t\n\t\t\t\t\t\tPeng et al., 2008\n\t\t\t\t\t\n\t\t\t\ta; Shi, 2009).
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Although nanotubes are very promising in a wide variety of fields, the large-scale applications of individual nanotubes remain challenging due to the difficulty in structure control, existence of impurities, and poor processability (Karousis et al., 2010). In order to improve their practical applications, bulk nanotube materials have recently attracted increasing attentions, particularly, by formation of composites with polymers (Moniruzzaman & Winey, 2006; \n\t\t\t\t\t\n\t\t\t\t\t\tPeng, 2008\n\t\t\t\t\t\n\t\t\t\tb). Here nanotubes may provide good mechanical, electrical, and thermal properties, while polymers enable them with high flexibility, low cost, and easy fabrication. Three typical methods, i.e., solution blending, melt blending, and in situ polymerization, have been widely explored (Moniruzzaman & Winey, 2006). Unfortunately, a common and critical challenge is yet to be solved, i.e., randomly dispersed nanotubes in polymer matrices (see Figure 1) (\n\t\t\t\t\t\n\t\t\t\t\t\tPeng, 2008\n\t\t\t\t\t\n\t\t\t\tb). As a result, the prepared composites could not fully take advantage of the exceptional properties of individual nanotubes. For instance, we found that a nanotube/poly(methyl methacrylate) composite showed low tensile strength and electrical conductivity of 10−100 MPa and 10-6−10-1 S/cm, respectively.
Schematic illustration for the random aggregation of nanotubes in nanotube/polymer composites synthesized by traditional approaches. Reproduced with permission from Reference (\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tPeng, 2008\n\t\t\t\t\t\t\t\n\t\t\t\t\t\tb). Copyright 2008, American Chemical Society.
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investigated. However, alignment of nanotubes still needs to be improved, and properties of composites are not as good as expected. Recently, an effective approach has been developed by the use of nanotube arrays, sheets, and fibers with highly aligned nanotubes as building blocks to synthesize composite materials. Successful systems have been extensively reported by us and other groups. This chapter describes recent progress in aligned nanotube/polymer materials with excellent mechanical, electrical, and sensing properties.
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For the convenience of readers, the basic synthesis and characterization of nanotube arrays, sheets, and fibers which are crucial to fabricate high-quality composites are first discussed in this chapter. Then the main efforts are paid to the preparation of aligned nanotube/polymer arrays, films, and fibers with emphasis on the improved mechanical, electrical, and sensing properties.
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2. Aligned carbon nanotubes in forms of arrays, sheets, and fibers
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2.1. Carbon nanotube arrays
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Nanotube arrays are typically synthesized through a chemical vapor deposition process in which the catalytic metal (e.g., Fe, Co, or Ni) film on SiO2/Si wafer form nanoparticles at high temperature to assist nanotube growth. High-efficiency catalysts are critical to grow high-quality aligned nanotube arrays. Iron possibly represents the most studied catalyst system (Fan et al., 1999). For the traditional direct coating of iron film on SiO2/Si wafer, the iron layer generally becomes inactive within several minutes of nanotube growth due to its inter-diffusion with the substrate and accumulation of amorphous carbon. In order to grow longer nanotube arrays, catalyst precursors were continuously added to the system to nucleate new catalyst nanoparticles during the growth, however, the arrays were often composed of several stacked layers of nanotubes. In addition, the nanotubes grown in this way were often accompanied by excessive catalyst particles and amorphous carbon.
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Recently, a new approach was reported, in which a thin Al2O3 layer was introduced between the catalyst and substrate to efficiently improve the growth of nanotubes (Li et al., 2006). The dense buffer layer enhances the Fe wettability during the preparation of catalyst. In addition, the Al2O3 layer functions as a buffer to prevent the inter-diffusion between Fe and substrate, and further improves the formation of stable catalyst nanoparticles during the nanotube growth.
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For the Fe/Al2O3 catalyst system, the thickness uniformity of the Fe film is critical to grow good nanotube arrays. As compared in Figure 2, for the catalyst of Fe (thickness of 1 nm)/Al2O3 (thickness of 10 nm) under the same experimental conditions, the non-uniform Fe film melted to form polydisperse nanoparticles from which no nanotube array was grown (Figure 2a), while the uniform Fe film produced monodisperse nanoparticles which assisted the growth of long nanotube array (Figure 2b). The sizes of nanoparticles may be qualitatively controlled by the thickness of Fe film, which typically ranges from 0.2 to 1 nm. The resulting nanotubes are mainly multi-walled with diameters from 7 to 50 nm.
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Figure 2.
The influence of the uniformity of Fe film on growth of aligned nanotube arrays. (a) Scanning electron microscopy (SEM) image of grown nanotubes by the use of non-uniform Fe film. (b) SEM image of grown nanotubes by the use of uniform Fe film. The thickness of the used Fe film was the same of 1 nm.
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In a typical synthesis, the growth is fast (e.g., ~ 60 μm/min) in the first 20 min; afterwards, the growth gradually slows down and was normally terminated at 90 min. The growing rate also depends on the synthetic temperature. Zhu et al. had investigated a temperature range of 730−780º C, and found that the growing rates increased with increasing temperatures, e.g., 46 μm/min at 730º C, 64 μm/min at 750º C, and 74 μm/min at 780º C (Li, Q. et al., 2006). Water vapor, a weak oxidant, also greatly affected the growth of nanotubes in a more complex behavior. Introduction of water vapor did not obviously promote the growth of nanotubes at a lower temperature range of 730 to 750º C. In contrast, it significantly increased the growing rates of nanotubes at a higher temperature range from 750 to 780º C. In addition, water vapor had been found to prolong the growth time from 90 to 120 min, which produced longer nanotubes.
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In order to further improve the production of nanotube arrays, an approach based on continuously moving substrates has been developed during chemical vapor deposition processes. As shown in Figure 3, the Fe/Al2O3 catalyst on Si substrate was fed continuously into the growth zone of the furnace through a moving stage driven by external motor, and nanotube arrays were then realized to be produced at large scale (de Villoria et al. 2009). Currently, the nanotube arrays could be grown at moving speeds of substrates up to 2.4 mm/s. No obvious differences had been observed for the resulting nanotube arrays between static and moving growth models.
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Figure 3.
a) Schematic illustration of the continuous feeding of the catalyst. (b) Schematic construction of the synthetic system. Reproduced with permission from Reference (de Villoria et al., 2009). Copyright 2009, IOP Publishing.
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2.2. Carbon nanotube sheets
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A general and efficient route of preparing aligned nanotube sheets is to directly spin them out of the above array. Figure 4a schematically shows the formation of nanotube sheet spun from an array. Figure 4 b and 4c further show scanning electron microscopy images of nanotube sheets in which nanotubes are highly aligned along the spinning direction as required. The measured areal sheet density was 2.7 μg/cm2 and the volumetric density was 1.5 μg/cm3. The density of nanotube sheet can be further improved, e.g., 0.5 g/cm3, simply by immersing them into a liquid along the nanotube-aligned direction and then taking them out (Zhang, M. et al., 2005).
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It should be noted that most nanotube arrays are not spinnable. In order to investigate their spinnability, nanotube arrays grown with increasing growth times from 10 to 180 min were first compared as model materials (Huynh & Hawkins, 2010; Sun & Peng, unpublished results). It was found that the prolonged growth time dramatically decreased the spinnability of the arrays, and the arrays grown longer than 30 min did not show good spinnability. For instance, long sheets up to meters were spun from the arrays grown in 15 min; sheets with length of centimeters were spun from the arrays grown in 40 min as the sheets easily broke during the spinning process; even worse, only short clumps were pulled out of the arrays grown in 180 min. The morphologies of the arrays were studied by scanning electron microscopy (Sun & Peng, unpublished results). The nanotube array shows very clean surfaces at growth times below 30 min. With the increase of growth time, a disordered layer was observed at the top of the arrays. The thickness of this layer increased with increasing growth time. Figure 5 compares the top and side views of arrays synthesized with different growth times of 15 and 90 min. The array grown in 15 min is clean without aggregates, while a lot of flake-like carbon aggregates are found at the top of the nanotube array grown in 90 min. These flakes are randomly piled, and their sizes decrease with increasing growth times. The flakes severely hinder the spinnability of synthesized arrays.
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Besides growth time, the other experimental conditions including substrate, temperature, gas flow rate, and catalyst as well as its pre-treatment are also critical for synthesis of spinnable nanotubes. Huynh et al. and Zhang et al. had systematically investigated the effects of above variables that influence the spinnability of nanotubes, respectively(Huynh,2010; Zhang, Y. et al.; 2010). However, there is no simple reason or key factor for nanotube spinnability. In addition, although the surface morphology and alignment of nanotube arrays had been demonstrated to be very important for their spinnability, no unique characteristic is found to obviously distinguish a spinnable from a non-spinnable array. It was shown that nanotube arrays could be spinnable or not for a wide variety of height (80-900 μm) with nanotube diameters ranging from 7 to 11 nm and areal densities across an order of magnitude.
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Figure 4.
Fabrication of nanotube sheets by a direct spinning method. (a) A schematic illustration. (b) SEM image for the formation of nanotube sheet from an array. Reproduced with permission from Reference 21. Copyright 2005, American Association for the Advancement of Science. (c) SEM image of a nanotube sheet. Reproduced with permission from Reference (\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tPeng, 2008\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\tb). Copyright 2008, American Chemical Society.
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Although it is difficult to fully understand the mechanism of nanotube spinnability currently, two possible models had been suggested by Fan et al. and Baughman et al., respectively (Zhang, M. et al., 2004; Zhang, X. et al., 2006). Fan and co-workers proposed that the unique features of spinnable nanotube arrays lied in that the nanotubes had very clean surfaces, and consequently there were strong van der Waals interactions among them (Zhang, X. et al., 2006). When nanotubes were pulled out of the arrays, it was the van der Waals force that made the nanotubes to join end to end to form a continuous sheet. Baughman and co-workers claimed that the spinnability was due to the disordered region at the top and bottom of the nanotube array, which entangled together forming a loop (Zhang, M. et al., 2004, 2005). The above mechanisms had been demonstrated to work for specific arrays. However, as spinnable nanotube arrays greatly vary for different systems or even for the same systems, it remains challenging to draw general conclusions.
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Figure 5.
Typical SEM images of (a) the spinnable nanotube array by side view, (b) the spinnable nanotube array by top view, (c) the non-spinnable nanotube array by side view, and (d) the non-spinnable nanotube array by top view.
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2.3. Carbon nanotube fibers
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Similar to nanotube sheets, nanotube fibers are mainly spun from nanotube arrays (Zhang, M. et al., 2004). Figures 6 a and 6b show the formation of a fiber by twisting the nanotube sheet pulled out of an array. This spinning process can be easily scaled up to produce long nanotube fibers. The diameters of nanotube fibers can be controlled from 2 to 30 μm by tuning the initial ribbon width which is defined as a bunch of nanotubes pulled out of an array at the beginning of the spinning.
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Although nanotube fibers are generally spun from aligned nanotube arrays, they had been also fabricated from nanotube cottons in which nanotubes were randomly arranged on substrates (Zheng et al., 2007). The cotton was composed of low-density nanotubes with length of centimeters and diameter of 100-380 nm, and these ultra-long nanotubes were entangled to form continuous fibers. The other methods, e.g., wet spinning of nanotube dispersions (Zhang, M. et al., 2004) and direct spinning from chemical vapor deposition reactions(Ericson et al.; 2004), had been also developed to fabricate nanotube fibers. Figure 6c shows a spool of 30-m
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Figure 6.
a) and (b) SEM images of a nanotube fiber spun out of an array. Reproduced with permission from Reference (Zhang, M. et al., 2004). Copyright 2004, American Association for the Advancement of Science. (c) A 30-m spool of nanotube fiber fabricated by a solution spinning process. Reproduced with permission from Reference (Ericson et al., 2004). Copyright 2004, American Association for the Advancement of Science.
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nanotube fiber wound on a spindle via a solution spinning process (Ericson et al.; 2004).
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Nanotube fibers showed much higher density of ~ 0.8 g/cm3 compared with nanotube sheets (Zhang, M. et al., 2004). The linear density is typically 10 μg/m compared with 10 mg/m and 20-100 mg/m for cotton and wool yarns, respectively. That is, about a million of nanotubes pass through the cross section of a fiber with diameter of 5 μm. As nanotubes are tightly bundled together inside, nanotube fibers had shown excellent mechanical and electrical properties, e.g., high tensile strengths and electrical conductivities.
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In general, the tensile strength of a twisted fiber can be described by the equation of δf/δnanotube ≈ cosα[1 − (kcosec α)], where δf and δnanotube are the tensile strengths of the fiber and the nanotube, respectively; α is the twist angle; and k = (dQ/μ)1/2/3L with d of the nanotube diameter, L of the nanotube length, μ of the friction coefficient among nanotubes, and Q of the nanotube migration length (Li, Y. L. et al., 2004). Therefore, the fiber strength increases with increasing nanotube length and decreasing nanotube diameter. For instance, the nanotube fibers spun from arrays of 300, 500, and 650 μm in thickness showed tensile strengths of 0.32, 0.56, and 0.85 GPa, respectively (Li, Y. L. et al., 2004); the diameter of spinnable nanotubes typically ranges from 7 to 11 nm. Post-spin twisting can also improve their tensile strengths with larger twist angle and higher density of building nanotubes. For instance, the twist angle of outer nanotubes increased from 10o to 21o; the density of nanotubes increased two times with decreasing fiber diameter from 10 to 7 μm, and the closer contact among nanotubes enhanced their van der Waals forces and frictions with better load transfers. Similarly, a solution treatment can also increase the fiber densities with improved tensile strengths. Zhu and co-workers reported that the specific strength of nanotube fiber could be 5.3 times the specific strength of the strongest commercial carbon fiber (T1000), and the specific stiffness of nanotube fiber could be 4.3 times the specific stiffness of the stiffest commercial carbon fiber (M70J) (Zhang, X. et al., 2007). Windle and co-workers further increased the tensile strength of nanotube fiber to ~9.6 GPa (Koziol et al., 2007). Figure 7 compares the specific strength and specific stiffness of the above nanotube fibers (the elliptical area at the top left corner of the graph) with other high-performance engineering fibers.
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Figure 7.
Comparison of the specific strength and specific stiffness of nanotube fibers versus the properties of other commercially available high-performance fibers. Reproduced with permission from Reference (Koziol et al., 2007). Copyright 2007, American Association for the Advancement of Science.
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Nanotube fibers showed excellent electrical conductivities up to 103 S/cm at room temperature. Figure 8a further indicates the temperature dependence of a nanotube fiber’s conductivities measured by a four-probe method. The conductivity increases with the increase of the temperature, suggesting a semiconducting behavior. For the temperature dependence of conductivity, two main mechanisms had been suggested, i.e. variable range hopping mechanism and tunneling conduction mechanism (Li, Q. et al., 2007; \n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeng et al., 2008\n\t\t\t\t\t\t\n\t\t\t\t\tc). A systematic comparing study showed that the conduction in nanotube fibers was mainly controlled by the hopping mechanism. In more detail, the relationship between conductivity and temperature in hopping model can be also expressed as σ ∝ exp (-A/T[1/(d+1)]), where A is a constant and d is the dimensionality. The plots of lnσ vs. T-1/4 (for d=3), T-1/3 (for d=2) and T-1/2 (for d=1) show decreasing linear fitting coefficients (Figures 8b,\n\t\t\t\t\t8c, and 8d), which suggests that the electron transport is more consistent with a three-dimensional hopping mechanism. This behavior is most likely due to the defect structures of nanotubes and a lot of contacting points among neighboring short nanotubes in fibers. Therefore, electrons cannot be confined in the one-dimensional channel along the nanotube-aligned direction. Instead, electrons hop from one localized site to another, or possibly from a nanotube to another.
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Figure 8.
Electrical properties of a nanotube fiber. (a) Temperature dependence of the conductivity measured by a four-probe method. (b) Three-dimensional hopping conduction model by plot of lnσ vs. T-1/4. (c) Two-dimensional hopping conduction model by plot of lnσ vs. T-1/3. (d) One-dimensional hopping conduction model by plot of lnσ vs. T-1/2.
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The electrical properties of nanotube fibers largely depend on structural changes of nanotubes. Therefore, their conductivities can be tuned by different chemical treatments. Oxidization on their surfaces increased the fiber’s conductivities by introduction of acceptor dopant groups. The covalent link of metal nanoparticles onto nanotubes also enhanced the fiber’s conductivities through an increase of carrier density. However, annealing of nanotube fiber in forming gas (94% Ar and 6% H2) significantly lowered their conductivity due to the formation of sp3 carbon bonds (Li, Q. et al., 2007).
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3. Aligned carbon nanotube/polymer composites
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3.1. Preparation of aligned carbon nanotube/polymer composites
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The structures of aligned nanotube/polymer composites in the forms of arrays, films, and fibers have been schematically shown in Figure 9. Polymers are incorporated into nanotubes which maintain the high alignments. These composites are mainly synthesized through the use of above pure nanotube arrays, sheets, and fibers, and the other fabrication methods will be also compared later.
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Aligned nanotube/polymer arrays are typically prepared by immersing a pure nanotube array into polymer solution, followed by evaporation of solvent (\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeng & Sun, 2009\n\t\t\t\t\t\t\n\t\t\t\t\t). For this approach, a wide variety of polymers (either plastic or conjugated polymers) may be used to fabricate composite arrays. Figure 10 compares a nanotube array before and after incorporation with polystyrene. Obviously, nanotubes maintained the high alignment in polymer matrix. Similarly, aligned nanotube/polymer composites could be also synthesized by first immersing pure nanotube arrays into monomers, followed by polymerization of monomers (Feng et al., 2003; Raravikar et al., 2005; Yang et al., 2008). Recently, porous nanotube arrays were fabricated after heating treatment of as-synthesized dense nanotube arrays or through the use of polystyrene beads (Das et al., 2009; Dionigi et al., 2007), and polymers could be incorporated into the pores to form aligned nanotube composites.
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The aligned nanotube/polymer films are produced by spin-coating or casting polymer solutions onto nanotube sheets, followed by evaporation of solvents. Film thickness may be controlled by varying concentrations of polymer solutions and coating times. After incorporation of designed polymers such as polystyrene, poly(methyl methacrylate), or sulfonated poly(ether ether ketones), the derived composite films were transparent and showed optical transparencies of higher than 80% (thickness of ~5 μm) (\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeng, 2008\n\t\t\t\t\t\t\n\t\t\t\t\tb).
Schematic illustration of the aligned nanotube/polymer composites in the forms of (a) array, (b) film, and (c) fiber.
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Figure 10.
SEM images of the aligned nanotubes (a) before and (b) after formation of composite with polystyrene. The white arrows show the aligned directions of nanotubes. Reproduced with permission from Reference ( \n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tPeng & Sun, 2009\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t). Copyright 2009, Elsevier.
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mechanical force, cutting nanotube/resin composites induced nanotubes on the surface to align along the cutting direction (Kimura et al., 2002), or mechanical stretching of nanotube/polyhydroxyaminoether composites at high temperature aligned nanotubes in polymer matrix (Kimura et al., 2002). For the synthesis of aligned nanotube/polymer composites by magnetic field, monomers in nanotube solutions were polymerized in a mold under magnetic field (Kimura et al., 2002). Alignment of nanotubes was based on their anisotropic nature. Alignment of nanotubes in bulk epoxy matrix was available by application of electrical field, where nanotube/epoxy composites were prepared by a layer-by-layer method (Zhu et al., 2009). Alignment of nanotubes was due to polarization of their high aspect ratios under electrical field. However, composites by these methods show relatively low alignments of nanotubes compared to the use of nanotube arrays or sheets. The alignment of nanotubes may be assessed by microscopy technology, X-ray diffraction, and polarized Raman spectroscopy.
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Aligned nanotube/polymer fibers can be directly prepared by physical attachment or chemical reaction of polymers onto nanotubes in pure nanotube fibers. To improve the uniformity of polymers, monomers may be first incorporated into nanotube fibers followed by polymerization as monomers can penetrate into much smaller voids in nanotube fibers and form more uniform composites through solution processes. For instance, high-quality nanotube/polydiacetylene composite fibers were produced by the physical attachment of diacetylenic monomers followed by topochemical polymerization of diacetylenic moieties under UV light (\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeng et al., 2009\n\t\t\t\t\t\t\n\t\t\t\t\t).
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Another widely explored method to aligned nanotube/polymer fibers is electrospinning, an electrostatically induced self-assembly process where nanoscale fibers were typically produced (Baji et al., 2010; Ge et al., 2004; Go et al., 2004; Kang et al., 2009). The surface tension, jet elongation, and slow relaxation of nanotubes contribute to orientation of nanotubes. Some other approaches including coagulation-based spinning (Razal et al., 2007; Vigolo et al., 2000& 2002), melting spinning (Haggenmueller et al., 2003), dip coating method through microfluidic phenomena (Jang et al., 2009), and orientation by external stimuli such as mechanical interaction (Ji et al., 2009) had been also developed to synthesize aligned nanotube/polymer fibers. However, similar to the composite arrays and films, the nanotube alignments in the resulting composite fibers are much lower compared to the direct use of pure nanotube fibers.
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3.2. Improved mechanical, electrical, and sensing properties of aligned carbon nanotube/polymer composites
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The alignment of nanotubes has greatly improved the mechanical properties of their polymer composites. Figure 11 compares the tensile strengths of less aligned nanotube/polymer fibers and aligned nanotube/polymer fibers. The nanotube/polymer fibers at Figure 11a were fabricated through a melting spinning process, i.e., the melting nanotube/nylon 6 mixtures were pressurized through a spinneret to form composite fibers (Gao et al., 2005). The nanotube/nylon 6 fibers showed relatively low strengths of less than 100 MPa. In contrast, the aligned nanotube/polymer fibers exhibited the strength of higher than 1000 MPa (Figure 11b).
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Figure 11.
Comparison of the mechanical strengths for (a) non-aligned nanotube/polymer fibers and (b) aligned nanotube/polymer fibers. Reproduced with permission from Reference (Gao et al., 2005). Copyright 2005, American Chemical Society.
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The alignment of nanotubes has also greatly improved the electrical properties of their polymer composites. Figure 12 summarizes and compares the conductivities of randomly dispersed nanotube/polymer composites and aligned nanotube/polymer composites in forms of arrays, films, and fibers (\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeng et al., 2008\n\t\t\t\t\t\t\n\t\t\t\t\ta, 2008b, 2008c; Peng & Sun, 2009). The non-aligned nanotube/polymer composites (including arrays, films, and fibers) fabricated through traditional solution blending or melt blending generally show conductivities lower than 10-1 S/cm at room temperature. As a comparison, the aligned nanotube/polymer arrays, films, and fibers show conductivities of 1-100 S/cm, 10-200 S/cm, and 102-103 S/cm at room temperature, respectively. The aligned nanotube/polymer composites followed a three-dimensional hopping conduction mechanism, which can be important for some optoelectronic applications (\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeng et al., 2009\n\t\t\t\t\t\t\n\t\t\t\t\t).
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The improved mechanical and electrical properties of above aligned nanotube/polymer composite have been realized through the direct use of nanotube arrays, sheets, and fibers. In the case of other approaches to align nanotubes (Baji et al., 2010; Ge et al., 2004; Go et al., 2004; Haggenmueller et al., 2003; Jang et al., 2009; Ji et al., 2009; Kang et al., 2009; Razal et al., 2007; Vigolo et al., 2000, 2002), similar improvements were also observed. For instance, aligned nanotube/polyacrylonitrile fibers after hot-stretching treatment showed a significant enhancement of tensile strength by 320.7% (Ji et al., 2009), while aligned nanotube/epoxy arrays induced by electric field could improve electrical conductivities by four orders of magnitude in the direction of alignment (Zhu, Y. et al., 2009). However, possibly due to the relatively low degree of alignment, both strengths and conductivities were much lower compared with the direct use of aligned nanotube materials, e.g., strength below 325 MPa and conductivity of 10-10−10-8 S/cm at room temperature for the discussed nanotube/polyacrylonitrile fibers and nanotube/epoxy arrays, respectively.
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Orientation factor had been already used to quantitatively characterize the alignment degree of nanotubes through Herman’s equation of f = (3<cos2θ>–1)/2, where θ is the average angle between the nanotube and the aligned direction determined by Raman spectroscopy (Ge et al., 2004). However, the orientation factors were only available in very limited studies. Therefore, it remains difficult to quantitatively compare the experimental results (e.g., strengths and conductivities) of nanotube/polymer composites among different methods or different lab.
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Figure 12.
Comparison of the electrical conductivities for (a) non-aligned nanotube/polymer composites, (b) aligned nanotube/polymer arrays, (c) aligned nanotube/polymer films, and (d) aligned nanotube/polymer fibers.
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Nanotubes show the gas sensing capabilities through the changes of resistances after gas sorption. However, the use of non-aligned nanotubes for the sensing detection often needs tedious fabrication processes to integrate single nanotubes into sensors, and the number of analytes is also largely limited. In contrast, aligned nanotubes do not need direct manipulation of individual nanotubes. Particularly, the resistance changes of individual nanotubes could be greatly amplified as millions of nanotubes were collectively addressed through a common electrode (Lin et al., 2003; Wei et al., 2006; Zhu, Z. et al., 2010). For instance, Wei et al. reported that aligned nanotube/poly(vinyl acetate) arrays showed high sensitivity and good selectivity to a wide variety of chemical vapors such as tetrahydrofuran, ethanol, and cyclohexane (Wei et al., 2006). The similar improvements at sensing capabilities after the nanotube alignment had been also observed for detections of the glucose and other biosensing applications (Lin et al., 2003; Zhu, Z. et al., 2010).
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As previously discussed, the aligned nanotube/polymer composites show a semiconducting behavior with three-dimensional hopping conduction mechanism. This electrical property provides composites with other unexpected sensing properties. For instance, polydiacetylene is well known to change colors under external stimuli such as temperature, pH, solvent, and mechanical stress, mainly due to the conformation change of the conjugated backbone (Peng et al., 2007; \n\t\t\t\t\t\tSun et al., 2010\n\t\t\t\t\ta, 2010b). By incorporation of polydiacetylene into aligned nanotube fibers, polydiacetylene was first realized to rapidly and reversibly change colors under electrical current, typically from blue to red (Figure 13) (\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeng et al., 2009\n\t\t\t\t\t\t\n\t\t\t\t\t). The capability of forming strong electrical fields among aligned nanotubes was believed to induce the conformation change of incorporated polydiacetylene with the chromatic transition.
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Figure 13.
Chromatic transitions of nanotube/polydiacetylene fibers in response to electric current. (a) Schematic illustration of experimental setups for current-induced chromatism. (b) Rapid and reversible electrochromatism. Reproduced with permission from Reference (\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tPeng et al., 2009\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t). Copyright 2009, Nature Publishing Group.
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4. Conclusion
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This chapter has mainly described the realization and importance of alignment of nanotubes in their polymer composites. Three typical forms of composites including arrays, films, and fibers are fabricated through the use of nanotube arrays, sheets, and fibers, respectively. The aligned nanotube composites have exhibited much improved mechanical, electrical, and sensing properties compared with those without alignment of nanotubes. The aligned nanotube/polymer composites may show promising applications in a wide variety of fields, particularly as high-end components for aerospace, energy, and other structural and optoelectronic materials.
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Despite the great progresses having been made on fabrications, characterizations, and properties of aligned nanotube/polymer composites, here we also hope to call attention to a few key unmet challenges on further developing this new family of functional materials in the future.
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Firstly, increasing attentions should be paid to establishing quantitative relationships between the alignment degrees of nanotubes and the properties (e.g., strengths and conductivities) of the composites. Therefore, it becomes available to accurately compare different fabrication approaches and different composite systems, which may provide important and general clues to improve the composite properties.
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Secondly, most nanotube arrays are not spinnable, and more efforts are required to understand and control the spinnability of nanotube arrays to fabricate high-performance composite films and fibers. For instance, the mechanical and electrical properties of aligned nanotube/polymer composites strongly depend on the length of nanotubes. The longer the nanotubes, the better are the properties of composites. However, spinnable nanotube arrays range from 80 to 900 μm in height, and higher arrays are typically not spinnable. For the spinnability of nanotube arrays, another crucial issue is related to the nanotube alignment. It had been qualitatively shown that a high alignment of nanotubes was required for their spinnability (Sun & Peng, Unpublished results; Zhang, M. et al., 2005). However, as no quantitative characterizations have been made for the alignment degrees of nanotubes in arrays, it remains unclear for an accurate relationship between the alignment and spinnability of nanotube arrays.
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Thirdly, polymers are mainly incorporated into aligned nanotubes through non-covalent interactions, and very few studies can be found to connect polymers and nanotubes by chemical bonds. Nevertheless, compared to physical attachment, polymers can be more uniformly incorporated into nanotubes by chemical modifications, and the resulting composites show more excellent properties, e.g., improved mechanical strengths as polymers cross-link neighboring nanotubes. Of course, some other issues such as uniformity in the composite and repeatability of the fabrication are also important for the development of aligned nanotube/polymer composites, particularly for their practical applications.
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Acknowledgments
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This work was supported by Natural National Science Foundation of China (20904006, 91027025), Science and Technology Commission of Shanghai Municipality (1052nm01600, 09PJ1401100), Program for New Century Excellent Talents in University (NCET-09-0318), Ministry of Education of China, and Program for Key Discipline Creativity Talents at Fudan University.
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\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/16998.pdf",chapterXML:"https://mts.intechopen.com/source/xml/16998.xml",downloadPdfUrl:"/chapter/pdf-download/16998",previewPdfUrl:"/chapter/pdf-preview/16998",totalDownloads:4156,totalViews:275,totalCrossrefCites:2,totalDimensionsCites:2,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:61,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"October 18th 2010",dateReviewed:"January 27th 2011",datePrePublished:null,datePublished:"August 17th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/16998",risUrl:"/chapter/ris/16998",book:{id:"467",slug:"carbon-nanotubes-polymer-nanocomposites"},signatures:"Huisheng Peng, Xuemei Sun and Tao Chen",authors:[{id:"26920",title:"Prof.",name:"Huisheng",middleName:null,surname:"Peng",fullName:"Huisheng Peng",slug:"huisheng-peng",email:"penghs2004@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"27007",title:"Dr.",name:"Xuemei",middleName:null,surname:"Sun",fullName:"Xuemei Sun",slug:"xuemei-sun",email:"082044015@fudan.edu.cn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"27008",title:"Dr.",name:"Tao",middleName:null,surname:"Chen",fullName:"Tao Chen",slug:"tao-chen",email:"taochenm@163.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Aligned carbon nanotubes in forms of arrays, sheets, and fibers",level:"1"},{id:"sec_2_2",title:"2.1. Carbon nanotube arrays",level:"2"},{id:"sec_3_2",title:"2.2. Carbon nanotube sheets",level:"2"},{id:"sec_4_2",title:"2.3. Carbon nanotube fibers",level:"2"},{id:"sec_6",title:"3. Aligned carbon nanotube/polymer composites",level:"1"},{id:"sec_6_2",title:"3.1. Preparation of aligned carbon nanotube/polymer composites",level:"2"},{id:"sec_7_2",title:"3.2. Improved mechanical, electrical, and sensing properties of aligned carbon nanotube/polymer composites",level:"2"},{id:"sec_9",title:"4. Conclusion",level:"1"},{id:"sec_10",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAhir\n\t\t\t\t\t\t\tS. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSquires\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTajbakhsh\n\t\t\t\t\t\t\tA. 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ACS Nano, 3\n\t\t\t\t\t8 (July 2009), 2157\n\t\t\t\t\t2162 .\n\t\t\t'},{id:"B56",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhao\n\t\t\t\t\t\t\tY. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStoddart\n\t\t\t\t\t\t\tJ. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Noncovalent Functionalization of Single-Walled Carbon Nanotubes. Acc. Chem. Res., 42\n\t\t\t\t\t8 (August 2009), 1161\n\t\t\t\t\t1171 .\n\t\t\t'},{id:"B57",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZheng\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tQ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChikkannanavar\n\t\t\t\t\t\t\tS. 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P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoratkar\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiang\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Alignment of multiwalled carbon nanotubes in bulk epoxy composites via electric field. J. Appl. Phys., 105\n\t\t\t\t\t5 (March 2009), 054319 6).\n\t\t\t'},{id:"B59",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhu\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSong\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurugapalli\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoussy\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhong\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Nano-yarn carbon nanotube fiber based enzymatic glucose biosensor. Nanotechnology, 21\n\t\t\t\t\t16 (April 2010), 165501\n\t\t\t\t\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Huisheng Peng",address:"",affiliation:'
Key Laboratory of Molecular Engineering of Polymers of Ministry of Education, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, China
Key Laboratory of Molecular Engineering of Polymers of Ministry of Education, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, China
Key Laboratory of Molecular Engineering of Polymers of Ministry of Education, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, China
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1. Introduction
Epstein-Barr virus (EBV), a ubiquitous gamma-herpesvirus, infects the vast majority of the worldwide human population. This virus was initially discovered in cultured lymphoma cells from patients with Burkitt’s lymphoma (BL) in 1964 [1]. During the primary infection, EBV infects epithelial cells of the oropharynx where it actively replicates and also infects B cells where it establishes a life-long latency in the form of an episome located in the host cell nucleus. During latency, EBV may produce nine viral latency proteins, including six so-called “Epstein-Barr Nuclear Antigens” (EBNA1, -2, -3A, -3B, -3C, and -LP), involved in transcriptional regulation, and three “Latent Membrane Proteins” (LMP1, -2A, and -2B), mimicking signals needed for B cell maturation, as well as two small noncoding RNAs (EBER-1 and EBER-2), BamHI-A rightward transcripts (BARTs), and miRNAs. Four different latency programs can be identified, based on the proteins that are expressed (Table 1). EBV primary infection, which occurs more often in childhood, is usually asymptomatic in children, whereas it may be responsible for infectious mononucleosis (IM) in teenagers or young adults in western countries. In addition to this nonmalignant disease, EBV can also be associated with diverse malignant pathologies. In particular, EBV is involved in the development of several malignancies of lymphoid origin including endemic Burkitt’s lymphoma [2], nasal NK/T lymphoma [3], some Hodgkin’s lymphoma [4], and B- or T-cell lymphoproliferations in immunocompromised patients [5]. It is also implicated in epithelial malignancies such as undifferentiated nasopharyngeal carcinoma (NPC) [6] and 10% of cases of gastric carcinoma [7]. Although populations from all geographic areas are infected by the virus, the incidence of the pathologies in which it occurs varies significantly depending on the region [8]. For example, BL occurs mainly in children living in sub-Saharan Africa [9], and the prevalence of NPC is particularly high in adults living in Southern China, Southeast Asia, and Northern Africa [10]. The differences observed in the geographic distribution of these pathologies suggest that there could be various genetic variants of EBV, of different global distributions, and with different levels of transforming capacity. This question of a specific disease variant is raised by many authors and is still being debated. In this chapter, we wish to take inventory of the state of knowledge concerning the variability observed on the most mutated genes among all EBV genes and the possible implications in human pathology.
Program
EBV expressed proteins
Active promoters
B cell type
Latency III
Growth
EBNA-1, -2, -3A, -3B, -3C, -LP
Initially Wp
Naive B cells
LMP-1, -2A-, -2B
Then Cp
LMP promoters
EBER-1 and -2p
Latency II
Default
EBNA-1
Qp, EBER-1 and -2p
LMP-1, -2A, -2B
LMP promoters
Latency I
Latency
EBNA-1
Qp, EBER-1 and -2p
Resting B cells
Latency 0
No protein or LMP-2A
LMP-2Ap
Memory B cells
Table 1.
Proteins expressed during the different latency programs.
2. Evolving knowledge of the EBV genome
The fact that the viral genome is relatively large (175 kb), that it is made up of DNA, therefore less variable than if it was an RNA genome, and that it carries repetitive regions, limited its sequencing for a long time. The first published sequences were small fragments of the B95-8 genome; then, the entire B95-8 genome was sequenced in 1984 [11]. The B95-8 strain was the first cultured EBV cell line able to secrete large amounts of viral particles into the culture medium. It was originally obtained from a spontaneous human lymphoblastoid cell line (LCL) established from a North American case of infectious mononucleosis, the 883L cell line, whose virus was used to transform lymphocytes from a cotton top marmoset. Since it was the first strain with a fully published genome, B95-8 has been extensively studied and mapped for transcripts, promoters, and open reading frames.
This first EBV whole genome sequencing was followed by others, and complete viral genome sequences of the cell lines AG876, originating from a Ghanaian case of African BL [12] and GD1, obtained from cord B cells infected with EBV from saliva of an NPC patient in Guangzhou, China [13] were published. Sequences of some genes, mainly latency genes, were also studied, especially in lines established from patients [14, 15]. B95-8, GD1, and AG876 were sequenced by conventional shotgun sequencing (Sanger’s method). The comparison of sequences obtained for various cell lines revealed the existence of two types of EBV: type 1 or A, of which B95-8 can be considered as the prototype, and type 2 or B, exemplified by AG876. The main difference between the two types concerns the EBNA2 gene, with only 70% identity at the nucleotide level and 54% identity in the protein sequence [16]. Additional variations have also been observed in the EBNA3 genes, but to a lesser extent: 10, 12, and 19% of base pair differences for EBNA3A, 3B, and 3C, respectively [17]. The comparison of viral sequences also highlighted that the B95-8 cell line has a significant 11.8 kb deletion (positions 139,724–151,554) corresponding to some of the BART miRNA genes, one of the origins of lytic replication [11], the LF2 and LF3 genes, and a part of the LF1 gene. More complete sequence comprising the B95-8 sequence supplemented with a Raji fragment at the level of deletion has been constructed. It was annotated in 2010 as RefSeq HHV4 (EBV) sequence NC_007605 and is now used as a wild-type strain reference [18].
As adaptation of the virus to in vitro culture is possible, thus generating a bias in the results, some authors have preferred to sequence the viral genome directly in samples from patients. Therefore, the sequences GD2, from a Guangzhou NPC biopsy, and HKNPC1, from a Hong Kong NPC biopsy, were published [19, 20], both using a more recent sequencing technique, “next generation sequencing” (NGS). This technology can be used directly on samples or after enrichment, which avoids artifacts due to cellular DNA. Enrichment can be achieved by PCR or cloning into F-factor plasmids, but most frequently, it is carried out using target DNA capture by hybridization. NGS delivers a wealth of information and requires extensive bioinformatic analysis. This technology has made it possible to rapidly increase the number of fully sequenced viral genomes originating from healthy subjects or patients and thus obtain more information.
3. The most variable regions of the genome
Authors who sequenced the entire viral genome and analyzed the genomic variations came to the conclusion that the latent genes harbored the highest numbers of nonsynonymous mutations [20, 21, 22, 23, 24]. For example, Liu et al. [25] compared the sequences of nine strains of EBV to GD1, of which they were most closely related, and showed that latency genes were the most mutated. In this study, latent and tegument genes were found to harbor 58.4 to 84.3% of all nonsynonymous mutations detected for each genome. Santpere et al. [26] found that latent genes were twice as mutated as lytic genes. The observation that the latent genes harbor more nucleotide diversity than lytic genes was made regardless of the type of pathology: nasopharyngeal carcinoma [20, 21], NK/T lymphoma [27], endemic Burkitt’s lymphoma [22], Hodgkin’s lymphoma [22], posttransplant lymphoproliferative disease [22], gastric carcinoma [25], lung carcinoma [23], and also strains originating from infectious mononucleosis [22] or healthy subjects [26]. Why latent genes are the most variable is not clear today. By analyzing their data according to the Yang model [28], Santpere et al. [26] showed that the lytic genes had an evolutionary constraint close to that of the host: a strong purifying selection was objectified for 11 lytic genes. However, signatures of accelerated protein evolution rates were found in coding regions related to virus attachment and entry into host cells. The latency genes, on the other hand, show a positive selection, perhaps in relation to the MHC, which can be the cause of their large diversity. Changes in amino acids (aa) often occur in immune epitopes. Amino acid changes in CD8+ epitopes were described in all latent proteins, while changes in CD4+ epitopes were shown only for EBNA1 and -2 and LMP1 and -2 [20]. However, most codons of the EBNA3 gene under positive selection are not cytotoxic T-lymphocyte epitopes: either there are epitopes not described to date or the selection relates to other functionalities. The selection of mutants may depend on a difference in immunity in relation to the geography and/or capacity of a strain to infect and persist.
4. Variability of main latency proteins
After the virus enters a host cell, the genome circularizes through recombination of the terminal repeats (TRs) located at each end of the genome to form an episome that will be chromatinized and methylated in the same way as the human genome. Latent transcription programs in B cells are due to the differential activity of epigenetically regulated promoters and take place in three successive waves. The EBNA2 and EBNA-LP, as well as BHRF1, a bcl2 homolog, are the first viral proteins to be expressed, under the dependence of Wp promoter. The two expressed EBNAs and the cellular factor recombination signal-binding protein for immunoglobulin Kappa J region (RBP-Jk) activate then the Cp promoter, which drives the expression of all of the EBNA proteins, while Wp becomes progressively hypermethylated; the transcription will gradually be under Cp control. Subsequently, LMP1, LMP2A, and LMP2B proteins are expressed due to activation of their respective promoters. During latency I or II, Qp promoter controls EBNA1 expression, and Cp methylation is responsible for the five other EBNA silencing. Methylation does not control the Qp promoter, which is switched off by binding to a repressor protein.
As previously developed, latency proteins show the most sequence variations, and among them, EBNA1, EBNA2, EBNA-LP, and LMP1 are the most mutated. The main properties of these proteins are reported in Table 2.
4.1 EBNA1
EBNA1, expressed in both latent and lytic EBV infections, was the first EBV protein detected. EBNA1, whose structure (Figure 1) and functions have largely been studied [29, 30], is a 641 aa protein. However, EBNA1 proteins frequently exhibit size variations due to differing numbers of gly-ala repeats (aa 89–325). During latency, EBNA1 is the only protein expressed in all forms of latency in proliferating cells and also in all EBV associated malignancies. EBNA1, which acts as a homodimer, is essential for initiating EBV episome replication before mitosis, once per cell cycle, and mitotic segregation of EBV episomes, thus for the maintenance of EBV episome in latently infected cells [31]. The EBNA1 DNA-binding domain is essential but not sufficient for the replication function, and the N-terminal half of EBNA1 is also required. Two EBNA1 regions (aa 8–67 and aa 325–376) are particularly important for this activity, and the point mutations G81 or G425 enhance EBNA1-dependent DNA replication. Inversely, the EBNA1 aa 395–450 region mediates an interaction with the human ubiquitin-specific protease, USP7, which may negatively regulate replication. The partitioning of EBV episomes in two dividing cells requires two viral components: the ori P FR element and EBNA1, mainly the central Gly-Arg region aa 325–376 and secondarily the aa 8–67 sequence. EBNA1 also activates the expression of other latency genes participating in immortalization: the regions involved are the central Gly-Arg sequence and the 61–89 region. Interaction with the recognition sites located on FR, DS of ori P, and Bam-HI-Q takes place through binding sites located in the C-terminal of EBNA1 (aa 459-607), sequence which also mediates the dimerization of EBNA1 (aa 504–604). Through its interaction with both human casein kinase CK2 (aa 383–395) and cellular ubiquitin-specific protease USP7 (aa 442–448), EBNA1 is also able to disrupt promyelocytic leukemia protein (PML) bodies and degrade PML. In addition to its role in latent infection, EBNA1 can therefore participate in lytic infection by overcoming suppression by PML proteins [32]. Indeed, PML proteins and nuclear bodies were found to suppress lytic infection by EBV. Recently [33], organization in an oligomeric hexameric ring form was described for the EBNA1 DNA-binding domain, the oligomeric interface pivoting around residue T585. Mutations occurring on this residue had both positive and negative effects on EBNA1-dependent DNA replication and episome maintenance.
Figure 1.
Schematic representation of basic structure of EBNA1 protein with the different motifs and their position. Gly-Arg: region rich in Gly-Arg; Gly-Ala: Gly-Ala repeats; CK2: interaction with human casein kinase, CK2; USP7: interaction with the human ubiquitin specific protease, USP7; DNA binding: DNA-binding domain; Dimerization: region that mediates the dimerization of EBNA1. The different mutations discussed are noted.
Based on polymorphisms observed at 15 codons, Bhatia et al. [14] reported two strains named P (prototype) and V (variant), each having two subtypes defined by the aa at position 487 (P-ala, P-thr, V-pro, and V-leu). They detected mostly the P-thr and the V-leu variants, respectively, in African and American BL tumors, but these findings were not confirmed by another group who reported different spectra of EBNA1 subtypes according to different geographical areas in both healthy patients and BL tumors [34]. A fifth subtype, V-val, was later recognized in South-East Asia and was found to be prevalent in NPC samples by numerous authors [20, 35, 36, 37]. These findings suggest that the V-val variant might adapt particularly well to the nasopharyngeal epithelium or that this strain possesses an increased oncogenic potential. Indeed, most of the variant codons, localized in the DNA-binding domain, may have an impact on the EBV phenotype resulting in impaired ability to transform B-lymphocytes [30]. However, other reports observed that this subtype had no tumor-specific expression [38], and it is likely that it probably represents a dominant EBNA1 subtype in Asian regions, not found in other areas of the world [8, 23, 25]. The P-thr subtype is the most commonly observed in peripheral blood of American and African subjects as well as in African tumors. In our experience, P-thr is also the most prevalent in France and particularly in the course of lymphoproliferative diseases.
Apart from these mutations, others have been reported. For example, Borozan et al. [39] looked at gastric carcinomas and mainly found two mutations already described in NPC, H418L and A439T, located outside the DNA-binding domain and common in both NPC and GC but uncommon in other EBV isolates, from lymphomas or healthy subjects. They also described a new mutation, T85A, positioned in the region required for transcriptional activation of other latency genes and thus able to modify this function. Wang et al. [23] described the substitution T585I. T585 is subject to substitutions, and T585 polymorphism is found frequently in NPC tumors and Burkitt’s lymphoma. T585I was previously found, and this strain was defective in replication and maintenance of the viral episome [40], as well as deficient in suppressing lytic cycle gene transcription and lytic DNA replication.
In summary, EBNA1 V-val variant seems to be a geographic variant almost exclusively present in South-East Asia. Conversely, mutations T85 and T585, which occur in functional regions of the protein, could have biological consequences and especially the substitution T585I, which promotes lytic replication and is found in NPC.
4.2 EBNA2
EBNA2, a 487 aa protein, is expressed in vivo during latency III shortly after infection of B cells or in lymphomas occurring in immunocompromised patients and in LCL. As mentioned above, the variations in EBNA2 make it possible to classify EBV as types 1 and 2 (or A and B) since only 70% identity at the nucleotide level and 54% homology in the protein sequence were observed. The overall structure of the EBNA2 protein (Figure 2) is characterized by poly-P and poly-RG areas, this last one being a protein-protein and protein-nucleic acid interaction domain important for efficient cell growth transformation, and nine regions conserved throughout the gene [41]. EBNA2 acts principally as a transcription factor and contains three categories of domains critical for its transcription regulation function: transactivation domains (TAD), self-association domains (SAD), and nuclear localization signals (NLS). EBNA2 does not bind directly to DNA. It uses cell proteins as adapters to access viral or cellular enhancer and promoter sites. The C-terminal TAD (aa 448–471) is able to recruit components of basic transcriptional machinery as well as chromatin modifiers and can bind to the viral coactivator EBNA-LP, while the N-terminal TAD (aa 1–58) cannot bind EBNA-LP, although its activity can be enhanced by this protein. Two SADs (aa 1–58 and 97–121), separated by the poly-proline stretch, were identified in the N-terminal region [42]. An additional third one has been reported, localized in a nonconserved region, and flanked by the second SAD and the adapter region [43]. EBNA2 contributes to B-cell immortalization, and it has been demonstrated that type 1 EBV, which is predominantly found in EBV-associated diseases, immortalizes B cells in vitro much more efficiently than type 2 [44], which is predominantly determined by sequence variation in the C-terminus of EBNA2 [45]. During the early events of EBV infection in resting B cells, EBNA2 initiates the transcription of a cascade of primary and secondary viral and cellular target genes and therefore is responsible for the initiation of immortalization by reprogramming the resting state into a proliferative state. For this, EBNA2 interacts with chromatin remodelers and as a transcription factor cofactor [46]. Mühe et al. [47] demonstrated that the first 150 N-terminal aa of EBNA2 are important for the initiation of immortalization. EBNA2 is also involved in immortalization maintenance; the region implicated here (aa 295–378) includes the conserved regions CR5 (aa 295–307) and CR6 (aa 320–326), particularly important for this function. CR5 mediates the contact between EBNA2 and SKIP (Ski-interacting protein), and CR6 is the CBF1 (C promoter-binding factor 1) or RBP-Jk targeting domain. Mechanisms to initiate and maintain B cell immortalization are not completely understood today.
Figure 2.
Schematic representation of basic structure of EBNA2 protein with the different motifs and their position. The two transactivation domains (TADs), the three self-association domains (SADs), and the two nuclear localization signals (NLSs) are mentioned. Poly P: area rich in P; PolyRG: area rich in RG; CR5: conserved region 5, which interacts with SKIP (Ski-interacting protein); CR6: conserved region 6, which interacts with CBF1 (C promoter-binding factor 1). The different mutations discussed are mentioned.
Wang et al. [41], working on 25 EBV-associated GCs, 56 NPCs, and 32 throat washings from healthy donors in Northern China, described 4 EBNA2 subtypes according to the presence of a deletion, namely subtypes E2-A (no aa deletion), E2-B (aa 294Q deletion), E2-C (aa 357K and 358G deletion), and E2-D (aa 357K, 358G, and 294Q deletion). The E2-A subtype exhibited six nonsilent mutations, P291T, R413G, I438L, E476G, P484H, and I486T; the substitution P291T was present in six NPC E2-D and six NPC E2-C. The substitution R413G was detected in E2-C for one patient. They found that E2-A and E2-C were dominant in the samples they analyzed and that the E2-D pattern was detected only in the NPC specimens. The mutation R163M was detected in all samples. This mutation has previously been described worldwide and in different diseases.
Mutations 357 and 358 occurred in the RG domain (aa 335–362), a downregulator of EBNA2 activation of the LMP1 promoter [48]. Moreover, aa 357–363 (KGKSRDK) constitutes the PKC phosphorylation site, which can reduce the amounts of EBNA2/CBF1 complex formed. EBNA2 is suspected to be involved in the development of malignancies as a result of sequence variations most frequently affecting its regulation function.
Interestingly, EBNA2 entire-gene deletion has been shown in some endemic BL cell lines such as P3HR1, Daudi, Sav, Oku, and Ava [49]; it remains to determine if this deletion occurs classically in vivo in African BL.
In short, geographic variants were not formally demonstrated for EBNA2. Among the described mutations, the most interesting are those occurring in the PKC phosphorylation site because they can activate the Cp and/or LMP1p and thus increase the production of latency proteins.
4.3 EBNA-LP (EBNA-leader protein)
EBNA-LP, like EBNA2 and concomitantly with EBNA2, is expressed shortly after the infection of B cells in healthy individuals as well as in EBV-related malignant diseases in immunodeficient patients and LCLs. EBNA-LP acts mostly as a coactivator of the transcriptional activator EBNA2, thus inducing the expression of some cellular genes, including cyclin D2 [50], or viral genes, that is, LMP1 [51], LMP2b, and Cp and therefore having an important role in B cell immortalization. EBNA-LP also can directly interact with several cell proteins such as tumor suppressors or proteins involved in apoptosis or cell cycle regulation.
EBNA-LP is comprised of a variable number of 66 aa repetitive units, corresponding to the variable number of W1 and W2 exons located in the EBV internal repeat IR1, followed by a unique 45 aa domain, encoded by two unique 3′ exons Y1 and Y2 (Figure 3). Therefore, EBNA-LP protein may vary in size according to the number of W1–W2 repeats contained in each EBV isolate. By convention, the protein annotation is based on a single W repeat isoform (Figure 4). In this configuration, the protein has 110 aa. Conserved regions were identified in the N extremity of the protein (CR1 to CR3, respectively, aa 11–33, 45–52, and 55–62, implicated in EBNA2 binding), and in the C-terminal region (CR4 and CR5, respectively, aa 76–82 and 101–110). CR3 and a serine within W2 (S35) were demonstrated to be important for EBNA2 coactivation. EBV-mediated B cell immortalization maps to the W1W2 repeated domains and requires at least two IR1 repetitions to be effective, but a number greater than or equal to 5 is optimal [53]. Some interactions with cell proteins are mediated by the repeated W1W2 N-terminus [54]. EBNA-LP gene transcription initiates from the W promoter (Wp) residing in each IR1 repeat during the early stages of infection, and multiple EBNA-LP protein isoforms are produced. During the later stages of infection and in LCLs, transcription initiates from the C promotor (Cp) [55]. The level of transcription initiated by Cp compared to Wp varies according to different circumstances [56].
Figure 3.
Schematic representation of the IR1 region of EBV genome (according to Ref. [52]). The promoters Wp, Cp, and Qp are represented, as well as the different proteins expressed according to the stage of infection.
Figure 4.
Sequence of EBNA-LP protein, with the position of the corresponding exons opposite. Conserved regions are represented as well as the key positions. Phosphorylated serins are mentioned by an asterisk.
About 15% of BL tumors host a virus, which uses exclusively the W promoter, expressing an EBV atypical latency program [49], harboring EBNA1, EBNA3A, 3B, 3C, and a truncated form of EBNA-LP. In these cases, EBV genome lacks the EBNA2gene and the unique Y1Y2 exons of EBNA-LP. This was firstly described in P3HR1 and Daudi BL cell lines [57]. Subsequently, these cells were shown to be more resistant to apoptosis than cells infected by wild-type virus, what would be related to the truncated shape of EBNA-LP.
Given the difficulty of sequencing repetitive regions, only few authors have sequenced the IR1 region, including the EBNA-LP coding region. Previous studies identified two EBNA-LP distinct isoforms, type 1 and type 2 variants, based on the presence of G8/T12 or V8/A12 in exon W1 [58]. The Q54R substitution was also described in exon W2 from an African type 2 spontaneous lymphoblastoid cell line LCL [59]. Despite this, a high degree of conservation was reported for the Wp promoter and the W1-W2 intron, while the most diversity was observed for the BWRF1 ORF, which only shows 80% homology between various strains, and for Y exons [60]. The sequence variations in the Y exons, and especially the Y2 exon, made it possible to define four main subgroups, called A, B, C, and Z. The Akata strain belongs to subgroup A and B95-8 to subgroup B. Subgroup Z is found in type 2 EBVs, and the C subtype is characterized by V95E and V102I. Finally, it has been reported that tumor-derived strains are more prone to interstrain genetic exchange in IR1 [60].
4.4 LMP1
LMP1 is considered to be the main oncogenic protein in EBV. LMP1 is a multifunctional self-aggregating protein essential for the transformation of human B cells and rodent fibroblasts [61]. It is a 386 aa protein comprising a 24 aa cytosolic N-terminal (NT) segment, a 162 aa portion consisting of six transmembrane (TM) domains, and a 200 aa cytosolic C-terminal (CT) domain (Figure 5) [62]. The NT domain plays an important role in the orientation and anchoring of LMP1 to the membrane and its constitutive aggregation, thus contributing to the transforming function of LMP1 [63]. The TM region is involved in the localization of LMP1 at the level of lipid rafts in the membrane, thus inducing its clustering to activate signaling from the CT tail. It is remarkable that the F38LWY41 pattern in the first transmembrane fragment (TM1) and a second pattern consisting of aa W98 in TM3 are essential for the association of TM domains (1–2) with TM domains (3–6) as well as for the oligomerization and signaling of LMP1 [64]. The CT part is involved in the activation of LMP1-induced cell signaling pathways, including two important regions, CTAR1/TES1 and CTAR2/TES2 (Carboxyl-Terminal Activating Region/Transformation Effector Site) critical for EBV-mediated B-cell growth transformation [65]. Together, these regions mimic CD40, a member of the tumor necrosis factor (TNF) receptor family and key B-cell costimulatory receptor, thus enabling the recruitment of cell adapters associated with the TNF receptor family, TNF receptor-associated factors (TRAFs). The CTAR1 region includes the P204-X-Q206-X-T208 consensus pattern necessary for the attachment of TRAF adapters, specifically TRAF1, TRAF2, TRAF3, and TRAF5 [66]. Within the CTAR2 region, the Y384-Y385-D386 pattern is essential for binding the TNF receptor-associated death domain (TRADD) adapter. There is a third region, CTAR3 (aa 232–350), that is not essential for in vitro B cell immortalization and is less well known [67]. In this region located between CTAR1 and CTAR2 (aa 253–302), a variable number of repeat 11 aa elements (4 repeats for B95-8) exist.
Figure 5.
Schematic representation of basic structure of LMP1 protein with the different motifs and their position. TM1–6: transmembrane domains 1–6. The FWLY pattern in TM1 and W98 in TM3 are essential for the association of TM1–2 with TM3–6 and oligomerization signaling. CTAR1–3: carboxyl-terminal activating regions 1–3. PQQAT pattern is necessary for the attachment of TRAF adapters. YYD pattern is essential for binding the TNF receptor-associated death domain (TRADD) adapter.
LMP1 acts principally as a viral pseudoreceptor, which regulates host cell signal transduction by constitutive activation of cell pathways as mitogen-activated protein kinase (MAPK) pathways and principally the extracellular regulated kinases 1 and 2 (ERK1/2), c-Jun amino-terminal kinases 1–3 (JNK1–3), and p38 isoform pathways. LMP1 also induces the phosphatidylinositol 3-kinase (PI3K) pathway, which contributes to survival signals [68] and transcription of activator protein 1 (AP1) [69], PI3K, and AP1 pathways, therefore playing a major role in proliferation and cell cycle control. LMP1 is also responsible for the activation of JAK/STAT and interferon regulatory factor 7 (IRF7) pathways and for aberrant constitutive NF-kB activation. Indeed, the CTAR1 PXQXT pattern is able to engage TRAFs, leading finally to the activation of noncanonical NF-kB pathway that controls processing of the NF-kB2/p100 precursor [70]. The CTAR2 YYD pattern is in turn implicated in the activation of the canonical NF-kB pathway [71] after binding of tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)-associated via TRADD and receptor-inter-acting protein 1 (RIP1). A wider region of LMP1 seems to be responsible for binding RIP1 (aa 351–386), compared to TRADD (aa 375–386) [72]. NF-kB is considered to be the principal factor by which LMP1 regulates gene expression and modifies cell behavior [73]. Activation of NF-kB is associated with upregulation of anti-apoptotic genes [32, 74] and downregulation of pro-apoptotic factors, as well as induction of tumorigenesis-associated B-cell activation markers [75, 76]. CTAR3, less well defined, seems to activate SUMOylation pathways and participate in the maintenance of EBV latency and control of cell migration, a hallmark of oncogenesis [77, 78].
Besides its ability to transform B cells, during the latency state, LMP1 seems also to be able to facilitate the release of virions from B cells during lytic replication [32].
Variations in the LMP1 sequence have been widely studied, particularly in the context of its impact on clinical occurrence or evolution. A 30 bp deletion (del30), resulting in a 10 aa loss in the C-terminal (aa 343–352), was first described in the Cao cell isolate from a Chinese NPC [79]. In addition, this isolate harbored numerous substitutions. A high prevalence of the same deletion, as reviewed by Chang et al. [8], was found in Asian NPC biopsy tissues [80, 81], in lymphomas and EBV-related gastric cancers from Eastern Asia [82] and in Asian nasal NK/T-cell lymphomas [83, 84]. Del30 was shown to be often associated with the G335D mutation in NPC, and such strains were reported to have a greater transforming activity in vitro than the reference LMP1 [85, 86]. If the 30 bp deletion is partly localized to CTAR2, it does not alter NF-kB activation [87] and finally does not modify signaling properties [88]. However, it is clear that strains bearing del30 are selected over the wt-LMP1 variants in NK/T-cell lymphomas [83] and NPC tumors [89]. Given that del30 strains have been currently detected in normal carriers [90] or in various EBV-associated diseases [91], and, because of a low prevalence of del30 strains in samples from Africa, North America, and Europe [8, 92], it is generally admitted that LMP1 del30 may represent a geographic polymorphism rather than a disease-associated polymorphism [93]. In a study, we carried out in France in patients with NK/T lymphoma, we found a del30 EBV in 4/4 biopsies studied and in 46.1% of total blood samples analyzed, while in a control population, the deletion was present in 4.8% of cases [94]. Other deletions were also described, such as the rare C terminal 69 bp deletion reported to weakly activate the AP1 transcription factor [95], or the 15 bp deletion (aa 275–279) frequently encountered in Western Europe [94].
Otherwise, numerous substitutions have been described in LMP1 (Table 3), particularly in the N-terminal extremity. Some authors have made attempts to classify viral strains by taking into account these substitutions with the aim of highlighting a viral implication in certain pathologies [99]. Thus, Mainou and Raab-Traub [88] classified EBV into seven variants, namely Alaskan, China 1, China 2, Med+, Med-, NC, and B95-8, all having the same in vitro transforming potential and signaling properties. Zuercher et al. [98] mentioned two polymorphisms, I124V/I152L and F144I/D150A/L151I, which seem to be markers of increased NF-kB activation in vitro. Lei et al. [96] distinguished four models according to the substitutions occurring in both the LMP1 gene and its promoter. The patients suffering from NPC that they studied all carried a strain belonging to pattern B, while the BLs were distributed among the four patterns. Many authors recognize two evolutionarily distinct clusters, Asian-derived EBV strains including GD2, HKNPC1, and Akata strains and non-Asian and African/American strains including AG876, B95-8, and Mutu strains, suggesting that the LMP1 gene could be used as a geographic marker [25, 97].
Protein
Role/localization
Main properties
EBNA1
Latency
Initiation of viral episome replication before mitosis
Mitotic segregation of EBV episomes
Transcription of other latency genes (Cp and LMPp enhancer)
Degradation of promyelocytic leukemia protein (PML) bodies
Cellular transcription regulation
EBNA2
Latency
Viral and cellular transcription factor
Initiation and maintenance of B cell immortalization
Blocking of methylation sites for BZLF-1 binding
EBNA-LP
Latency
Coactivator of the transcriptional activator EBNA2
LMP1
Latency
Similarity to constitutively activated CD40
Constitutive activation of cell pathways
Maintenance of EBV latency and control of cell migration
BNRF1
Tegument
Establishment of latency and cell immortalization
Increase in the number of cellular centrioles
BPLF1
Tegument
Downregulation of viral ribonucleotide reductase (RR)
Disruption of damaged DNA repair
Decreasing of innate immunity
BKRF3
Tegument
DNA replication and repair—viral DNA mutagenesis prevention
Table 2.
Main properties of proteins developed in this chapter.
Finally, it should be noted that LMP1 carries a molecular signature of accelerated evolution rate probably due to positive selection as deduced from a significant proportion of nonsignificant variations [26].
So, regarding LMP1, which is the most oncogenic latency protein, two geographic clusters appear to exist corresponding to an Asian variant and a non-Asiatic variant. The described 30 bp deletion is mainly present on Asian strains, and it shows an obvious tropism for nasopharynx. Although many substitutions have been described, little work is done to analyze changes in LMP1 properties based on these substitutions. NPC could be associated with a particular strain, but this remains to be confirmed.
5. Variability of tegument proteins
After the latency proteins, the tegument proteins carry the most changes, and among them, the most mutated are BNRF1, BPLF1, and BKRF3, which will be detailed, as well as BBRF2. This latter protein appears to play an important role in viral infectivity [100], but its structure and function are poorly known today. For this reason, BBRF2 will not be developed here.
5.1 BNRF1
EBV major tegument protein BNRF1 contains 1318 aa, and its structure is shown schematically in Figure 6. BNRF1 is a member of a protein family with homology to the cellular purine biosynthesis enzyme FGARAT. BNRF1 is involved in the establishment of latency and cell immortalization by hijacking the antiviral DAXX (death domain-associated protein-6) histone chaperone [101]. BNRF1 seems to have lost conventional purine biosynthesis activity. It forms a stable quaternary complex with DAXX histone-binding domain (HBD), H3.3 and H4 [102], responsible for BNRF1 localization to PML nuclear bodies involved in antiviral intrinsic resistance and transcriptional repression of host cells. In the presence of BNFR1, DAXX can no longer collaborate with ATRX to assemble histone variant H3.3 into repressive chromatin at GC-rich repetitive DNA. Binding to DAXX, histone H3.3 and histone H4 occur, respectively, via the BNRF1 DAXX interaction domain (DID) (aa 360–600) and BNRF1 residues 40–52 and 99–102. Huang et al. [102] demonstrated that the quaternary complex formation is abrogated when dual mutations V546D/L548D and D568A/D569A occurred on BRNF1 DID and is partially diminished in vitro in case of dual mutations Y390A/K461A and V546S/L548S on BNRF1 DID. BNRF1 mutations at K461A, Y390A/K461A, V546S/L548S or Y390A, V546A/L548A, and D568A/569A moderately or severely reduced BNRF1 colocalization at PML nuclear bodies, respectively. A PurM-like domain (610–976) and a GATase domain (1037–1318) were defined. It has also recently been shown that BNRF1 can cause an abnormal increase in the number of cellular centrioles [103]. This phenomenon can lead to aneuploidy or structural chromosome abnormalities and, possibly, to carcinogenesis. The gene regions concerned have not been described.
Figure 6.
Schematic representation of basic structure of BNRF1 protein with the different motifs and their position. H3.3 and H4 regions, respectively, involved in binding to H3.3 and H4. DID: DAXX-interaction domain, domain implicated in binding to DAXX (death-domain associated protein-6) histone chaperone. PurM-like domain and GATase domain were noted, as well as the different mutations discussed.
BNRF1 is reported to be one of the most frequently mutated tegument proteins. It is interesting to note that a nonsense mutation was described in C666–1, an EBV-positive NPC cell line, with no major structural alterations in the BNRF1-deleted virus [92].
So, the mutations described for BNRF1 do not appear to correspond to a particular geographical distribution. On the other hand, some mutations seem to be able to modify DNA chromatinization, thus affecting the transcription, and therefore have important consequences on cell functioning.
5.2 BPLF1
BPLF1, the largest EBV protein (3149 aa), is a late lytic tegument protein. BPLF1 possesses a deubiquitinating (DUB) activity. BPLF1 is able to downregulate viral ribonucleotide reductase (RR) activity, by deubiquitination of the large subunit RR1 [104], and to specifically deubiquitinate proliferating cell nuclear antigen (PCNA), a DNA polymerase processivity factor, thus disrupting the repair of damaged DNA [105]. By triggering activation of repair pathways and co-opting DNA repair and replication factors, the virus could create genomic instability. The DUB activity is carried by the first 246 aa of the N-terminal region, and the C61 residue of the catalytic triad (Cys-His-Asp) is essential for activity [104]. BPLF1 relocalizes Pol 𝜼 to nuclear sites of viral DNA production, thereby bypassing DNA damage [106]. This mechanism contributes to efficient production of infectious virus.
BPLF1 is also able to deubiquinate cell factors, such as TRAF6, NEMO, and IkBα, leading to TLR signaling inhibition through both MyD88- and TRIF-dependent pathways, thus decreasing innate immune responses by reduced NF-kB activation and proinflammatory cytokine production [107]. It is noteworthy that the same catalytic active site also carries a deneddylating activity shown to target cullin ring ligases, potentially affecting viral replication and infectivity [108]. The role of BPLF1 to help drive human B-cell immortalization and lymphoma formation has also been discussed [109].
Sequencing of various viral strains has shown that BPLF1 is one of the proteins with the greatest number of changes [20, 24, 110]. Most of these mutations are not analyzed in detail, but Kwok et al. [21], working on the sequences of eight NPC biopsy specimens, reported two nonsynonymous mutations in the N-terminal region of the protein that exhibit deubiquitinating activity. The same finding was reported by Simbiri et al. [110], who also described 3 C-terminal mutations (L2935P, P2987L, and R3005Q). A single-nucleotide deletion coupled with a single-nucleotide insertion three nucleotides away was reported by Zeng et al. [13] in a NPC strain. As a result, two aa substitutions (GA/EG) were predicted to occur. Tu et al. [24] undertook phylogenetic analysis based on several reported EBV genome sequences and some major genes as BPLF1. They observed that EBV Asian subtypes clustered as a separate branch from the non-Asian ones.
So, as with other proteins, it seems that the Asian strains carry a protein different from the other strains. Substitutions occurring in the region carrying the deubiquitinase activity could have biological consequences.
5.3 BKRF3
BKRF3 is a small protein (255 aa), which belongs to the early lytic gene family, and encodes an uracil-DNA glycosylase (UDG), which removes inappropriate uracil residues from DNA. BKRF3 excises uracil bases incorporated in double-stranded DNA due to uracil misincorporation or more often cytosine deamination [111, 112]. BKRF3 participates in DNA replication and repair and prevents viral DNA mutagenesis. BKRF3 shares substantial similarity in overall structure with the one UDG family. Four of the five catalytic motifs are completely conserved (aa 90–94, 110–114, 146–149, 191–192), whereas the fifth domain (aa 213–229) carries a seven-residue insertion in the leucine loop [113]. In addition, the 29 N-terminal aa carry a nuclear localization signal (sequence KRKQ). Only changes in BKRF3 that do not severely affect viral replication can be retained, but it may be considered that these mutations cause a change in virus-cell interrelations.
6. Conclusion
The aim of this chapter was to take stock of the most frequently observed variations in the EBV genome and more particularly to see if some of these variations are considered to be involved in tumor pathology. The candidate viral genes concerned are numerous; those developed here are the most affected, and the mutations reported in the literature have been identified. Some mutations have been well studied, in particular as regards their impact on the structure or functionality of the protein or the cellular consequences of these modifications. However, most mutations have only been described. If a tumorigenic impact of viral mutations is not yet certain, many authors agree that geographic variants exist, and it seems clear that Asian strains have different characteristics from non-Asian strains. Further work is necessary to complete the mass of information and analysis, not at the level of one or several genes, but at the level of the entire genome.
\n',keywords:"Epstein-Barr virus, lymphoma, carcinoma, mutation, sequence, next generation sequencing",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73024.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73024.xml",downloadPdfUrl:"/chapter/pdf-download/73024",previewPdfUrl:"/chapter/pdf-preview/73024",totalDownloads:398,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 1st 2020",dateReviewed:"June 16th 2020",datePrePublished:"August 19th 2020",datePublished:"December 22nd 2021",dateFinished:"August 19th 2020",readingETA:"0",abstract:"The Epstein-Barr virus (EBV) is a DNA virus with a relatively stable genome. Indeed, genomic variability is reported to be around 0.002%. However, some regions are more variable such as those carrying latency genes and specially EBNA1, -2, -LP, and LMP1. Tegument genes, particularly BNRF1, BPLF1, and BKRF3, are also quite mutated. For a long time, it has been considered for this ubiquitous virus, which infects a very large part of the population, that particular strains could be the cause of certain diseases. However, the mutations found, in some cases, are more geographically restricted rather than associated with proliferation. In other cases, they appear to be involved in oncogenesis. The objective of this chapter is to provide an update on changes in viral genome sequences in malignancies associated with EBV. We focused on describing the structure and function of the proteins corresponding to the genes mentioned above in order to understand how certain mutations of these proteins could increase the tumorigenic character of this virus. Mutations described in the literature for these proteins were identified by reporting viral and/or cellular functional changes as they were described.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73024",risUrl:"/chapter/ris/73024",signatures:"Sylvie Ranger-Rogez",book:{id:"9619",type:"book",title:"Epstein-Barr Virus",subtitle:"New Trends",fullTitle:"Epstein-Barr Virus - New Trends",slug:"epstein-barr-virus-new-trends",publishedDate:"December 22nd 2021",bookSignature:"Emmanuel Drouet",coverURL:"https://cdn.intechopen.com/books/images_new/9619.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-490-6",printIsbn:"978-1-83968-489-0",pdfIsbn:"978-1-83968-491-3",isAvailableForWebshopOrdering:!0,editors:[{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"317161",title:"Prof.",name:"Sylvie",middleName:null,surname:"Ranger-Rogez",fullName:"Sylvie Ranger-Rogez",slug:"sylvie-ranger-rogez",email:"sylvie.rogez@unilim.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Evolving knowledge of the EBV genome",level:"1"},{id:"sec_3",title:"3. The most variable regions of the genome",level:"1"},{id:"sec_4",title:"4. Variability of main latency proteins",level:"1"},{id:"sec_4_2",title:"4.1 EBNA1",level:"2"},{id:"sec_5_2",title:"4.2 EBNA2",level:"2"},{id:"sec_6_2",title:"4.3 EBNA-LP (EBNA-leader protein)",level:"2"},{id:"sec_7_2",title:"4.4 LMP1",level:"2"},{id:"sec_9",title:"5. Variability of tegument proteins",level:"1"},{id:"sec_9_2",title:"5.1 BNRF1",level:"2"},{id:"sec_10_2",title:"5.2 BPLF1",level:"2"},{id:"sec_11_2",title:"5.3 BKRF3",level:"2"},{id:"sec_13",title:"6. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from BURKITT’S lymphoma. Lancet. 1964;1:702-703. DOI: 10.1016/s0140-6736(64)91524-7'},{id:"B2",body:'Zur Hausen H, Schulte-Holthausen H. 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Department of Virology, University Hospital Dupuytren, France
Faculty of Pharmacy, UMR CNRS 7276, UMR INSERM 1262, France
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The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
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The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence"},{id:"23",title:"Computational Neuroscience",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. This topic is dedicated to biologically plausible descriptions and computational models - at various abstraction levels - of neurons and neural systems. 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Novel computational algorithms for image analysis, scene understanding, biometrics, deep learning and their software or hardware implementations for natural and medical images, robotics, VR/AR, applications are some research directions relevant to this topic.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR"},{id:"25",title:"Evolutionary Computation",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization"},{id:"26",title:"Machine Learning and Data Mining",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence"},{id:"27",title:"Multi-Agent Systems",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. 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We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Artificial Intelligence",id:"14"},selectedSubseries:null},seriesLanding:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems. \r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
",coverUrl:"https://cdn.intechopen.com/series/covers/25.jpg",latestPublicationDate:"April 13th, 2022",hasOnlineFirst:!1,numberOfOpenTopics:4,numberOfPublishedChapters:9,numberOfPublishedBooks:1,editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. Dr. Summers holds a BA in Zoology and Psychology, an MA in Ecology, and Ph.D. in Systems Ecology/Biology.",institutionString:null,institution:{name:"Environmental Protection Agency",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"38",title:"Pollution",keywords:"Human activity, Pollutants, Reduced risks, Population growth, Waste disposal, Remediation, Clean environment",scope:"
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",annualVolume:11966,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},{id:"39",title:"Environmental Resilience and Management",keywords:"Anthropic effects, Overexploitation, Biodiversity loss, Degradation, Inadequate Management, SDGs adequate practices",scope:"
\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"
\r\n\tIn general, the harsher the environmental conditions in an ecosystem, the lower the biodiversity. Changes in the environment caused by human activity accelerate the impoverishment of biodiversity.
\r\n
\r\n\tBiodiversity refers to “the variability of living organisms from any source, including terrestrial, marine and other aquatic ecosystems and the ecological complexes of which they are part; it includes diversity within each species, between species, and that of ecosystems”.
\r\n
\r\n\tBiodiversity provides food security and constitutes a gene pool for biotechnology, especially in the field of agriculture and medicine, and promotes the development of ecotourism.
\r\n
\r\n\tCurrently, biologists admit that we are witnessing the first phases of the seventh mass extinction caused by human intervention. It is estimated that the current rate of extinction is between a hundred and a thousand times faster than it was when man first appeared. The disappearance of species is caused not only by an accelerated rate of extinction, but also by a decrease in the rate of emergence of new species as human activities degrade the natural environment. The conservation of biological diversity is "a common concern of humanity" and an integral part of the development process. Its objectives are “the conservation of biological diversity, the sustainable use of its components, and the fair and equitable sharing of the benefits resulting from the use of genetic resources”.
\r\n
\r\n\tThe following are the main causes of biodiversity loss:
\r\n
\r\n\t• The destruction of natural habitats to expand urban and agricultural areas and to obtain timber, minerals and other natural resources.
\r\n
\r\n\t• The introduction of alien species into a habitat, whether intentionally or unintentionally which has an impact on the fauna and flora of the area, and as a result, they are reduced or become extinct.
\r\n
\r\n\t• Pollution from industrial and agricultural products, which devastate the fauna and flora, especially those in fresh water.
\r\n
\r\n\t• Global warming, which is seen as a threat to biological diversity, and will become increasingly important in the future.
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\r\n\tWater is not only a crucial substance needed for biological life on Earth, but it is also a basic requirement for the existence and development of the human society. Owing to the importance of water to life on Earth, early researchers conducted numerous studies and analyses on the liquid form of water from the perspectives of chemistry, physics, earth science, and biology, and concluded that Earth is a "water polo". Water covers approximately 71% of Earth's surface. However, 97.2% of this water is seawater, 21.5% is icebergs and glaciers, and only 0.65% is freshwater that can be used directly by humans. As a result, the amount of water reserves available for human consumption is limited. The development, utilization, and protection of freshwater resources has become the focus of water science research for the continued improvement of human livelihoods and society.
\r\n
\r\n\tWater exists as solid, liquid, and gas within Earth’s atmosphere, lithosphere, and biosphere. Liquid water is used for a variety of purposes besides drinking, including power generation, ecology, landscaping, and shipping. Because water is involved in various environmental hydrological processes as well as numerous aspects of the economy and human society, the study of various phenomena in the hydrosphere, the laws governing their occurrence and development, the relationship between the hydrosphere and other spheres of Earth, and the relationship between water and social development, are all part of water science. Knowledge systems for water science are improving continuously. Water science has become a specialized field concerned with the identification of its physical, chemical, and biological properties. In addition, it reveals the laws of water distribution, movement, and circulation, and proposes methods and tools for water development, utilization, planning, management, and protection. Currently, the field of water science covers research related to topics such as hydrology, water resources and water environment. It also includes research on water related issues such as safety, engineering, economy, law, culture, information, and education.
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