The detailed measurements of the CSA, when εr = 4.0 and thickness t = 1.6 mm of the dielectric substrate.
\r\n\tThe main cause of failure in TKA remains malaignment so preoperative planning and understanding of the principles are crucial in TKA.
\r\n\tThe aim of this book is to discuss preoperative planning, surgical principles, strategies and particular situations in total knee arthroplasty. This book is intended to contribute to the achievement of better results and functional scores in TKA.
The popularity of circularly polarized (CP) antennas is increasing because the use of CP waves is thought of as a good way to eliminate the null angle of radiofrequency (RF) transmission signals. In particular, the necessity of small and simple CP antennas is increasing by the year as mobile communication devices are being equipped with radiofrequency identifier (RFID) systems and global navigation satellite systems (GNSSs). The recent technological evolution, such as wireless power transmission and wireless links between electric appliances, equips us with the motivation to develop compact and high-performance CP antennas.
\nThe turnstile antenna invented by Brown, which is recently called the crossed dipole.
The crossed dipole being spaced by a quarter wavelength instead of using a phase shifter.
The crossed-dipole antenna is the most well-known circularly polarized antenna, which was invented in 1936 by Brown [1–3] as “the turnstile antenna.” Brown’s idea is that two half wavelength dipoles crossed and fed with 90° phase differences, as shown in Figure 1, are the simplest way to make good circularly polarized (CP) waves. Recently, we call this turnstile antenna as the “crossed dipole.” In addition, being spaced by a quarter wavelength as shown in Figure 2, the crossed-dipole antenna no longer needs to be fed with a 90° phase-shifting circuit. Although the crossed-dipole antenna has become a basic structure of many CP antennas, its beamwidths of CP waves are generally narrow.
\nRadiating CP waves with wide beamwidths is also a necessary requirement for CP antennas. The Lindenblad antenna [4] is famous as an omnidirectional CP antenna, which is constituted by radially placing two or more sets of crossed dipoles tilted slightly from the transmitting direction, as shown in Figures 3 and 4, for omnidirectional CP radiation. In addition, constituted by folded antennas instead of dipoles [5], as shown in Figure 5, the Lindenblad antenna radiates with higher gain because its impedance becomes higher. Although the crossed-dipole antenna and the Lindenblad antenna are basic arrangements of CP antennas, it is difficult to make them so compact that they can be installed inside mobile communication devices.
An outline structure of the Lindenblad antenna.
The side view of the Lindenblad antenna shown in Figure 3.
The crossed dipoles or the Lindenblad antenna which is constituted by folded antennas instead of dipoles.
Microstrip patch antennas are a good structure to make thin antennas. Many structures of microstrip patch antennas radiating CP waves were proposed [6]. However, their impedance bandwidths and beamwidths are narrow. Moreover, they need wide enough ground planes. For these reasons, microstrip patch antennas are not suitable for making a printable planar antenna on a one-layer film, which is considered a desirable structure as a built-in antenna for mobile communication devices. Therefore, a new idea for antenna structures is needed for making a compact printable omnidirectional CP antenna.
\nBased on the previous discussions, the author chose loop antennas as a basic structure for developing a new CP antenna because loop antennas are generally thought of as being thin and capable of being miniaturized easily, having wide impedance bandwidths, wide beamwidths, and high impedance. First, a loop antenna was arranged like a cross shape for radiating CP waves. Second, the cross-shaped loop antenna (CSA) was fed by a dipole antenna for achieving wide beamwidths, multipolarization, and stable feedings. In the next section, the development procedure and principle of these new antennas are explained.
\nThe basic structure of the CP antenna invented by the author is introduced. As mentioned before, the author invented a CP antenna based on loop antennas [7]. The antenna is constituted by a loop antenna arranged like a cross shape; therefore, the antenna is called the “cross-shaped loop antenna (CSA)”. Its outline structure is shown in Figure 6. The principle of this CSA is based on the crossed-dipole antenna. This means that the antenna is constituted by two crossed elements being fed with a 90° phase difference. Although making a cross-shaped element is easy, feeding it with different phases is a difficult problem.
\nFirst, let us think about CSA’s structure. As already mentioned, CSA is constituted by arranging a single-turned loop like the cross shape. This means that CSA is completed by turning an electric wire along the outer side of the cross. As a result, CSA is formed by a horizontal element and a vertical element like the crossed-dipole antenna. There are two main differences between CSA and the crossed-dipole antenna: (1) folded antennas are used instead of dipole antennas and (2) CSA is made by connecting folded antennas in series, while the crossed-dipole is made by connecting dipole antennas in parallel.
\nThe outline structure of CSA.
Second, let us think about the feeding port of the CSA. To make a compact printable antenna, the horizontal element needs to share its port and plane with the vertical element. The author thought that Bolster’s idea [8] would solve this problem. Bolster said that a crossed-dipole antenna can be constituted on the same plane that shares the same port, if the admittance of the horizontal element and that of the vertical element is set to the same conductance, and the arguments have a 90° difference. From this, the author had the idea that CSA could be considered because two-folded antennas are connected in a series as sharing one feeding port, if the feeding port was put in the joint between the upper element and the right element. Figure 7 shows the equivalent circuit of CSA.
The equivalent circuit of CSA.
According to Bolster’s idea, CSA will radiate good CP waves, if the impedances of the horizontal element and vertical element are set as to be close and the arguments are set to a 180° difference. Then, the length of the horizontal folded antenna and that of vertical folded antenna are chosen by Figure 8, which shows moduli and arguments of a folded antenna’s impedance with various lengths L. For example, the horizontal length should be Lx marked in Figure 8, if the vertical length is chosen as Ly. Their impedance moduli |Zx| and |Zy| are close, and impedance arguments arg|Zx| and arg|Zy| are in almost 180° difference.
Moduli and arguments of a folded antenna’s impedance with various lengths L.
Note that the wavelength λ is defined as the following equation (1):
\nf is a frequency, c is the light velocity, and εr is a relative permittivity of a dielectric substrate on which antennas are constituted. The results in Figure 8 were calculated when the thickness and relative permittivity of the dielectric substrate were defined as 1.6 mm and 4, respectively. All simulation results shown in the chapter are calculated by Sonnet 16.52.
\nThe characteristics of CSA whose measurements are set based on this procedure are as follows: Figure 9(a) shows S11 characteristics and Figure 9(b) shows radiation patterns. Note that the detailed measurements of CSA are shown in Table 1, and λ is the wavelength of the center frequency f0. CSA radiates right-handed CP waves around the frequencies in which S11 is lower than −10 dB.
\nThe detailed measurements of the CSA, when εr = 4.0 and thickness t = 1.6 mm of the dielectric substrate.
Characteristics of CSA whose measurements are set as shown in Table 1: (a) S11 characteristics, and (b) radiation patterns at f = f0 and φ = 0°.
Two optional structures of CSA.
In fact, there are some more possible combinations of the horizontal length and vertical length. Figure 10 shows two additional combinations of those lengths, and Figure 11 shows characteristics of these CSAs. This means that you can choose the CSA from two optional structures depending on the space: a rectangle or a square space, assigned to the CSA. Moreover, if the horizontal length is shorter than the vertical length, the CSA will radiate right-hand CP (RHCP) waves. On the other hand, if the horizontal length is longer than the vertical length, CSA will radiate left-hand CP (LHCP) waves.
Characteristics of the two optional structures of CSA as shown in Figure 10: (a) S11 characteristics, and (b) radiation patterns at f = f0 and φ = 0°.
Let us arrange the CSA prototype using a printed circuit board (PCB). Wavelengths shorten when the CSA is formed on a PCB and the feeding port cannot be put at the symmetrical center of the CSA. For these reasons, the prototype CSA has to be tuned in the exact frequency by adjusting its measurements. As a result, you get the final structure of a CSA as shown in Figure 12 and Table 2. Note that PCB is used whose εr is 4.4, tanδ is 0.016, and thickness is 1.6 mm. S11 characteristics and radiation patterns of this CSA prototype are shown in Figure 13(a) and (b), respectively. In Figure 13(a) and (b), simulation results are compared with measurement results.
The detailed measurements of the CSA prototype when the dielectric substrate is used whose εr is 4.4, tanδ is 0.016, and thickness is 1.6 mm.
These results show that CSA radiates CP waves at f0 in which S11 reached −10 dB: the 3-dB axial ratio beamwidth is 100° and the 10-dB impedance bandwidth is 3%. There are some differences between the simulation and measurement results. These differences occur because the simulation results are calculated by feeding CSA through an ideal balanced port. On the other hand, measurement data are obtained by feeding CSA through a coaxial cable. These results show that the balance of the feeding port is important for CSA. Therefore, CSA is a simple CP antenna for application using balanced ports such as RFID tags.
\nThe structure of the CSA prototype.
Characteristics of the CSA prototype as shown in Figure. 12: (a) S11 characteristics, and ( b) radiation patterns at f = f0 and φ = 0°.
As a matter of fact, there are many applications in which coaxial cables are thought of as a useful feeding way. However, CSA needs to be fed through balanced ports. Measurement data in Figure 13(b) show that CSA no longer radiates CP waves, if it is fed through a coaxial cable without any treatments. In the next section, the feeding mechanism, which makes it possible to feed CSA through a coaxial cable, will be suggested. The feeding mechanism should be simple but helps CSA to radiate CP waves even if it is fed through a coaxial cable.
\nA simple way to feed CSA through a coaxial cable is discussed in this section. As mentioned before, the balance of the port is extremely important for CSA. For this reason, baluns, balanced-unbalanced transformers, are needed in general to feed CSA through a coaxial cable. However, baluns tend to need wider spaces than antennas. If the size of a balun becomes the same size as CSA, the usefulness of CSA’s simple structure will be lost. Therefore, the feeding mechanism, which is as simple as possible, can be incorporated into CSA as its elements should be invented.
\nThe structure of DFCSA.
Feeding loop antenna indirectly by using monopole elements suggested by Nakano is famous [9]. This is a feeding mechanism where a monopole element connected to a coaxial cable is put close to a loop antenna. Although this method could be used for CSA, it would need thick substrates and a ground plane. To keep CSA as a thin structure, the author tries to feed CSA by using a dipole antenna. The author also thought that a dipole antenna will work not only as a feeder but also as a radiator, if used for CSA.
\nIn fact, putting a dipole antenna close to a loop antenna is difficult because they interfere with each other. This means that they no longer behave as they should. To solve this problem, gaps are made in CSA. Figure 14 shows a representative structure of CSA fed with a dipole feeder. This antenna is named the dipole-fed cross-shaped spiral antenna (DFCSA). A dipole feeder is located in the center of CSA. The dipole feeder has a feeding port. CSA is turned around the dipole feeder in a cross shape. CSA does not have any feeding ports.
\nNext, two gaps are made at the CSA’s joint between the upper element and the right element and between the lower element and the left element to avoid interference between the dipole antenna and CSA. S11 characteristics of DFCSA are shown in Figure 15 when its measurements are set as shown in Table 3. S11 characteristics show that DFCSA has three resonant frequencies. Radiation patterns of each resonant frequency are shown in Figure 16. These results show that DFCSA radiates linear polarized (LP) waves at the lowest and highest frequencies and radiates CP waves at the middle frequency.
\nS11 characteristics of DFCSA.
Lx | \nLy | \nLd | \nsx (mm) | \nsy (mm) | \nw (mm) | \ns4 (mm) | \nL4 (mm) | \n
---|---|---|---|---|---|---|---|
0.668 λ | \n0.657λ | \n0.577λ | \n3.0 | \n2.0 | \n1.0 | \n0.3 | \n5.0 | \n
The detailed measurements of the DFCSA when εr = 4.4, tanδ = 0.016, and thickness t = 1.6 mm of the dielectric substrate.
Radiation patterns at three resonant frequencies.
To validate the effectiveness of the dipole feeder, the measurement results are compared with the simulation results in Figures 15 and 16. In S11 results, there are some differences around the highest resonant frequency. This is because the dipole feeder works as a radiator around this frequency. Measurement radiation patterns show that DFCSA radiates CP waves at the middle resonant frequency and LP waves at the lowest and highest frequencies. For these reasons, the dipole feeder works well not only as a feeder for a coaxial cable but also as a radiator for LP waves.
\nTo conclude, the mechanism of the dipole feeder is discussed. According to the structure of DFCSA, the dipole feeder seems to work like a microstrip balun constituted by the quarter-wavelength coupler of a dipole and CSA [10]. However, the reason why a dipole feeder helps feed CSA through a coaxial cable is simpler [11]. The measurement data in Figure 16 show that radiation patterns of RHCP waves tilt by a few degrees. This is because CSA’s right element is fed indirectly through the dipole’s right element, which is connected to the outer conductor of the coaxial cable. In the same manner, CSA’s left element is fed indirectly through the dipole’s left element, which is connected to the center line of the coaxial cable. Although the current amplitude of the dipole’s right element is different from that of the dipole’s left element, there is no difference between the current phase of the right’s dipole and that of the left’s dipole. For this reason, the radiation directivity rotates some angles toward the direction of the right dipole element. This rotation angle is about 5°. The dipole feeder helps to reduce the effect of an unbalanced feed.
\nThe simple CP antenna (CSA) and its principle were introduced. The fact that CSA was a printable antenna, which can be constituted on a single side of a circuit board without ground plane, was shown. When CSA was applied to antenna systems using balanced ports, it radiated good CP waves; the 3-dB axial ratio bandwidth was 1.5%, the 3-dB beamwidth was 100°, and the 10-dB impedance bandwidth was 3%. The maximum radiation gain and efficiency at the center frequency were, respectively, 0.96 dBi and 85% when the size of the antenna was about the square of the quarter wavelength.
\nAn applied structure of CSA, which can be fed through a coaxial cable, was presented. The applied CSA was achieved by incorporating the dipole feeder into CSA. For this reason, the antenna was named the dipole-fed CSA (DFCSA). DFCSA radiated good CP waves without deterioration of S11 characteristics, even when it was fed through a coaxial cable. The merit of using the dipole feeder was that CSA developed into a multipolarization antenna. DFCSA had three resonant frequencies in S11 characteristics and radiated CP waves at one of them and LP waves at the others. The detailed characteristics of DFCSA are shown in Table 4.
Frequency f/f0 | \n1 | \n0.7 | \n1.146 | \n|
Polarization | \nCP | \nLP | \nLP | \n|
Gain | \n−3 dBi | \n0 dBi | \n1.7 dBi | \n|
Efficiency | \n48% | \n76% | \n87% | \n|
Bandwidth | \nAxial ratio <3 dB | \n0.6% | \n– | \n– | \n
S11 < −10 dB | \n1.3% | \n2% | \n12% | \n|
Beamwidth | \n95° | \nOmnidirectional | \n100° | \n
Characteristics of DFCSA.
To my knowledge, CSA is the simplest CP antenna. It has multiple advantages: (1) it can be fed through not only balanced ports but also unbalanced ports, (2) it can radiate CP waves with a wide beamwidth, and (3) it can be developed into multiband and multipolarization antennas. It also has the large possibility of being flexibly modified to any structures and to be made electrically small in structure in future studies. The representative structures of CSA and DF-CSA are only some examples, which have not been miniaturized yet. They can be miniaturized by using shortening methods of dipole elements. Miniaturized structures, which can be called as electrically small ones, are going to be suggested in the author’s next publications.
\nThis work was supported by JSPS KAKENHI Grant Numbers 26420359 and 15H02135. The author would like to thank the Research Institute for Sustainable Humanosphere of Kyoto University.
\nMyasthenia Gravis (MG) is an autoimmune disease that afflicts a significant human population. MG patients suffer from a variable degree of skeletal muscle weakness. The symptoms range from mere lack of muscle strength to life-threatening respiratory failure. MG is a chronic disease that can last many years and negatively impact the quality of living and life expectancy of afflicted individuals. Although MG rate is reported to be 7–20 out 100,000 [1] and the diagnosed MG cases are increasing, probably due to increased awareness of this debilitating disease, the aging population and other intrinsic and extrinsic factors that disturb the human immune system [1].
The majority of MG cases (~85%) are caused by pathological autoantibodies to muscle nicotinic acetylcholine receptors (nAChRs), a ligand-gated ion channel that mediates rapid signal communication between spinal motor neurons and the muscle cells. Autoantibodies against other neuromuscular junction (NMJ) proteins, including muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4), can also cause muscle weakness in a small fraction of patient [2, 3]. The heterogeneous nature of MG autoantibody presents a challenge to both diagnosis and treatment of the disease.
Current treatment regimens for MG include anticholinesterase inhibitors, thymectomy, immunosuppressants, plasmapheresis, or intravenous immunoglobulins [4]. Most MG patients respond favorably to these treatment options to achieve effective symptom relief, and in some cases even clinical remission. Cholinesterase inhibiting drugs can temporarily enhance neuromuscular transmission by delaying the breakdown of acetylcholine (ACh) to compensate for the loss of NMJ nAChRs, but this treatment option only works in a fraction of patients and does not alter the autoimmune response. The more broadly used nonspecific immunosuppressive drugs work by inhibiting lymphocyte activation and proliferation but have little effect on long-lived plasma cells that are terminally differentiated and continue producing pathogenic antibodies [5, 6]. This may explain why treatment with non-specific immunosuppressive drugs takes long time to show clinical improvement.
There are two major limitations in the current MG treatment. First, up to 10% of MG patients do not tolerate or are resistant to the available treatments [7]. Second, all immunosuppressant drugs, which are often used in the long-term control of chronic MG, inevitably carry the serious risks of infection and cancer. As such continued efforts have been put into searching for better MG treatment, as evident by the long list of clinical trials (
An ideal therapeutic approach to MG would be to inhibit the pathogenic autoimmune response to nAChR specifically without disrupting other functions of the immune system. Because nAChR is a dominant autoantigen in MG, it has served as the primary target for a wide range of studies attempting to develop antigen-specific therapy to induce immune tolerance to nAChR [8, 9, 10, 11, 12, 13, 14]. While some of these approaches showed promising results in animal model of experimental autoimmune MG (EAMG), translation to human MG treatment is uncertain. Furthermore, introducing an autoantigen like nAChR or its derivative peptides risks to inadvertently enhance the pathogenic autoimmune response.
Here, we will first review structural and molecular features of nAChR and its complexes with autoantibodies. Based on insights derived from structural studies, we will discuss several strategies to specifically inhibit the binding of pathological autoantibodies to nAChR or specifically eliminate nAChR-specific B cells.
As the first isolated neurotransmitter receptor and ion channel, nicotinic acetylcholine receptors (nAChRs) have been the focus of extensive studies to understand the basic mechanisms of neuronal signaling. These receptors are also being targeted for drug development against a variety of diseases, including addiction, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, Alzheimer’s disease, pain and inflammation [15]. nAChRs have been analyzed by a variety of biochemical, biophysical and electrophysiological experiments [16]. Tremendous efforts have been put into pursuing the atomic structure of nAChR. Electron microscopic analyses of nAChR from Torpedo marmorata by Unwin and colleagues have led to a 4 Å resolution model of the intact channel [17, 18], providing one of the most comprehensive structural model for nAChR. The structural details, however, are limited by the relatively low resolution. In this regard, the high-resolution structure of the acetylcholine binding protein (AChBP) published by Sixma and colleagues in 2001 was a major breakthrough [19]. AChBP shares ~24% sequence identity with nAChRs and has the same pentameric assembly. Its structures in different bound states have provided detailed information on the binding of a variety of agonists and antagonists [20]. But AChBP does not function as an ion channel and may lack necessary structural features required for transmitting the ligand-binding signal across the protein body [21, 22]. The crystal structures of several prokaryotic homologues of nAChR have also been determined from different species and in different states [23, 24, 25]. These structures together with detailed biochemical and biophysical characterization have provided a great deal of insight into the fundamental mechanisms of ligand-dependent channel gating (reviewed in Corringer et al [26]). More recently, the structure of the anionic glutamate receptor (GluCl) from C. elegans [27], and human α4β2 neuronal nicotinic receptor have also been determined [28]. However, direct structural information of mammalian muscle nAChRs at high resolution will be needed for further dissecting the mechanisms of neuromuscular junction signal transmission and for drug development against MG [29].
Although large quantities of nAChR were available from Torpedo electric ray organ, crystallization was not successful, probably due to the heterogeneity of the protein samples prepared from the natural source. Heterologous expression in bacterial results in insoluble protein is due to the lack of proper post translation modifications such as glycosylation. Yeast Pichia pastoris has been a favorable expression system for overexpressing nAChR because of its mammalian-like glycosylation system. However, the expressed nAChR protein or extracellular domain (ECD) is often unstable, leading to aggregation and low yield [30, 31]. We have employed a number of strategies to overcome this difficulty, including expressing different family members of nAChR or its sub-domain (mostly ECD), constructing AChBP-nAChR chimera, and introducing specific mutations to enhance expression and stability [32]. Using the nAChR α1 as an example, we screened a PCR-generated mutant library of mouse nAChR α1 ECD for variants with increased expression and stability which led to the isolation of a triple mutant (V8E/W149R/V155A) that has much improved expression and stability than the wild type protein, and ultimately the determination of the crystal structure of nAChR α1 ECD bound to a-bungarotoxin at 1.94 Å resolution [22]. Structure comparison with the 4 Å electron microscopic model of nAChR and AChBP reveals that the isolated ECD is very similar to its counterpart in the intact channel and that the stabilizing mutations do not appear to alter the overall structure of the ECD.
All of the three mutations map to the surface of the protein (Figure 1a), with one (V8E) located on the N-terminal helix and the other two (W149R and V155A) located on loop B. The V8E mutation introduces a salt bridge with Lys84 (Figure 1b), whereas the W149R mutation introduces a salt bridge with Asp89 (Figure 1c). These salt bridges apparently contribute to protein stability as evident by the well-defined electron density of these exposed residues with long and charged side chains. Thus, the mutations seem to enhance the protein stability through at least two mechanisms. One is to remove surface exposed hydrophobic residues, including V155A (Figure 1d); the other is to introduce salt bridges on the protein surface. These observations suggest that the ECD of nAChR may be rationally engineered to improve solubility and stability. In principle, one can use homology models to guide the selection of exposed hydrophobic residues and to engineer surface salt bridges, which can increase the stability of recombinant mammalian nAChRs. This insight will be important for the design of stable chimeric nAChR antigen for specific targeting and elimination of nAChR-specific B cells (discussed further below).
Mutations that stabilize nAChR α1 ECD. (a) The three mutations (boxed and indicated by arrow) are mapped on the surface of nAChR α1 ECD (dark green) and away from the binding site of α-bungarotoxin (orange) and the glycan (magenta); (b) the mutation Val8Glu establishes a salt bridge with Lys84. The surrounding structure is well ordered, showing well-defined electron density; (c) the mutation Trp149Arg establishes a salt bridge with Asp89. The side chains of both residues show well-defined electron density; (d) the mutation of Val155Ala removes an exposed hydrophobic residue. The surrounding structure is well ordered (Adapted from Chen [33]).
Most proteins have a densely packed hydrophobic core that is important for stable folding in aqueous solution. However, a hydration pocket was found inside the beta sandwich core of the nAChR α1 ECD [22]. This hydration pocket consists of two buried hydrophilic residues, Thr52 and Ser126, two ordered water molecules, and a few cavities, creating a packing defect near the disulfide that connects the two beta sheets. Both Thr52 and Ser126 are highly conserved in nAChRs but are substituted by large hydrophobic residues (Phe, Leu or Val) in the non-channel homologue AChBPs. This observation suggests that the nAChR ECD has evolved with a non-optimally packed core, hence predisposed to undergo conformational change during ligand-induced gating. Replacing Thr52 and Ser126 with their hydrophobic counterparts in AChBP significantly impaired the gating function of nAChR without affecting the folding of the protein structure [22]. This role of the hydration pocket on the conformation flexibility/dynamics of the nAChR ECD is supported by recent molecular dynamics studies [34]. This model also suggests that the specific location of the hydration cavity is important for a particular class of pentameric LGICs [35]. A practical implication of these observations is that one can design stabilization mutants of LGICs, including nAChR ECD, by structure-guided modifications of such packing defects, which are evolved for intrinsic ion channel functions but may be detrimental to recombinant production of proteins as therapeutic antigen.
Antibodies generated by the immune system may bind various epitopes on nAChR. It is therefore important to know if MG autoantibodies are randomly distributed to various epitopes and if they contribute equally or differently to the disease phenotype. This question is also therapeutically relevant if one wishes to use small molecules or single valent antibody [36] to block the binding of most pathologically relevant autoantibodies to nAChR. Mammalian muscle nAChR has a pentameric structure composed of two α1, one β1, one δ, and one ε (adult form) or γ (fetal form) subunit(s) [18]. Extensive studies suggest that autoantibodies to α1 play a major role in MG pathology [37, 38, 39, 40]. Furthermore, more than half of all autoantibodies in MG and EAMG bind an overlapping region on the nAChR α1 subunit, known as the main immunogenic region (MIR) [41]. The MIR is defined by the ability of a single rat monoclonal antibody (mAb), mAb35, to inhibit the binding of about 65% autoantibodies from MG patients or rats with EAMG [42, 43, 44]. Subsequent studies have mapped MIR to a peptide region that spans residues 67–76 on nAChR α1 [45, 46]. Monoclonal antibodies directed to the MIR can passively transfer EAMG and possess all the key pathological functions of serum autoantibodies from MG patients [37]. Moreover, a recent study showed that titer levels of MIR-competing autoantibodies from MG patients, rather than the total amount of nAChR autoantibodies, correlate with disease severity [47]. These observations suggest that autoantibodies directed to the MIR on nAChR α1 play a major role in the pathogenesis of MG [41]. However, autoantibodies classified as MIR-directed by competition assay may not necessarily have the same binding mechanisms to nAChR: two MIR-competing autoantibodies may share common or overlapping epitopes or may bind different epitopes but compete through steric effect [14].
Given their established myasthenogenic role, extensive efforts have been put into characterizing the interactions between MG autoantibodies and nAChR using biochemical [45, 46, 48, 49, 50, 51, 52, 53], structural [22, 54, 55, 56], and modeling approaches [57]. More recently, the first crystal structures of human (pdb code: 5HBT) and mouse (pdb code: 5HBV) nAChR ECD bound by the Fab fragment of an EAMG autoantibody, Fab35 were determined [58]. Both crystal structures are very similar, so the discussion here will focus mainly on the human complex (pdb code: 5HBT). The crystal structure, which also contains α-Btx that binds and stabilizes nAChR ECD to facilitate crystallization, shows that Fab35 binds to nAChR α1 in an upright orientation, away from the α-Btx (Figure 2). The Fab35 binding sites on nAChR α1 include the MIR and the N-terminal helix. Fab35 has the canonical IgG antibody structure where the complementarity determining regions (CDRs) from the heavy chain, CDR-H2 and CDR-H3, and the light chain, CDR-L3, form the binding site for nAChR α1. Contacting residues from Fab35 and nAChR α1 (defined as being closer than 4.5 Å) can be mapped using the crystal structure. Such contacting analysis revealed several “hotspots” on nAChR α1 that make numerous contacts to Fab35, including Asn68 and Asp71 from the MIR loop and Arg6 and Lys10 from the N-terminal helix. As shown in Figure 3, each of these four “hotspots” anchors an extensive network of interactions that display remarkable chemical complementarities. The importance of these hotspots are supported by extensive mutagenesis studies [50, 51, 53, 59], which showed that Asn68 and Asp71 of the MIR are essential for MG autoantibody binding, while the surrounding Pro69 and Tyr72, when mutated, also affect the interaction between the antibody and the receptor. Mutation of N68D and D71K in the intact receptor also suggested ASn68 and Asp71 are of vital importance for the interaction [49]. On the N-terminal helix of Torpedo nAChR α1, two exposed residues, Arg6 and Asn10, which correspond to Arg6 and Lys10 in human nAChR α1, respectively, are found to be critical to MG antibody binding by mutational analyses [53]. Many nAChR residues found to be important for antibody binding by mutagenesis studies, including Asn68 and Asp71of the MIR and Arg6 and Lys10 of the N-terminal helix, were indeed found to be interaction “hotspots” at the Fab35/nAChR α1 interface. More recent studies using natively folded nAChR α1α7 chimera proteins [52] or GFP-fused protein fragments [53] showed that the N-terminal helix (residues 1–14) and the nearby loop region (residues 15–32) are also important for high affinity MG antibody binding. These biochemical observations are in excellent agreement with the binding interface structure observed in the crystals (Figure 2).
Crystal structure of the ternary complex of nAChR α1 ECD bound by Fab35 and α-Btx. (a) Ribbon representation of nAChR α1 ECD (α1: cyan) in complex with α-Btx (green) and Fab35 (heavy chain (H, yellow) and light chain (L, magenta)). The variable domains (VH and VL) and the constant domains (CH and CL) of the antibody are indicated accordingly. (b) Surface representation of the ternary complex. (c) Zoomed-in view of the binding interface. The complementarity determining regions of the heavy chain and light chain are indicated as H1, H2, H3, L1, L2, and L3, respectively (Adapted from Noridomi et al. [58]).
Detailed interactions between Fab35 and nAChR α1 ECD at the binding interface. (a) Binding interactions at the vicinity of Asp71 of α1 (located at the MIR). (b) Interactions at the vicinity of Asn68 of α1 (located at the MIR). (c) Interactions involving Arg6 and Lys10 of α1 (located at the N-terminus of α1). (d) Interactions mediated by His3 of α1 (located at the N-terminus of α1) (Adapted from Noridomi et al. [58]).
Although biochemical mapping of antibody-binding residues on nAChR α1 were performed with different antibodies (e.g., mAb210 and mAb132A) [45, 46, 48, 49, 50, 51, 52, 53], it is remarkable that these biochemical data agree so well with the crystal structure. The fact that many MIR residues at the center of the antibody-receptor interface are important for the high affinity binding of a variety of MG antibodies suggests that many MIR-directed autoantibodies share similar binding mechanisms to the core MIR/N-helix region. This is a rather surprising finding given the potential heterogeneity of nAChR antibodies mentioned above. An important implication of this finding is that it may be possible to find small molecule inhibitors to block the binding of a large fraction of pathological MG autoantibodies to nAChR.
To see how various MG/EAMG mAbs may bind nAChR through similar or different mechanisms, we compared the structure of Fab35 with that of two other MG mAbs (Fab198: pdb code 1FN4 and Fab192: pdb code, 1C5D) that have been determined previously [55, 56]. Superposition of the structure of Fab198 and Fab35 from the ternary complex shows that these two Fabs share a similar antigen-binding site (Figure 4a). As such, the MIR loop fits snugly into the pocket formed by the CDR-H2, CDR-H3 and CDR-L3 loops of Fab198, as predicated by previous modeling studies [57]. The CDR-H2 loop of Fab198 is also in a position to interact with the N-terminal α-helix adjacent to the MIR (Figure 4b). Even more remarkably, many key α1-binding residues in Fab35 are also conserved in Fab198 and they appear to have similar contacts to nAChR α1 in the modeled Fab198/nAChR α1 binding interface (Figure 4b). These residues include Trp47 from CDR-H2, Arg50 from CDR-H2, and Tyr95 from CDR-L3 at the center of the MIR-binding pocket, and Trp52 and Asp54 (both from CDR-H2) which interact with the N-terminal α-helix. In contrast to the structural similarities shown above, the CDR-H3 loops between Fab198 and Fab35 differ significantly in length and sequence. The CDR-H3 loop of Fab198 is too short to interact with the surface pocket of nAChR α1, which is occupied by the corresponding CDR-H3 loop of Fab35 in the complex crystal structure (Figure 4b). These structural analyses suggest that mAb35 and mAb198 share a high degree of similarity in binding mechanism to the core MIR/N-terminal helix region but differ in the periphery of the binding interface. On the other hand, superposition of the structure of Fab192 onto that of Fab35 in the ternary complex reveals substantial differences (not shown here). The variable domains (VH and VL) have a significant rotational twist, such that the MIR loop does not fit into the antigen-binding site of Fab192. What is more, the key α1-binding residues of Fab35, like Arg50 and Trp52 of CDR-H2, are not conserved in Fab192. These structural differences suggest that Fab192 may differ significantly from Fab35 in terms of binding mechanisms to nAChR α1, confirming and extending the differences previously recognized between the two [52].
Structural comparisons among MG mAbs. (a) Superposition of Fab198 [55] (heavy chain: purple and light chain: dark green) onto Fab35 in the Fab35/nAChR α1/α-Btx ternary complex using the Cα backbone. (b) Detailed comparison of the binding interface. The residues are colored according to their protein subunits.
A number of studies showed that the total amount of nAChR antibodies in the serum of MG patients does not seem to correlate with disease severity, suggesting that various nAChR antibodies that bind different regions on nAChR may contribute differently to this disease [41, 60, 61, 62]. As discussed above, the total amount of autoantibody from MG patients directed to the MIR of nAChR α1 subunit did show significant correlation with disease severity [47]. These observations suggest that autoantibodies directed to nAChR α1 MIR play a major role in the pathogenesis of MG [41]. It is now clear that many MIR-directed autoantibodies bind a composite epitope consisting of the original MIR (α1, 67–76) and the N-terminal helix (α1, 2–14) (N-helix) and surrounding regions (α1, 15–32). The structural analyses above and published biochemical data suggest that some MIR-directed autoantibodies (e.g., mAb35 and mAb198) bind epitopes centered around the MIR/N-helix core region while others (e.g., mAb192) seems to require epitopes outside the MIR/N-helix core. Nevertheless, based on crystallography studies and structure-guided analyses of existing biochemical data, it can be concluded that despite the heterogeneity of MG autoantibody repertoire a large fraction of MG autoantibodies share a highly-conserved binding mechanism to a core region on the nAChR, suggesting that it is possible to use a single or a limited set of small molecules to block the binding of a large fraction of MG autoantibodies. Because MG autoantibodies directed to the MIR region on nAChR are most relevant to the MG disease, MIR and its surrounding region are therefore an attractive target site for developing small molecules to block the binding of MG autoantibodies. Blocking the binding of MG autoantibodies to nAChR will likely have a direct impact on the antibody-mediated pathologies and may even alter the long-term immune response to nAChR in MG patient.
Targeting protein-protein interface for drug development is generally more challenging than the enzyme active sites [63]. This is especially true for flat protein interfaces lacking features for small molecule binding. However, successes have been achieved with a number of well-known targets, including the p53/MDM2 complex [64], the Bcl-xL/Bak complex [65] and the IL2/IL2R complex [66, 67]. A common feature of these complexes is that the protein-protein binding interfaces contain concave pockets lined with hydrophobic residues, which may provide favorable anchoring points for small molecules to bind and compete with protein-protein interactions. The crystal structure of the Fab35/nAChR α1 complex revealed that their binding interface is characterized by mutual insertions of loops into the pockets of binding partners. On the receptor side (Figure 5), the MIR loop inserts deeply into a surface pocket between VH and VL, and the N-terminal α-helix sits into a groove on the surface of VH. On the antibody side (Figure 6), the CDR-H3 protrudes into a surface pocket formed by the N-terminal α-helix, the loop following the N-terminal α-helix, the MIR and the loop preceding the MIR (referred to as the CDRH3 pocket here after). Based on these structural features, two MG inhibitor design strategies can be envisioned. One is to find small molecules that bind the surface pockets on Fab35 (Figure 5). But this approach faces the potential issue of antibody heterogeneity in sera of human MG patients because small molecule inhibitors may bind some but not other pathological autoantibodies, as it is highly possible antibodies binding to the same epitope may have subtle differences in their antigen-binding site structures. Another approach is to find small molecules to bind the CDRH3 pocket on nAChR (Figure 6). Small molecules bound to this site will directly interfere with the binding of mAB35 by competing with its CDR-H3. Even for other mAbs with short CDR-H3, such as mAb198, the compounds may also block the binding of CDR-H3 through steric hindrances. Moreover, since the CDRH3 pocket is immediate adjacent (about 6–8 Å) (Figure 6) to the MIR/N-helix core region critical for the binding of a large group of MG autoantibodies, compounds bound to CDRH3 could sterically and/or allosterically inhibit the binding of most pathological MG autoantibodies efficiently. Because of its concaved structure, CDRH3 pocket could serve as the anchoring point to design and/or screen small molecules that bind nAChR α1 and complete with MG autoantibodies directed to MIR and its nearby regions.
Surface pockets on Fab35 bound by the nAChR MIR loop (white dashed circle) and the N-terminal helix (black dashed circle).
The surface pocket (green dashed circle) on nAChR α1 bound by the CDR-H3 loop from Fab35 (indicated as H3 in the figure).
The fact that pathogenic B cell clones can populate for a long time in patients’ body may explain why MG is usually a chronic disease. Ectopic germinal centers are found in the thymus of many MG patients who are diagnosed with thymoma or thymus hyperplasia, where nAChR-specific B lymphocyte are constantly activated, selected and matured to produce the antibody, leading to the disease [68]. This disease model underlies the rationale of thymectomy as a widely adopted treatment of MG, but the result varies depending on the subtype of the disease, with a complete remission rate of 25–53% [69]. These results suggest there are possibly other unknown sites where nAChR specific B cells are activated, selected and matured [13].
Using B cell surface marker CD20 [70, 71, 72] or possibly CD19 [73] as the target, disease-causing B cells can be depleted at the cost of killing normal B cells. For example, an ongoing clinical trial, NCT02110706, is testing if rituximab, which targets CD20 on B cells, can be a safe and beneficial therapeutics for MG. In general, treatment with B cell depletion agent often requires a long recovery time before B cells return to normal level again [71]. Moreover, the treatment has been reported to have a short effective duration time for MuSK-positive MG [74]. Long-term usage of such agent may compromise immunological function with increased risk of infection such as Progressive multifocal leukoencephalopathy (PML) and malignancy [72]. As such, strategies targeting nAChR specific B cells seem to be attractive. Since each B cell expresses B cell Receptors of the same idiotype as its secreted antibody on its surface, one can use such property to specifically target autoreactive B cell as long as the antigenicity of the autoimmune disease is clear. The idea was borrowed from immunotoxins [75] in which an antigen-toxin chimera was constructed. The antigen moiety is used to target the B cells that express the BCR of the same idiotype as the antibody and the toxin moiety is responsible for conveying death signal to the target B cells. In a pioneering study in 1983 the author fused thymoglobulin with ricin to treat an autoimmune disorder-Hashimoto’s thyroiditis [76]. Another attempt was tried a decade later in another autoimmune disease-Pemphigus Vulgaris, in which the authors constructed antigen-toxin fusion protein that can specifically target Dsg3-specific hybridoma cells [77]. Similar strategies have also been attempted in the treatment of MG. In a study of 2006, the author fused the nAChR α1 ECD to a plant toxin and showed its effectiveness in specifically killing of α1-specific B cells [78]. More recently, researchers have developed a variant of such strategy in which nAChR α1 ECD was fused with Fc domain of antibody, which was used to convey the negative signal, since B cells express and only express one kind of Fc receptor, namely FcRγIIB, which transduce negative signal for B cell activation. Consequently, such chimeric protein will specifically target the nAChR α1 specific B cell via the binding to the BCR and deliver negative signal to inhibit α1 specific B cells [79, 80].
The idea of antigen-chimera in the treatment of MG seems attractive but will not be practical unless the chimeric protein is stable enough to be used as a therapeutic agent. As mentioned above, nAChR α1 is just one subunit of the nAChR pentamer and is intrinsically unstable, making the expression of wild type nAChR α1 ECD in stable soluble form very challenging. However, as discussed earlier in this chapter, crystallography studies of nAChR α1 ECD in recent years have accumulated extensive experience and knowledge in designing strategic mutations to improve the stability and expression level of nAChR α1 ECD protein while preserve the binding of MIR-directed MG autoantibodies [22, 31, 58] These progresses will greatly facilitate the approach to using engineered antigen chimera to specially inhibit and eliminate nAChR-specific B cells for MG treatment.
Insights from structural studies and molecular biology/biochemical analyses may ultimately lead to precision medicine and personalized treatment of MG by antigen profiling of patient and the use of corresponding molecular missiles to eliminate antigen specific antibodies or B-cells, induce antigen specific tolerance, or blocking nAChR-autoantibody binding by small molecules. These approaches, once established in the treatment of MG, could be expanded to other autoimmune diseases with well-defined antigen targets.
Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.
",metaTitle:"IntechOpen Women in Science Program",metaDescription:"Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"At IntechOpen, we’re laying the foundations for the future by publishing the best research by women in STEM – Open Access and available to all. Our Women in Science program already includes six books in progress by award-winning women scientists on topics ranging from physics to robotics, medicine to environmental science. Our editors come from all over the globe and include L’Oreal–UNESCO For Women in Science award-winners and National Science Foundation and European Commission grant recipients.
\\n\\nWe aim to publish 100 books in our Women in Science program over the next three years. We are looking for books written, edited, or co-edited by women. Contributing chapters by men are welcome. As always, the quality of the research we publish is paramount.
\\n\\nAll project proposals go through a two-stage peer review process and are selected based on the following criteria:
\\n\\nPlus, we want this project to have an impact beyond scientific circles. We will publicize the research in the Women in Science program for a wider general audience through:
\\n\\nInterested? If you have an idea for an edited volume or a monograph, we’d love to hear from you! Contact Ana Pantar at book.idea@intechopen.com.
\\n\\n“My scientific path has given me the opportunity to work with colleagues all over Europe, including Germany, France, and Norway. Editing the book Graph Theory: Advanced Algorithms and Applications with IntechOpen emphasized for me the importance of providing valuable, Open Access literature to our scientific colleagues around the world. So I am highly enthusiastic about the Women in Science book collection, which will highlight the outstanding accomplishments of women scientists and encourage others to walk the challenging path to becoming a recognized scientist." Beril Sirmacek, TU Delft, The Netherlands
\\n\\nAdvantages of Publishing with IntechOpen
\\n\\n\\n"}]'},components:[{type:"htmlEditorComponent",content:'At IntechOpen, we’re laying the foundations for the future by publishing the best research by women in STEM – Open Access and available to all. Our Women in Science program already includes six books in progress by award-winning women scientists on topics ranging from physics to robotics, medicine to environmental science. Our editors come from all over the globe and include L’Oreal–UNESCO For Women in Science award-winners and National Science Foundation and European Commission grant recipients.
\n\nWe aim to publish 100 books in our Women in Science program over the next three years. We are looking for books written, edited, or co-edited by women. Contributing chapters by men are welcome. As always, the quality of the research we publish is paramount.
\n\nAll project proposals go through a two-stage peer review process and are selected based on the following criteria:
\n\nPlus, we want this project to have an impact beyond scientific circles. We will publicize the research in the Women in Science program for a wider general audience through:
\n\nInterested? If you have an idea for an edited volume or a monograph, we’d love to hear from you! Contact Ana Pantar at book.idea@intechopen.com.
\n\n“My scientific path has given me the opportunity to work with colleagues all over Europe, including Germany, France, and Norway. Editing the book Graph Theory: Advanced Algorithms and Applications with IntechOpen emphasized for me the importance of providing valuable, Open Access literature to our scientific colleagues around the world. So I am highly enthusiastic about the Women in Science book collection, which will highlight the outstanding accomplishments of women scientists and encourage others to walk the challenging path to becoming a recognized scientist." Beril Sirmacek, TU Delft, The Netherlands
\n\n\n\n\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:null},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5313},{group:"region",caption:"Middle and South America",value:2,count:4819},{group:"region",caption:"Africa",value:3,count:1468},{group:"region",caption:"Asia",value:4,count:9363},{group:"region",caption:"Australia and Oceania",value:5,count:837},{group:"region",caption:"Europe",value:6,count:14778}],offset:12,limit:12,total:108153},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish"},books:[{type:"book",id:"10100",title:"Evo-Devo",subtitle:null,isOpenForSubmission:!0,hash:"4c17ab0c64ce206c75ad6cec64e05737",slug:null,bookSignature:"Dr. Dimitrios P. Vlachakis, Prof. Elias Eliopoulos and Prof. George P. Chrousos",coverURL:"https://cdn.intechopen.com/books/images_new/10100.jpg",editedByType:null,editors:[{id:"179110",title:"Dr.",name:"Dimitrios",surname:"Vlachakis",slug:"dimitrios-vlachakis",fullName:"Dimitrios Vlachakis"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7845",title:"Platelets",subtitle:null,isOpenForSubmission:!0,hash:"d33b20516d6ff3a5b7446a882109ba26",slug:null,bookSignature:"Dr. Steve W. W. Kerrigan and Prof. Niamh Moran",coverURL:"https://cdn.intechopen.com/books/images_new/7845.jpg",editedByType:null,editors:[{id:"73961",title:"Dr.",name:"Steve W.",surname:"Kerrigan",slug:"steve-w.-kerrigan",fullName:"Steve W. Kerrigan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7965",title:"Display Technology",subtitle:null,isOpenForSubmission:!0,hash:"eb83772cea6200bdd685b8a1b93ee35d",slug:null,bookSignature:"Dr. In Byeong Kang",coverURL:"https://cdn.intechopen.com/books/images_new/7965.jpg",editedByType:null,editors:[{id:"241133",title:"Dr.",name:"In Byeong",surname:"Kang",slug:"in-byeong-kang",fullName:"In Byeong Kang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9280",title:"Underwater Work",subtitle:null,isOpenForSubmission:!0,hash:"647b4270d937deae4a82f5702d1959ec",slug:null,bookSignature:"Dr. Sérgio António Neves Lousada",coverURL:"https://cdn.intechopen.com/books/images_new/9280.jpg",editedByType:null,editors:[{id:"248645",title:"Dr.",name:"Sérgio António",surname:"Neves Lousada",slug:"sergio-antonio-neves-lousada",fullName:"Sérgio António Neves Lousada"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6837",title:"Lithium-ion Batteries - Thin Film for Energy Materials and Devices",subtitle:null,isOpenForSubmission:!0,hash:"ea7789260b319b9a4b472257f57bfeb5",slug:null,bookSignature:"Prof. Mitsunobu Sato, Dr. Li Lu and Dr. Hiroki Nagai",coverURL:"https://cdn.intechopen.com/books/images_new/6837.jpg",editedByType:null,editors:[{id:"179615",title:"Prof.",name:"Mitsunobu",surname:"Sato",slug:"mitsunobu-sato",fullName:"Mitsunobu Sato"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9212",title:"Titration Technique",subtitle:null,isOpenForSubmission:!0,hash:"5278b500d19d2508a7c933276167d82c",slug:null,bookSignature:"Associate Prof. Vu Dang Hoang",coverURL:"https://cdn.intechopen.com/books/images_new/9212.jpg",editedByType:null,editors:[{id:"199907",title:"Associate Prof.",name:"Vu Dang",surname:"Hoang",slug:"vu-dang-hoang",fullName:"Vu Dang Hoang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9423",title:"Applications of Artificial Intelligence in Process Industry Automation, Heat and Power Generation and Smart Manufacturing",subtitle:null,isOpenForSubmission:!0,hash:"10ac8fb0bdbf61044395963028653d21",slug:null,bookSignature:"Prof. Konstantinos G. Kyprianidis and Prof. Erik Dahlquist",coverURL:"https://cdn.intechopen.com/books/images_new/9423.jpg",editedByType:null,editors:[{id:"35868",title:"Prof.",name:"Konstantinos",surname:"Kyprianidis",slug:"konstantinos-kyprianidis",fullName:"Konstantinos Kyprianidis"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9428",title:"New Trends in the Use of Artificial Intelligence for the Industry 4.0",subtitle:null,isOpenForSubmission:!0,hash:"9e089eec484ce8e9eb32198c2d8b34ea",slug:null,bookSignature:"Dr. Luis Romeral Martinez, Dr. Roque A. Osornio-Rios and Dr. Miguel Delgado Prieto",coverURL:"https://cdn.intechopen.com/books/images_new/9428.jpg",editedByType:null,editors:[{id:"86501",title:"Dr.",name:"Luis",surname:"Romeral Martinez",slug:"luis-romeral-martinez",fullName:"Luis Romeral Martinez"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8968",title:"Molecular and Metabolic Alterations in Tumorigenesis",subtitle:null,isOpenForSubmission:!0,hash:"e3c27ac25ffa58c82beeb2b70147b9bf",slug:null,bookSignature:"Dr. Yasemin Basbinar and Dr. Gizem Calibasi Kocal",coverURL:"https://cdn.intechopen.com/books/images_new/8968.jpg",editedByType:null,editors:[{id:"242097",title:"Dr.",name:"Yasemin",surname:"Basbinar",slug:"yasemin-basbinar",fullName:"Yasemin Basbinar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8031",title:"Pavement Engineering",subtitle:null,isOpenForSubmission:!0,hash:"1d8ae1b3b3a208c2b16c1ff852e14207",slug:null,bookSignature:"Dr. Sameh Zaghloul",coverURL:"https://cdn.intechopen.com/books/images_new/8031.jpg",editedByType:null,editors:[{id:"269407",title:"Dr.",name:"Sameh",surname:"Zaghloul",slug:"sameh-zaghloul",fullName:"Sameh Zaghloul"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7997",title:"Autophagy in Injury, Infection and Cancer Diseases",subtitle:null,isOpenForSubmission:!0,hash:"3daed6048bc8ff8368c4279558f109d7",slug:null,bookSignature:"Dr. Nikolai Gorbunov",coverURL:"https://cdn.intechopen.com/books/images_new/7997.jpg",editedByType:null,editors:[{id:"180960",title:"Dr.",name:"Nikolai",surname:"Gorbunov",slug:"nikolai-gorbunov",fullName:"Nikolai Gorbunov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9010",title:"Ion Channel Dysfunction in Disease",subtitle:null,isOpenForSubmission:!0,hash:"2bc87751cc961a9d348958e2ebb8b3a7",slug:null,bookSignature:"Dr. Saverio Gentile",coverURL:"https://cdn.intechopen.com/books/images_new/9010.jpg",editedByType:null,editors:[{id:"181463",title:"Dr.",name:"Saverio",surname:"Gentile",slug:"saverio-gentile",fullName:"Saverio Gentile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:34},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:33},{group:"topic",caption:"Business, Management and Economics",value:7,count:10},{group:"topic",caption:"Chemistry",value:8,count:30},{group:"topic",caption:"Computer and Information Science",value:9,count:25},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:15},{group:"topic",caption:"Engineering",value:11,count:74},{group:"topic",caption:"Environmental Sciences",value:12,count:13},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:38},{group:"topic",caption:"Mathematics",value:15,count:14},{group:"topic",caption:"Medicine",value:16,count:137},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:6},{group:"topic",caption:"Neuroscience",value:18,count:6},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:8},{group:"topic",caption:"Physics",value:20,count:20},{group:"topic",caption:"Psychology",value:21,count:2},{group:"topic",caption:"Robotics",value:22,count:6},{group:"topic",caption:"Social Sciences",value:23,count:13},{group:"topic",caption:"Technology",value:24,count:10},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:3},{group:"topic",caption:"Genesiology",value:300,count:1},{group:"topic",caption:"Machine Learning and Data Mining",value:521,count:1},{group:"topic",caption:"Intelligent System",value:535,count:1}],offset:12,limit:12,total:505},popularBooks:{featuredBooks:[{type:"book",id:"7878",title:"Advances in Extracorporeal Membrane Oxygenation",subtitle:"Volume 3",isOpenForSubmission:!1,hash:"f95bf990273d08098a00f9a1c2403cbe",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",bookSignature:"Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/7878.jpg",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8299",title:"Timber Buildings and Sustainability",subtitle:null,isOpenForSubmission:!1,hash:"bccf2891cec38ed041724131aa34c25a",slug:"timber-buildings-and-sustainability",bookSignature:"Giovanna Concu",coverURL:"https://cdn.intechopen.com/books/images_new/8299.jpg",editors:[{id:"108709",title:"Dr.",name:"Giovanna",middleName:null,surname:"Concu",slug:"giovanna-concu",fullName:"Giovanna Concu"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7614",title:"Fourier Transforms",subtitle:"Century of Digitalization and Increasing Expectations",isOpenForSubmission:!1,hash:"ff3501657ae983a3b42fef1f7058ac91",slug:"fourier-transforms-century-of-digitalization-and-increasing-expectations",bookSignature:"Goran S. Nikoli? and Dragana Z. Markovi?-Nikoli?",coverURL:"https://cdn.intechopen.com/books/images_new/7614.jpg",editors:[{id:"23261",title:"Prof.",name:"Goran",middleName:"S.",surname:"Nikolic",slug:"goran-nikolic",fullName:"Goran Nikolic"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7062",title:"Rhinosinusitis",subtitle:null,isOpenForSubmission:!1,hash:"14ed95e155b1e57a61827ca30b579d09",slug:"rhinosinusitis",bookSignature:"Balwant Singh Gendeh and Mirjana Turkalj",coverURL:"https://cdn.intechopen.com/books/images_new/7062.jpg",editors:[{id:"67669",title:"Prof.",name:"Balwant Singh",middleName:null,surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7087",title:"Tendons",subtitle:null,isOpenForSubmission:!1,hash:"786abac0445c102d1399a1e727a2db7f",slug:"tendons",bookSignature:"Hasan Sözen",coverURL:"https://cdn.intechopen.com/books/images_new/7087.jpg",editors:[{id:"161402",title:"Dr.",name:"Hasan",middleName:null,surname:"Sözen",slug:"hasan-sozen",fullName:"Hasan Sözen"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7955",title:"Advances in Hematologic Malignancies",subtitle:null,isOpenForSubmission:!1,hash:"59ca1b09447fab4717a93e099f646d28",slug:"advances-in-hematologic-malignancies",bookSignature:"Gamal Abdul Hamid",coverURL:"https://cdn.intechopen.com/books/images_new/7955.jpg",editors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7701",title:"Assistive and Rehabilitation Engineering",subtitle:null,isOpenForSubmission:!1,hash:"4191b744b8af3b17d9a80026dcb0617f",slug:"assistive-and-rehabilitation-engineering",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7701.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7837",title:"Geriatric Medicine and Gerontology",subtitle:null,isOpenForSubmission:!1,hash:"e277d005b23536bcd9f8550046101979",slug:"geriatric-medicine-and-gerontology",bookSignature:"Edward T. Zawada Jr.",coverURL:"https://cdn.intechopen.com/books/images_new/7837.jpg",editors:[{id:"16344",title:"Dr.",name:"Edward T.",middleName:null,surname:"Zawada Jr.",slug:"edward-t.-zawada-jr.",fullName:"Edward T. Zawada Jr."}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,isOpenForSubmission:!1,hash:"61c627da05b2ace83056d11357bdf361",slug:"current-topics-in-neglected-tropical-diseases",bookSignature:"Alfonso J. Rodriguez-Morales",coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",editors:[{id:"131400",title:"Dr.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7610",title:"Renewable and Sustainable Composites",subtitle:null,isOpenForSubmission:!1,hash:"c2de26c3d329c54f093dc3f05417500a",slug:"renewable-and-sustainable-composites",bookSignature:"António B. Pereira and Fábio A. O. Fernandes",coverURL:"https://cdn.intechopen.com/books/images_new/7610.jpg",editors:[{id:"211131",title:"Prof.",name:"António",middleName:"Bastos",surname:"Pereira",slug:"antonio-pereira",fullName:"António Pereira"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8416",title:"Non-Equilibrium Particle Dynamics",subtitle:null,isOpenForSubmission:!1,hash:"2c3add7639dcd1cb442cb4313ea64e3a",slug:"non-equilibrium-particle-dynamics",bookSignature:"Albert S. Kim",coverURL:"https://cdn.intechopen.com/books/images_new/8416.jpg",editors:[{id:"21045",title:"Prof.",name:"Albert S.",middleName:null,surname:"Kim",slug:"albert-s.-kim",fullName:"Albert S. Kim"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8008",title:"Antioxidants",subtitle:null,isOpenForSubmission:!1,hash:"76361b4061e830906267933c1c670027",slug:"antioxidants",bookSignature:"Emad Shalaby",coverURL:"https://cdn.intechopen.com/books/images_new/8008.jpg",editors:[{id:"63600",title:"Prof.",name:"Emad",middleName:null,surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby"}],productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:4396},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"7878",title:"Advances in Extracorporeal Membrane Oxygenation",subtitle:"Volume 3",isOpenForSubmission:!1,hash:"f95bf990273d08098a00f9a1c2403cbe",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",bookSignature:"Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/7878.jpg",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8299",title:"Timber Buildings and Sustainability",subtitle:null,isOpenForSubmission:!1,hash:"bccf2891cec38ed041724131aa34c25a",slug:"timber-buildings-and-sustainability",bookSignature:"Giovanna Concu",coverURL:"https://cdn.intechopen.com/books/images_new/8299.jpg",editors:[{id:"108709",title:"Dr.",name:"Giovanna",middleName:null,surname:"Concu",slug:"giovanna-concu",fullName:"Giovanna Concu"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7614",title:"Fourier Transforms",subtitle:"Century of Digitalization and Increasing Expectations",isOpenForSubmission:!1,hash:"ff3501657ae983a3b42fef1f7058ac91",slug:"fourier-transforms-century-of-digitalization-and-increasing-expectations",bookSignature:"Goran S. Nikoli? and Dragana Z. Markovi?-Nikoli?",coverURL:"https://cdn.intechopen.com/books/images_new/7614.jpg",editors:[{id:"23261",title:"Prof.",name:"Goran",middleName:"S.",surname:"Nikolic",slug:"goran-nikolic",fullName:"Goran Nikolic"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7062",title:"Rhinosinusitis",subtitle:null,isOpenForSubmission:!1,hash:"14ed95e155b1e57a61827ca30b579d09",slug:"rhinosinusitis",bookSignature:"Balwant Singh Gendeh and Mirjana Turkalj",coverURL:"https://cdn.intechopen.com/books/images_new/7062.jpg",editors:[{id:"67669",title:"Prof.",name:"Balwant Singh",middleName:null,surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7087",title:"Tendons",subtitle:null,isOpenForSubmission:!1,hash:"786abac0445c102d1399a1e727a2db7f",slug:"tendons",bookSignature:"Hasan Sözen",coverURL:"https://cdn.intechopen.com/books/images_new/7087.jpg",editors:[{id:"161402",title:"Dr.",name:"Hasan",middleName:null,surname:"Sözen",slug:"hasan-sozen",fullName:"Hasan Sözen"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7955",title:"Advances in Hematologic Malignancies",subtitle:null,isOpenForSubmission:!1,hash:"59ca1b09447fab4717a93e099f646d28",slug:"advances-in-hematologic-malignancies",bookSignature:"Gamal Abdul Hamid",coverURL:"https://cdn.intechopen.com/books/images_new/7955.jpg",editors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7701",title:"Assistive and Rehabilitation Engineering",subtitle:null,isOpenForSubmission:!1,hash:"4191b744b8af3b17d9a80026dcb0617f",slug:"assistive-and-rehabilitation-engineering",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7701.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7837",title:"Geriatric Medicine and Gerontology",subtitle:null,isOpenForSubmission:!1,hash:"e277d005b23536bcd9f8550046101979",slug:"geriatric-medicine-and-gerontology",bookSignature:"Edward T. Zawada Jr.",coverURL:"https://cdn.intechopen.com/books/images_new/7837.jpg",editors:[{id:"16344",title:"Dr.",name:"Edward T.",middleName:null,surname:"Zawada Jr.",slug:"edward-t.-zawada-jr.",fullName:"Edward T. Zawada Jr."}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,isOpenForSubmission:!1,hash:"61c627da05b2ace83056d11357bdf361",slug:"current-topics-in-neglected-tropical-diseases",bookSignature:"Alfonso J. Rodriguez-Morales",coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",editors:[{id:"131400",title:"Dr.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7610",title:"Renewable and Sustainable Composites",subtitle:null,isOpenForSubmission:!1,hash:"c2de26c3d329c54f093dc3f05417500a",slug:"renewable-and-sustainable-composites",bookSignature:"António B. Pereira and Fábio A. O. Fernandes",coverURL:"https://cdn.intechopen.com/books/images_new/7610.jpg",editors:[{id:"211131",title:"Prof.",name:"António",middleName:"Bastos",surname:"Pereira",slug:"antonio-pereira",fullName:"António Pereira"}],productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8463",title:"Pediatric Surgery, Flowcharts and Clinical Algorithms",subtitle:null,isOpenForSubmission:!1,hash:"23f39beea4d557b0ae424e2eaf82bf5e",slug:"pediatric-surgery-flowcharts-and-clinical-algorithms",bookSignature:"Sameh Shehata",coverURL:"https://cdn.intechopen.com/books/images_new/8463.jpg",editedByType:"Edited by",editors:[{id:"37518",title:"Prof.",name:"Sameh",middleName:null,surname:"Shehata",slug:"sameh-shehata",fullName:"Sameh Shehata"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7187",title:"Osteosarcoma",subtitle:"Diagnosis, Mechanisms, and Translational Developments",isOpenForSubmission:!1,hash:"89096359b754beb806eca4c6d8aacaba",slug:"osteosarcoma-diagnosis-mechanisms-and-translational-developments",bookSignature:"Matthew Gregory Cable and Robert Lawrence Randall",coverURL:"https://cdn.intechopen.com/books/images_new/7187.jpg",editedByType:"Edited by",editors:[{id:"265693",title:"Dr.",name:"Matthew Gregory",middleName:null,surname:"Cable",slug:"matthew-gregory-cable",fullName:"Matthew Gregory Cable"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7955",title:"Advances in Hematologic Malignancies",subtitle:null,isOpenForSubmission:!1,hash:"59ca1b09447fab4717a93e099f646d28",slug:"advances-in-hematologic-malignancies",bookSignature:"Gamal Abdul Hamid",coverURL:"https://cdn.intechopen.com/books/images_new/7955.jpg",editedByType:"Edited by",editors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7701",title:"Assistive and Rehabilitation Engineering",subtitle:null,isOpenForSubmission:!1,hash:"4191b744b8af3b17d9a80026dcb0617f",slug:"assistive-and-rehabilitation-engineering",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7701.jpg",editedByType:"Edited by",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"e7ea7e74ce7a7a8e5359629e07c68d31",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",editedByType:"Edited by",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8256",title:"Distillation",subtitle:"Modelling, Simulation and Optimization",isOpenForSubmission:!1,hash:"c76af109f83e14d915e5cb3949ae8b80",slug:"distillation-modelling-simulation-and-optimization",bookSignature:"Vilmar Steffen",coverURL:"https://cdn.intechopen.com/books/images_new/8256.jpg",editedByType:"Edited by",editors:[{id:"189035",title:"Dr.",name:"Vilmar",middleName:null,surname:"Steffen",slug:"vilmar-steffen",fullName:"Vilmar Steffen"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7240",title:"Growing and Handling of Bacterial Cultures",subtitle:null,isOpenForSubmission:!1,hash:"a76c3ef7718c0b72d0128817cdcbe6e3",slug:"growing-and-handling-of-bacterial-cultures",bookSignature:"Madhusmita Mishra",coverURL:"https://cdn.intechopen.com/books/images_new/7240.jpg",editedByType:"Edited by",editors:[{id:"204267",title:"Dr.",name:"Madhusmita",middleName:null,surname:"Mishra",slug:"madhusmita-mishra",fullName:"Madhusmita Mishra"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8299",title:"Timber Buildings and Sustainability",subtitle:null,isOpenForSubmission:!1,hash:"bccf2891cec38ed041724131aa34c25a",slug:"timber-buildings-and-sustainability",bookSignature:"Giovanna Concu",coverURL:"https://cdn.intechopen.com/books/images_new/8299.jpg",editedByType:"Edited by",editors:[{id:"108709",title:"Dr.",name:"Giovanna",middleName:null,surname:"Concu",slug:"giovanna-concu",fullName:"Giovanna Concu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7062",title:"Rhinosinusitis",subtitle:null,isOpenForSubmission:!1,hash:"14ed95e155b1e57a61827ca30b579d09",slug:"rhinosinusitis",bookSignature:"Balwant Singh Gendeh and Mirjana Turkalj",coverURL:"https://cdn.intechopen.com/books/images_new/7062.jpg",editedByType:"Edited by",editors:[{id:"67669",title:"Prof.",name:"Balwant Singh",middleName:null,surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7837",title:"Geriatric Medicine and Gerontology",subtitle:null,isOpenForSubmission:!1,hash:"e277d005b23536bcd9f8550046101979",slug:"geriatric-medicine-and-gerontology",bookSignature:"Edward T. Zawada Jr.",coverURL:"https://cdn.intechopen.com/books/images_new/7837.jpg",editedByType:"Edited by",editors:[{id:"16344",title:"Dr.",name:"Edward T.",middleName:null,surname:"Zawada Jr.",slug:"edward-t.-zawada-jr.",fullName:"Edward T. Zawada Jr."}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"79",title:"Sustainable Development",slug:"business-management-and-economics-sustainable-development",parent:{title:"Business, Management and Economics",slug:"business-management-and-economics"},numberOfBooks:4,numberOfAuthorsAndEditors:69,numberOfWosCitations:11,numberOfCrossrefCitations:16,numberOfDimensionsCitations:47,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"business-management-and-economics-sustainable-development",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"6823",title:"Sustainability Assessment and Reporting",subtitle:null,isOpenForSubmission:!1,hash:"4db72204a34eff9b5143955463b293cf",slug:"sustainability-assessment-and-reporting",bookSignature:"Soner Gokten and Pinar Okan Gokten",coverURL:"https://cdn.intechopen.com/books/images_new/6823.jpg",editedByType:"Edited by",editors:[{id:"70354",title:"Ph.D.",name:"Soner",middleName:null,surname:"Gokten",slug:"soner-gokten",fullName:"Soner Gokten"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5704",title:"Skills Development for Sustainable Manufacturing",subtitle:null,isOpenForSubmission:!1,hash:"5d9994c97da570ef318b4da424f8cce0",slug:"skills-development-for-sustainable-manufacturing",bookSignature:"Christianah Olakitan Ijagbemi and Harold Moody Campbell",coverURL:"https://cdn.intechopen.com/books/images_new/5704.jpg",editedByType:"Edited by",editors:[{id:"192754",title:"Dr.",name:"Christianah",middleName:null,surname:"Ijagbemi",slug:"christianah-ijagbemi",fullName:"Christianah Ijagbemi"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2205",title:"Globalization and Responsibility",subtitle:null,isOpenForSubmission:!1,hash:"46d98262d7d3b53c695cd7bc87f00040",slug:"globalization-and-responsibility",bookSignature:"Zlatan Delic",coverURL:"https://cdn.intechopen.com/books/images_new/2205.jpg",editedByType:"Edited by",editors:[{id:"31746",title:"Dr.",name:"Zlatan",middleName:null,surname:"Delic",slug:"zlatan-delic",fullName:"Zlatan Delic"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2015",title:"Sustainable Development",subtitle:"Education, Business and Management - Architecture and Building Construction - Agriculture and Food Security",isOpenForSubmission:!1,hash:"7d2fbda1c194835efdcee1c4c58291b7",slug:"sustainable-development-education-business-and-management-architecture-and-building-construction-agriculture-and-food-security",bookSignature:"Chaouki Ghenai",coverURL:"https://cdn.intechopen.com/books/images_new/2015.jpg",editedByType:"Edited by",editors:[{id:"14569",title:"Prof.",name:"Chaouki",middleName:null,surname:"Ghenai",slug:"chaouki-ghenai",fullName:"Chaouki Ghenai"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,mostCitedChapters:[{id:"29276",doi:"10.5772/26613",title:"Mapping is a Key for Sustainable Development of Coastal Waters: Examples of Seagrass Beds and Aquaculture Facilities in Japan with Use of ALOS Images",slug:"mapping-is-a-key-for-sustainable-development-of-coastal-waters",totalDownloads:1979,totalCrossrefCites:3,totalDimensionsCites:22,book:{slug:"sustainable-development-education-business-and-management-architecture-and-building-construction-agriculture-and-food-security",title:"Sustainable Development",fullTitle:"Sustainable Development - Education, Business and Management - Architecture and Building Construction - Agriculture and Food Security"},signatures:"Teruhisa Komatsu, Tatsuyuki Sagawa, Shuhei Sawayama, Hideaki Tanoue, Akihiko Mohri and Yoshihiko Sakanishi",authors:[{id:"67315",title:"Dr.",name:"Teruhisa",middleName:null,surname:"Komatsu",slug:"teruhisa-komatsu",fullName:"Teruhisa Komatsu"}]},{id:"29284",doi:"10.5772/28707",title:"Temporal-Spatial Changes of the Oasis in the Heihe River Basin over the Past 25 Years",slug:"spatio-temporal-changes-of-the-heihe-river-basin-oasis-in-northwest-china-over-the-last-25-years",totalDownloads:1277,totalCrossrefCites:2,totalDimensionsCites:3,book:{slug:"sustainable-development-education-business-and-management-architecture-and-building-construction-agriculture-and-food-security",title:"Sustainable Development",fullTitle:"Sustainable Development - Education, Business and Management - Architecture and Building Construction - Agriculture and Food Security"},signatures:"Yaowen Xie, Linlin Li, Xiaojiong Zhao and Chunxia Yuan",authors:[{id:"75065",title:"Prof.",name:"Yaowen",middleName:null,surname:"Xie",slug:"yaowen-xie",fullName:"Yaowen Xie"}]},{id:"29270",doi:"10.5772/27628",title:"Malaysian Primary Pre-Service Teachers’ Understanding and Awareness of Environmental Knowledge",slug:"malaysian-pre-service-teachers-understanding-and-awareness-of-environmental-knowledge",totalDownloads:1917,totalCrossrefCites:3,totalDimensionsCites:3,book:{slug:"sustainable-development-education-business-and-management-architecture-and-building-construction-agriculture-and-food-security",title:"Sustainable Development",fullTitle:"Sustainable Development - Education, Business and Management - Architecture and Building Construction - Agriculture and Food Security"},signatures:"Mageswary Karpudewan and Zurida Ismail",authors:[{id:"70890",title:"Prof.",name:"Zurida",middleName:null,surname:"Ismail",slug:"zurida-ismail",fullName:"Zurida Ismail"},{id:"78144",title:"Dr.",name:"Mageswary",middleName:null,surname:"Karpudewan",slug:"mageswary-karpudewan",fullName:"Mageswary Karpudewan"}]}],mostDownloadedChaptersLast30Days:[{id:"62818",title:"Methodologies for Assessing Sustainability in Farming Systems",slug:"methodologies-for-assessing-sustainability-in-farming-systems",totalDownloads:468,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"sustainability-assessment-and-reporting",title:"Sustainability Assessment and Reporting",fullTitle:"Sustainability Assessment and Reporting"},signatures:"Jaime Fabián Cruz, Yolanda Mena and Vicente Rodríguez-Estévez",authors:[{id:"101973",title:"Dr.",name:"Vicente",middleName:null,surname:"Rodríguez-Estévez",slug:"vicente-rodriguez-estevez",fullName:"Vicente Rodríguez-Estévez"},{id:"256388",title:"Dr.",name:"Yolanda",middleName:null,surname:"Mena",slug:"yolanda-mena",fullName:"Yolanda Mena"},{id:"256393",title:"Ph.D. Student",name:"Fabian",middleName:null,surname:"Cruz",slug:"fabian-cruz",fullName:"Fabian Cruz"}]},{id:"56724",title:"Sustainable Solid Waste Recycling",slug:"sustainable-solid-waste-recycling",totalDownloads:920,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"skills-development-for-sustainable-manufacturing",title:"Skills Development for Sustainable Manufacturing",fullTitle:"Skills Development for Sustainable Manufacturing"},signatures:"Ahmad K. Jassim",authors:[{id:"195227",title:"Dr.",name:"Ahmad",middleName:"K",surname:"Jassim",slug:"ahmad-jassim",fullName:"Ahmad Jassim"}]},{id:"56636",title:"Sustainable Maintenance Practices and Skills for Competitive Production System",slug:"sustainable-maintenance-practices-and-skills-for-competitive-production-system",totalDownloads:769,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"skills-development-for-sustainable-manufacturing",title:"Skills Development for Sustainable Manufacturing",fullTitle:"Skills Development for Sustainable Manufacturing"},signatures:"Adeyeri Michael Kanisuru",authors:[{id:"205337",title:"Dr.",name:"Michael",middleName:null,surname:"Adeyeri",slug:"michael-adeyeri",fullName:"Michael Adeyeri"}]},{id:"57317",title:"Interventions to Skills Development in the Automotive Manufacturing Sector of South Africa",slug:"interventions-to-skills-development-in-the-automotive-manufacturing-sector-of-south-africa",totalDownloads:611,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"skills-development-for-sustainable-manufacturing",title:"Skills Development for Sustainable Manufacturing",fullTitle:"Skills Development for Sustainable Manufacturing"},signatures:"Opeyeolu Timothy Laseinde and Grace Mukondeleli Kanakana",authors:[{id:"197520",title:"Dr.",name:"Opeyeolu Timothy",middleName:null,surname:"Laseinde",slug:"opeyeolu-timothy-laseinde",fullName:"Opeyeolu Timothy Laseinde"},{id:"205076",title:"Dr.",name:"Grace Mukondeleli",middleName:null,surname:"Kanakana",slug:"grace-mukondeleli-kanakana",fullName:"Grace Mukondeleli Kanakana"}]},{id:"37637",title:"Developing Educational Practices in the Globalized World",slug:"developing-educational-practices-in-the-globalized-world",totalDownloads:1873,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"globalization-and-responsibility",title:"Globalization and Responsibility",fullTitle:"Globalization and Responsibility"},signatures:"Maura Striano",authors:[{id:"28386",title:"Prof.",name:"Maura",middleName:null,surname:"Striano",slug:"maura-striano",fullName:"Maura Striano"}]},{id:"29276",title:"Mapping is a Key for Sustainable Development of Coastal Waters: Examples of Seagrass Beds and Aquaculture Facilities in Japan with Use of ALOS Images",slug:"mapping-is-a-key-for-sustainable-development-of-coastal-waters",totalDownloads:1979,totalCrossrefCites:3,totalDimensionsCites:22,book:{slug:"sustainable-development-education-business-and-management-architecture-and-building-construction-agriculture-and-food-security",title:"Sustainable Development",fullTitle:"Sustainable Development - Education, Business and Management - Architecture and Building Construction - Agriculture and Food Security"},signatures:"Teruhisa Komatsu, Tatsuyuki Sagawa, Shuhei Sawayama, Hideaki Tanoue, Akihiko Mohri and Yoshihiko Sakanishi",authors:[{id:"67315",title:"Dr.",name:"Teruhisa",middleName:null,surname:"Komatsu",slug:"teruhisa-komatsu",fullName:"Teruhisa Komatsu"}]},{id:"61998",title:"Using a Social Accounting Matrix for Analysing Institutions’ Income: A Case from Portugal",slug:"using-a-social-accounting-matrix-for-analysing-institutions-income-a-case-from-portugal",totalDownloads:319,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"sustainability-assessment-and-reporting",title:"Sustainability Assessment and Reporting",fullTitle:"Sustainability Assessment and Reporting"},signatures:"Susana Santos",authors:[{id:"244283",title:"Prof.",name:"Susana",middleName:null,surname:"Santos",slug:"susana-santos",fullName:"Susana Santos"}]},{id:"62872",title:"Sustainability Reporting and Income Smoothing: Evidence from Saudi-Listed Companies",slug:"sustainability-reporting-and-income-smoothing-evidence-from-saudi-listed-companies",totalDownloads:280,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"sustainability-assessment-and-reporting",title:"Sustainability Assessment and Reporting",fullTitle:"Sustainability Assessment and Reporting"},signatures:"Lassaad Ben Mahjoub",authors:[{id:"242339",title:"Dr.",name:"Lassaad",middleName:null,surname:"Ben Mahjoub",slug:"lassaad-ben-mahjoub",fullName:"Lassaad Ben Mahjoub"}]},{id:"29275",title:"Sustainable Building in Malaysia: The Development of Sustainable Building Rating System",slug:"sustainable-building-in-malaysia-the-development-of-sustainable-building-rating-system",totalDownloads:8415,totalCrossrefCites:1,totalDimensionsCites:3,book:{slug:"sustainable-development-education-business-and-management-architecture-and-building-construction-agriculture-and-food-security",title:"Sustainable Development",fullTitle:"Sustainable Development - Education, Business and Management - Architecture and Building Construction - Agriculture and Food Security"},signatures:"Ar Zuhairuse MD Darus and Nor Atikah Hashim",authors:[{id:"70881",title:"Prof.",name:"Zuhairuse",middleName:null,surname:"Darus",slug:"zuhairuse-darus",fullName:"Zuhairuse Darus"},{id:"135807",title:"Ms.",name:"Nor Atikah",middleName:null,surname:"Hashim",slug:"nor-atikah-hashim",fullName:"Nor Atikah Hashim"}]},{id:"56899",title:"Designing and Developing New VET Curricula to Address Skills Gaps in the Aeronautics Industry",slug:"designing-and-developing-new-vet-curricula-to-address-skills-gaps-in-the-aeronautics-industry",totalDownloads:393,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"skills-development-for-sustainable-manufacturing",title:"Skills Development for Sustainable Manufacturing",fullTitle:"Skills Development for Sustainable Manufacturing"},signatures:"Rosa Maria Arnaldo Valdés, Victor Fernando Gómez Comendador\nand Alvaro Rodriguez Sanz",authors:[{id:"147777",title:"Dr.",name:"Rosa",middleName:null,surname:"Arnaldo",slug:"rosa-arnaldo",fullName:"Rosa Arnaldo"},{id:"196016",title:"Dr.",name:"Victor Fernando",middleName:null,surname:"Gomez Comendador",slug:"victor-fernando-gomez-comendador",fullName:"Victor Fernando Gomez Comendador"}]}],onlineFirstChaptersFilter:{topicSlug:"business-management-and-economics-sustainable-development",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"6837",title:"Lithium-ion Batteries - Thin Film for Energy Materials and Devices",subtitle:null,isOpenForSubmission:!0,hash:"ea7789260b319b9a4b472257f57bfeb5",slug:null,bookSignature:"Prof. Mitsunobu Sato, Dr. Li Lu and Dr. Hiroki Nagai",coverURL:"https://cdn.intechopen.com/books/images_new/6837.jpg",editedByType:null,editors:[{id:"179615",title:"Prof.",name:"Mitsunobu",middleName:null,surname:"Sato",slug:"mitsunobu-sato",fullName:"Mitsunobu Sato"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9423",title:"Applications of Artificial Intelligence in Process Industry Automation, Heat and Power Generation and Smart Manufacturing",subtitle:null,isOpenForSubmission:!0,hash:"10ac8fb0bdbf61044395963028653d21",slug:null,bookSignature:"Prof. Konstantinos G. Kyprianidis and Prof. Erik Dahlquist",coverURL:"https://cdn.intechopen.com/books/images_new/9423.jpg",editedByType:null,editors:[{id:"35868",title:"Prof.",name:"Konstantinos",middleName:"G.",surname:"Kyprianidis",slug:"konstantinos-kyprianidis",fullName:"Konstantinos Kyprianidis"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9428",title:"New Trends in the Use of Artificial Intelligence for the Industry 4.0",subtitle:null,isOpenForSubmission:!0,hash:"9e089eec484ce8e9eb32198c2d8b34ea",slug:null,bookSignature:"Dr. Luis Romeral Martinez, Dr. Roque A. Osornio-Rios and Dr. Miguel Delgado Prieto",coverURL:"https://cdn.intechopen.com/books/images_new/9428.jpg",editedByType:null,editors:[{id:"86501",title:"Dr.",name:"Luis",middleName:null,surname:"Romeral Martinez",slug:"luis-romeral-martinez",fullName:"Luis Romeral Martinez"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10107",title:"Artificial Intelligence in Oncology Drug Discovery & Development",subtitle:null,isOpenForSubmission:!0,hash:"043c178c3668865ab7d35dcb2ceea794",slug:null,bookSignature:"Dr. John Cassidy and Dr. Belle Taylor",coverURL:"https://cdn.intechopen.com/books/images_new/10107.jpg",editedByType:null,editors:[{id:"244455",title:"Dr.",name:"John",middleName:null,surname:"Cassidy",slug:"john-cassidy",fullName:"John Cassidy"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10080",title:"Vortex Dynamics",subtitle:null,isOpenForSubmission:!0,hash:"ea97962e99b3e0ebc9b46b48ba5bea14",slug:null,bookSignature:"Dr. Zambri Harun",coverURL:"https://cdn.intechopen.com/books/images_new/10080.jpg",editedByType:null,editors:[{id:"243152",title:"Dr.",name:"Zambri",middleName:null,surname:"Harun",slug:"zambri-harun",fullName:"Zambri Harun"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8903",title:"Carbon Based Material for Environmental Protection and Remediation",subtitle:null,isOpenForSubmission:!0,hash:"19da699b370f320eca63ef2ba02f745d",slug:null,bookSignature:"Dr. Mattia Bartoli and Dr. Marco Frediani",coverURL:"https://cdn.intechopen.com/books/images_new/8903.jpg",editedByType:null,editors:[{id:"188999",title:"Dr.",name:"Mattia",middleName:null,surname:"Bartoli",slug:"mattia-bartoli",fullName:"Mattia Bartoli"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8771",title:"Raman Scattering",subtitle:null,isOpenForSubmission:!0,hash:"1354b3097eaa5b27d9d4bd29d3150b27",slug:null,bookSignature:"Dr. Samir Kumar and Dr. Prabhat Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/8771.jpg",editedByType:null,editors:[{id:"296661",title:"Dr.",name:"Samir",middleName:null,surname:"Kumar",slug:"samir-kumar",fullName:"Samir Kumar"}],productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10073",title:"Recent Advances in Nanophotonics-Fundamentals and Applications",subtitle:null,isOpenForSubmission:!0,hash:"aceca7dfc807140870a89d42c5537d7c",slug:null,bookSignature:"Dr. Mojtaba Kahrizi and Ms. Parsoua Abedini Sohi",coverURL:"https://cdn.intechopen.com/books/images_new/10073.jpg",editedByType:null,editors:[{id:"113045",title:"Dr.",name:"Mojtaba",middleName:null,surname:"Kahrizi",slug:"mojtaba-kahrizi",fullName:"Mojtaba Kahrizi"}],productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:19},humansInSpaceProgram:{},teamHumansInSpaceProgram:{},route:{name:"profile.detail",path:"/profiles/15335/jinglu-tan",hash:"",query:{},params:{id:"15335",slug:"jinglu-tan"},fullPath:"/profiles/15335/jinglu-tan",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()