\r\n\tThis book chapter’s main theme will be focused on transmission dynamics, pathogenesis, mechanisms of host interaction and response, epigenetics and markers, molecular diagnosis, RNA interacting proteins, RNA binding proteins, advanced development of tools for diagnosis, possible development of concepts for vaccines and anti drugs for RNA viruses, immunological mechanisms, treatment, prevention and control. \r\n\t
",isbn:"978-1-80355-667-3",printIsbn:"978-1-80355-666-6",pdfIsbn:"978-1-80355-668-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"52f8a3a1486912beae40b34ac557fed3",bookSignature:"Ph.D. Yogendra Shah",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11369.jpg",keywords:"HIV, Dengue, Zika, West Nile Virus, Chikungunya, Rabies, SARS-CoV2, MERS-CoV, Hanta Virus, Influenza, Whole Genome Sequencing, DNA Sequencing",numberOfDownloads:217,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 4th 2021",dateEndSecondStepPublish:"November 1st 2021",dateEndThirdStepPublish:"December 31st 2021",dateEndFourthStepPublish:"March 21st 2022",dateEndFifthStepPublish:"May 20th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"9 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Shah obtained his Ph.D. degree in Veterinary Medicine from Hokkaido University, Japan. He was awarded the Young Science and Technology Award from the Nepal Academy of Science and Technology (NAST) in 2019. His research interests include infectious diseases, zoonotic infectious diseases, and vector-borne diseases.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah",profilePictureURL:"https://mts.intechopen.com/storage/users/278914/images/system/278914.jpg",biography:"Dr. Yogendra Shah is a consultant microbiologist/virologist, senior research microbiologist, and lecturer at Seti Provincial Hospital, COVID-19 PCR laboratory, National Zoonoses and Food Hygiene Research Center, and Kathmandu College of Science and Technology, Nepal. He obtained a Ph.D. in Veterinary Medicine (Bacteriology) from the Graduate School of Veterinary Medicine, Hokkaido University, Japan, in 2017. His research focuses on better understanding the molecular epidemiological features/transmission dynamics of infectious diseases and zoonotic infectious diseases in Nepal by employing molecular techniques like ELISA, polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and DNA sequencing. He was awarded the Young Science and Technology Award from the Nepal Academy of Science and Technology (NAST) in 2019. His research interests include infectious diseases, zoonotic infectious diseases, and vector-borne diseases. 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\n\t\t\t
1. Introduction
\n\t\t\t
The explosive growth of Internet traffic requires the development of advanced optical telecommunication networks that can enable the high-speed processing of this exponentially growing data traffic. Such advanced network systems will need an enormous number of optical devices, so photonic integrated circuits (PICs) are indispensable for constructing the system at low cost, reduced space, and high reliability. To date, monolithic integration on an indium phosphide (InP) substrate is the most promising way of making PICs because it has the capability to integrate both active and passive optical functions required in optical transport systems for the 1.3-um or 1.55-um telecom window. To develop large-scale, InP-based monolithic PICs, various planar optical devices such as lasers, modulators, detectors, multiplexers/demultiplexers, and optical amplifiers have been developed [1-4].
\n\t\t\t
This paper provides an overview of the present state of research on waveguide optical isolators for InP-based monolithic PICs. Optical isolators are indispensable elements of PICs used to interconnect different optical devices while avoiding the problems caused by undesired reflections of light in the circuit. They must have the form of a planar waveguide because they must be monolithically combined with other semiconductor-waveguide-based optical devices such as lasers, amplifiers, and modulators. Conventional isolators cannot meet this requirement because they use Faraday rotators and polarizers, which are difficult to integrate with waveguide-based semiconductor optical devices. For this reason, many efforts have been expended in developing waveguide isolators [5-11]. Although the research on waveguide isolators is still in the experimental stage, it will probably reach a level of producing practical devices in the near future.
\n\t\t\t
In Section 2, we first give a short sketch of conventional optical isolators. The conventional isolator is a mature device made with established technology and has sufficient performance (low insertion loss and large isolation ratio) for use in optical transport systems. However, it uses bulky components, a Faraday rotator and polarizers, and therefore cannot be used in PICs. We then turn to waveguide optical isolators and, in Section 3, outline two promising methods of making waveguide isolators on InP substrates. All of the methods use semiconductor optical waveguides combined with magnetic materials. One of them is based on the polarization conversion of light caused by the Faraday effect; another is based on a nonreciprocal phase shift in a waveguide interferometer; the third is based on nonreciprocal propagation loss in a magneto-optic waveguide. In the succeeding sections, we focus on the nonreciprocal-loss waveguide isolator and make a detailed explanation of the isolator. In Section 4, we explain the principle and theory of the nonreciprocal-loss phenomenon. Actual devices based on this phenomenon have been developed. In Sections 5, we report the experimental results for the devices consisting of semiconductor optical waveguides combined with manganese arsenide (MnAs), which are ferromagnetic material compatible with semiconductor manufacturing process. We hope that this paper will be helpful to readers who are aiming to develop photonic integrated circuits.
\n\t\t
\n\t\t
\n\t\t\t
2. Conventional optical isolator
\n\t\t\t
Optical isolators are one of the most important passive components in optical communication systems. The function of an optical isolator is to let a light beam pass through in one direction, that is, the forward direction only, like a one-way traffic. Optical isolators are used to prevent destabilizing feedback of light that causes undesirable effects such as frequency instability in laser sources and parasitic oscillation in optical amplifiers.
\n\t\t\t
Ordinary optical isolators available commercially make use of the Faraday effect to produce nonreciprocity. The Faraday effect is a magneto-optic phenomenon in which the polarization plane of light passing through a transparent substance is rotated in the presence of a magnetic field parallel to the direction of light propagation. The Faraday effect occurs in many solids, liquids, and gases. The magnitude of the rotation depends on the strength of the magnetic field and the nature of the transmitting substance. Unlike in the optical activity (or natural activity), the direction of the rotation changes its sign for light propagating in reverse. For example, if a ray traverses the same path twice in opposite directions, the total rotation is double the rotation for a single passage. The Faraday effect is thus non-reciprocal.
\n\t\t\t
Figure 1.
Schematic structure of ordinary optical isolator.
\n\t\t\t
\n\t\t\t\tFigure 1 shows the schematic structure of an ordinary optical isolator. The isolator consists of three components, i.e., a Faraday rotator, an input polarizer, and an output polarizer. The Faraday rotator consists of a magnetic garnet crystal such as yttrium iron garnet and terbium gallium garnet placed in a cylindrical permanent magnet and rotates the polarization of passing light by 45 . As illustrated in Figure 1, light traveling in the forward direction (from A to B) will pass through the input polarizer and become polarized in the vertical plane (indicated by Pi). On passing through the Faraday rotator, the plane of polarization will be rotated 45 on axis. The output polarizer, which is aligned 45 relative to the input polarizer, will then let the light pass through. In contrast, light traveling in the reverse direction (from B to A) will pass through the output polarizer and become polarized by 45 (indicated by Pr). The light will then pass through the Faraday rotator and experience additional 45 of non-reciprocal rotation. The light is now polarized in the horizontal plane and will be rejected by the input polarizer, which allows light polarized in the vertical plane to pass through.
\n\t\t\t
The ordinary optical isolator is bulky (therefore called a bulk isolator) and incompatible with waveguide-based optical devices, so it cannot be used in PICs. It has, however, superior optical characteristics (low forward loss and high backward loss) as shown in Figure 2 [12]. Such good performance is a target in developing waveguide optical isolators.
\n\t\t
\n\t\t
Figure 2.
Optical characteristics of ordinary isolators available commercially. [12]
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\n\t\t\t
3. Recent progress in waveguide optical isolators
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\n\t\t\t\t
3.1. How to make waveguide optical isolators
\n\t\t\t\t
There are several strategies to develop waveguide optical isolators that can be integrated monolithically with waveguide-based semiconductor optical devices on an InP substrate. The strategies can be classified into two types. One is to use the Faraday effect as in conventional bulk isolators. Transferring the principle of bulk isolators to a planer waveguide geometry raises a number of inherent difficulties such as the discoherence of polarization rotation induced by structural birefringence. Therefore new idea is needed to use the Faraday effect in waveguide structure. Sophisticated examples are the Cotton-Mouton isolator [13, 14] and the quasi-phase-matching (QPM) Faraday rotation isolator [15, 16]. The latter in particular have attracted attention in recent years because of its compact techniques for producing the device. The other strategy to make waveguide isolators is to use asymmetric magneto-optic effects that occur in semiconductor waveguides combined with magnetic material. Leading examples are the nonreciprocal-phase-shift isolator [17-20] and the nonreciprocal-loss isolator [21-26]. The nonreciprocal-loss isolator uses no rare-earth garnet, so it is very compatible with standard semiconductor manufacturing processes. In the following sections, we give the outline of the QPM Faraday rotation isolator and the nonreciprocal-phase-shift isolator. The nonreciprocal-loss isolator, which has been developed in our laboratory, is explained in detail in Section 4.
\n\t\t\t\t\tFigure 3 shows a schematic of the QPM Faraday rotation isolator. The device consists of a Faraday rotator (non-reciprocal) section and a polarization rotator (reciprocal) section integrated with a semiconductor laser diode that provides an TE-polarized output. The Faraday rotator section consists of an AlGaAs/GaAs waveguide combined with a sputter-coated film of magnetic rare-earth garnet CeY2Fe5Ox. To obtain an appropriate polarization rotation, this device uses the QPM Faraday effect in an upper-cladding that periodically alternates between magneto-optic (MO) and non-MO media. Incident light of TE mode traveling in the forward direction will first pass through the Faraday rotator section to be rotated by +45 . The light then passes through the reciprocal polarization rotator section and is rotated by -45 . Consequently, the light keeps its TE mode and passes through the output edge. In contrast, backward traveling light of TE mode from the output filter is first rotated by +45 in the reciprocal polarization rotator and then nonreciprocally rotated by +45 in the Faraday rotator section. Consequently, backward light is transformed into a TM mode and therefore has no influence on the stability of the laser because the TE-mode laser diode is insensitive to TM-polarised light. The point of this device is TE-TM mode conversion in the waveguide. At the present time, efficient mode conversion cannot be achieved, so practical devices have yet to be developed.
\n\t\t\t\t
Figure 3.
Schematic of QPM Faraday rotation isolator.
\n\t\t\t\t
Using magneto-optical waveguides made of Cd1-xMnxTe is effective to achieve efficient mode conversion [27, 28]. Diluted magnetic semiconductor Cd1-xMnxTe has the zincblende crystal structure, the same as that of ordinary electro-optical semiconductors such as GaAs and InP. Therefore, a single crystalline Cd1-xMnxTe film can be grown epitaxially on GaAs and InP substrates. In addition, Cd1-xMnxTe exhibits a large Faraday effect near its absorption edge because of the anomalously strong exchange interaction between the sp-band electrons and localized d electrons of Mn2+. Almost complete TE-TM mode conversion (98%+/-2% conversion) was observed in a Cd1-xMnxTe waveguide layer on a GaAs substrate [27, 28].
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3.3. Nonreciprocal phase-shift isolator
\n\t\t\t\t
The nonreciprocal-phase-shift isolator uses a modified Mach-Zehnder interferometer that is designed so that light waves traveling in two arms will be in-phase for forward propagation and out-of-phase for backward propagation. Figure 4 shows the structure of the isolator combined with a laser. The InGaAsP Mach-Zehnder interferometer consists of a pair of three-guide tapered couplers, and an ordinary reciprocal 90 shifter on one of the arms. Reciprocal phase shifting is achieved simply by setting a difference in dimensions or a refractive index between the optical paths along two arms. A magnetic rare-earth garnet YIG:Ce layer is placed on the arms to form a nonreciprocal 90 phase shifter on each arm. The garnet layer was pasted on the interferometer by means of a direct-bonding technique. Two external magnetic fields are applied to the magnetic layer on the two arms in an anti-parallel direction, as shown in Figure 4; this produces a nonreciprocal phase shift in the interferometer in a push-pull manner. The isolator operates as follows. A forward-traveling light wave from the laser enters the central waveguide of the input coupler and divided between the two arms. During the light wave traveling in the arms, a -90 nonreciprocal phase difference is produced, but it is canceled by a +90 reciprocal phase difference. The divided two waves recouple at the output coupler, and output light will appear in the central waveguide. In contrast, for a backward-traveling wave from the output coupler, the nonreciprocal phase difference changes its sign to +90 , and it is added to the reciprocal phase difference to produce a total difference of 180 . Consequently, output light will appear in the two waveguides on both sides of the input coupler and not appear in the central waveguide.
4. Nonreciprocal loss phenomenon in magneto-optic waveguides
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\n\t\t\t\t
4.1. What is nonreciprocal loss phenomenon
\n\t\t\t\t
One of the promising ways of creating waveguide optical isolators is by making use of the phenomenon of nonreciprocal loss. This phenomenon is a nonreciprocal magneto-optic phenomenon where——in an optical waveguide with a magnetized metal layer——the propagation loss of light is larger in backward than in forward propagation. Using this phenomenon can provide new waveguide isolators that use neither Faraday rotator nor polarizer and, therefore, are suitable for monolithic integration with other optical devices on an InP substrate. The theory of the nonreciprocal loss phenomenon was first proposed by Takenaka, Zaets, and others in 1999 [29, 30]. After that, Ghent University-IMEC and Alcatel reported leading experimental results in 2004; they made an isolator consisting of an InGaAlAs/InP semiconductor waveguide combined with a ferromagnetic CoFe layer for use at 1.3-m wavelength [21, 22]. Inspired by this result, aiming to create polarization-insensitive waveguide isolators for 1.5-μm-band optical communication systems, we have been developing both TE-mode and TM-mode isolators based on this phenomenon. We built prototype devices and obtained a nonreciprocity of 14.7 dB/mm for TE-mode devices and 12.0 dB/mm for TM-mode devices——to our knowledge, the largest values ever reported for 1.5-μm-band waveguide isolators. The TE-mode device consisted of an InGaAsP/InP waveguide with a ferromagnetic Fe layer attached on a side of the waveguide [24]. For the TM-mode device, instead of ordinary ferromagnetic metals, we used ferromagnetic intermetallic compounds MnAs and MnSb, which are very compatible with semiconductor manufacturing processes. The following sections provide the details on this TM-mode isolator.
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4.2. Structure of the TM-mode waveguide isolator
\n\t\t\t\t
\n\t\t\t\t\tFigure 5 illustrates our TM-mode waveguide isolators with a cross section perpendicular to the direction of light propagation. Two kinds of structure are shown. The device consists of a magneto-optical planar waveguide that is composed of a TM-mode semiconductor optical-amplifying waveguide (SOA waveguide) on an InP substrate and a ferromagnetic layer attached on a top of the waveguide. To operate the SOA, a metal electrode is put on the surface of the ferromagnetic layer (a driving current for the SOA flows from the electrode to the substrate). Incident light passes through the SOA waveguide perpendicular to the figure (z-direction). To operate the device, an external magnetic field is applied in the x-direction so that the ferromagnetic layer is magnetized perpendicular to the propagation of light. Light traveling along the waveguide interacts with the ferromagnetic layer.
The nonreciprocal propagation loss is caused by the magneto-optic transverse Kerr effect in the magneto-optical planar waveguide. To put it plainly for TM-mode light, the nonreciprocity is produced when light is reflected at the interface between the magnetized ferromagnetic layer and the SOA waveguide. The light reduces its intensity when reflected from the ferromagnetic layer, which absorbs light strongly, and the reduction is larger for backward propagating light than forward propagating light because of the transverse Kerr effect. As a result, the propagation loss is larger for backward propagation (-z-direction) than for forward propagation (z-direction). Figure 6 illustrates the operation of the isolator on the propagation constant plane of the waveguide. The backward light is attenuated more strongly than forward light. Since forward light is also attenuated, the SOA is used to compensate for the forward loss; the SOA is operated so that the net loss for forward propagation will be zero. Under these conditions, the waveguide can act as an optical isolator.
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Figure 6.
Principle of nonreciprocal-loss waveguide isolator.
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4.3. Theory of nonreciprocal loss in the waveguide isolator
\n\t\t\t\t
Let us calculate the nonreciprocal loss in the magneto-optic waveguide and design optimized structure for the isolator device, using electromagnetic simulation. In the TM-mode isolator, light traveling along the SOA waveguide extends through the cladding layer into the ferromagnetic layer to a certain penetration depth and interacts with magnetization vector in the ferromagnetic layer (see Figure 5). Therefore, the thicknesses of the cladding layer and the ferromagnetic layer greatly affect the performance—the isolation ratio and forward loss (insertion loss) —of the isolator as follows:
\n\t\t\t\t
A large isolation ratio can be obtained at small cladding-layer thickness because a thin cladding layer easily lets light through into the ferromagnetic layer to produce a large magneto-optic interaction. Therefore, the cladding layer has to be thin as long as the amplifying gain of the SOA can compensate for the absorption loss of light in the ferromagnetic layer.
The ferromagnetic layer has to be thicker than its penetration depth of light. If it is not, light leaks out of the upper part of the ferromagnetic layer and is needlessly absorbed by the metal electrode. This reduces the isolation ratio because part of the propagating light in the device cannot interact with the ferromagnetic layer.
\n\t\t\t\t
To determine the optimum thicknesses of the cladding and ferromagnetic layers, we calculated the isolation ratio and the insertion loss of the device as a function of the thicknesses by means of two-dimensional electromagnetic simulation based on the finite difference method (FDM).
\n\t\t\t\t
In this device, the structure of the SOA has an influence on the device performance as well. However, the SOA structure cannot be changed greatly under the condition that the SOA should amplify TM-mode light at 1.5-μm-band wavelength. Therefore, we focus only on the thicknesses of the cladding and ferromagnetic layers to optimize the device performance.
\n\t\t\t\t
The nonreciprocity of the device is caused by the off-diagonal elements in the dielectric tensor of the ferromagnetic layer. The dielectric tensor of each layer in the device is given by
where εn is the diagonal element of the tensor in nth layer. The off-diagonal element α is 0 except in the ferromagnetic layer. Using these tensors, we write the Maxwell’s equations in an isotropic charge-free medium as
where we used\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t∇\n\t\t\t\t\t\t\t\t\t×\n\t\t\t\t\t\t\t\t\t(\n\t\t\t\t\t\t\t\t\t∇\n\t\t\t\t\t\t\t\t\t×\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t)\n\t\t\t\t\t\t\t\t\t=\n\t\t\t\t\t\t\t\t\t∇\n\t\t\t\t\t\t\t\t\t(\n\t\t\t\t\t\t\t\t\t∇\n\t\t\t\t\t\t\t\t\t⋅\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t)\n\t\t\t\t\t\t\t\t\t−\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t∇\n\t\t\t\t\t\t\t\t\t\t2\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t, and \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tk\n\t\t\t\t\t\t\t\t\t\t0\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t=\n\t\t\t\t\t\t\t\t\tω\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\tμ\n\t\t\t\t\t\t\t\t\t\t\t\t0\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\tε\n\t\t\t\t\t\t\t\t\t\t\t\t0\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t=\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t2\n\t\t\t\t\t\t\t\t\t\t\tπ\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t/\n\t\t\t\t\t\t\t\t\t\tλ\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t is the free-space propagation constant. Using the second and third equations in (3-2) and\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t∂\n\t\t\t\t\t\t\t\t\t\tz\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t=\n\t\t\t\t\t\t\t\t\tj\n\t\t\t\t\t\t\t\t\tβ\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t, the z component of eq. (3-3) can be written as
where β is the propagation constant in the device along z direction, Et\n\t\t\t\t\t and Ht\n\t\t\t\t\t (t = x, y, z) are electric field (parallel to t axis) and magnetic field (parallel to t axis) of the light.
\n\t\t\t\t
The y and z components of the first equation in (3-2) can be given by the equations for TM-mode light (Ex\n\t\t\t\t\t = Hy\n\t\t\t\t\t = Hz\n\t\t\t\t\t = 0),
From eqs. (3-6) and (3-7), we can obtain the scalar wave equation for magnetic field Hx\n\t\t\t\t\t of TM waves in each layer. The wave equation in non-magnetic layers (α=0) is given by
For the ferromagnetic layer, the wave equation has first-order and third-order derivative terms because of the nonzero off-diagonal element α in the dielectric tensor. For ordinary values of α in ferromagnetic materials, third-order terms of \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t∂\n\t\t\t\t\t\t\t\t\t\tx\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t2\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t∂\n\t\t\t\t\t\t\t\t\t\ty\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\t\t\t\tx\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t and \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t∂\n\t\t\t\t\t\t\t\t\t\ty\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t3\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\t\t\t\tx\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t are small and can be ignored. In consequence, the wave equation in the ferromagnetic layer is given by
Because of the nonzero off-diagonal elements in the dielectric tensor, the equation involves a linear term in the propagation constant β; this leads to a nonreciprocal solution to the propagation direction. The nonreciprocal solution gives a difference in absorption coefficient between forward (z-direction) and backward (-z-direction) TM waves and, therefore, gives the isolation ratio (or the difference between forward absorption and backward absorption) in the device.
\n\t\t\t\t
To solve the wave equation numerically, we partition the domain in space using a mesh x\n\t\t\t\t\t0, x\n\t\t\t\t\t1,…xp\n\t\t\t\t\t,… in x direction and mesh y\n\t\t\t\t\t0, y\n\t\t\t\t\t1,…yq\n\t\t\t\t\t,… in y direction with a mesh width (the difference between two adjacent space points) of m in x direction and n in y direction. We represent the magnetic field on each mesh point (xp\n\t\t\t\t\t, yq\n\t\t\t\t\t) by Hp,q\n\t\t\t\t\t. Using a second-order central difference for the space derivative at position (xp\n\t\t\t\t\t, yq\n\t\t\t\t\t), we obtain the recurrence equation
for eq. (3-9). Solving eqs. (3-10) and (3-11) numerically, we can calculate the forward and backward propagation loss and the isolation ratio, as a function of the thicknesses of the cladding layer and the ferromagnetic layer, where the SOA is not operated. (In actual operation, the SOA is operated so that it compensates for the forward propagation loss.)
\n\t\t\t\t
Before calculating the optimum thicknesses of the cladding and ferromagnetic layers, we must design the appropriate structure of the SOA region to amplify 1.5-μm TM-mode light. The structural parameters we used for the SOA was as follows. The substrate is a highly doped n-type InP (refractive index n = 3.16). The constituent layers of the SOA are: (i) lower guiding layer: 100-nm thick InGaAlAs (bandgap wavelength λg\n\t\t\t\t\t = 1.1 μm, n = 3.4), (ii) MQW: five InGaAs quantum wells (-0.4% tensile-strained, 15-nm-thick well, nMQW\n\t\t\t\t\t = 3.53) with six InGaAlAs barriers (+0.6% compressively strained, 12-nm-thick barrier, λg\n\t\t\t\t\t = 1.2 μm), and (iii) upper guiding layer: 100-nm-thick InGaAlAs (λg\n\t\t\t\t\t = 1.1 μm, n = 3.4).
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Figure 7.
a) Forward absorption loss (propagation loss) and (b) isolation ratio (nonreciprocity) in the device as a function of Ferromagnetic-layer thickness and cladding layer thickness, calculated for 1.55-μm TM mode.
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For the isolator with this SOA region, we calculated the propagation loss and the isolation ratio, using the method described above. Figure 7 shows an example of the results, i.e., (a) the absorption loss for forward propagation and (b) the isolation ratio as a function of the InP-cladding and ferromagnetic layer thicknesses. In this simulation, we assumed a device consisting of a ridge-shaped optical amplifying waveguide (see Figure 5(b)) covered with a ferromagnetic MnAs layer and an Au-Ti metal electrode. The reason we used manganese pnictides as the ferromagnetic layer will be explained in Section 5. The parameters we used in the simulation are given in Table 1. The forward absorption loss in the device is large and the isolation ratio is small at small MnAs thickness because part of the propagating light in the device leaks out of the MnAs layer and is needlessly absorbed by the Au-Ti electrode. As MnAs layer thickness increases, forward absorption loss decreases and isolation ratio increases, both approaching a constant in MnAs layers thicker than 200 nm. This means that light penetrates to a depth of about 200 nm in the MnAs layer. Therefore, more than 200 nm can be considered a necessary and sufficient thickness for the MnAs layer when fabricating devices.
\n\t\t\t\t
\n\t\t\t\t\tFigure 7 also shows that both the isolation ratio and the absorption loss increase as the thickness of the InP-cladding layer decreases. This is so because a thinner cladding layer lets a higher percentage of light through into the MnAs layer, producing a larger interaction. A thin cladding layer is preferable for obtaining a large isolation ratio as long as the forward absorption loss can be compensated for by the amplifying gain of the SOA. We expected an SOA gain of 16 dB/mm, and therefore decided that the optimum thickness of the cladding layer was 350 nm.
\n\t\t\t\t
\n\t\t\t\t\tFigure 8 illustrates the distribution profile of light traveling in the isolator for forward and backward propagation, with the results calculated for a device with a 350-nm InP-cladding layer and a 200-nm MnAs layer. Figure 8(a-1) and 8(b-1) show the contour lines for TM magnetic field vector intensity—large magnetic fields in the central part—on the cross
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Table 1.
Example of parameters used for calculating device characteristics.
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Figure 8.
Distribution profile of light traveling in isolator, calculated for 1.55 μm TM mode, with a 350-nm cladding layer and a 200-nm MnAs layer: cross section of distribution for (a-1) forward and (b-1) backward propagating light; distribution along vertical center line (dashed lines in (a-1) and (b-1)) of device for (a-2) forward and (b-2) backward propagating light.
\n\t\t\t\t
section (x-y plane) of the device, where Figure 8(a-1) is for forward propagating light and Figure 8(b-1) is for backward light. Figure 8(a-2) and 8(b-2) depict the magnetic field vector intensity along the vertical center line (dashed lines in Figure 8(a-1) and 8(b-1)) of the device, where Figure 8(a-2) is for forward light and Figure 8(a-2) is for backward light. Unlike forward propagating light, backward propagating light shifts its distribution tail to the MnAs layer and, therefore, suffers a larger absorption loss in the MnAs layer. Therefore, the propagation loss of light is larger in backward than in forward propagation.
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5. Prototype device with ferromagnetic MnAs
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5.1. Using manganese pnictides as a ferromagnetic material
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The point of our device is its use of manganese arsenide (MnAs) as a ferromagnetic material, instead of ordinary ferromagnetic metals such as Fe and Co. In our device structure——which is necessary for TM-mode operation——the ferromagnetic layer used to produce the nonreciprocity is also used as a contact to supply a driving current to the SOA. This means that the ferromagnetic layer has to meet a dual requirement of (i) producing a large Kerr effect at the wavelength of 1.5 μm and of (ii) providing a low-barrier contact for p-type III-V semiconductors. Ordinary ferromagnetic metals are not suited for this purpose because they produce a Schottky barrier on III-V semiconductors, thereby producing a high-resistance contact on the contact layer. In addition, during contact annealing, they produce undesirable nonferromagnetic compounds such as FeAs and CoAs at the contact interface and simultaneously degrade the microscopic flatness of the interface; this reduces optical nonreciprocity in the device. To solve these problems, we used manganese arsenide, MnAs, for the ferromagnetic layer. MnAs are ferromagnetic, intermetallic compounds with a NiAs-type hexagonal structure (see Figure 9). They can be grown epitaxially on GaAs, InP, and related semiconductors by means of molecular beam epitaxy (MBE), without producing a solid-phase reaction at the interface [31-34]. MnAs is suitable ferromagnetic materials for our device because they have enough Kerr effect at 1.5-μm wavelength to produce practical nonreciprocity and, at the same time, can make a low-resistance contact on III-V semiconductors. The Currie temperature is 40C for MnAs.
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Figure 9.
Structure of manganese pnictides.
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To take the first step, we made a device with a MnAs layer because the epitaxial growth technology of MnAs layers on III-V semiconductors was well established [31-33]. To reduce the propagation loss of light and obtain a single-mode operation, we used the ridge waveguide structure with a large lateral-confinement factor (see Figure 5(b)). In the following sections, we provide details of the fabrication process and operation characteristics of the device that uses ferromagnetic MnAs.
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5.2. Constructing the device
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\n\t\t\t\t\tFigure 10(a) is a cross-sectional diagram of our TM-mode waveguide isolator with a ferromagnetic MnAs layer. The MnAs layer covers the SOA surface, and two interface layers (a highly doped p-type InGaAs contact layer and a p-type InP cladding layer) are inserted between the two. The InGaAs contact layer has to be thin so that 1.5-μm light traveling in the SOA will extend into the MnAs layer (the absorption edge of the contact layer is about 1550 nm). An Au/Ti double metal layer covers the MnAs layer, forming an electrode for current injection into the SOA. Light passes through the SOA waveguide in a direction perpendicular to the figure (z direction). An Al2O3 insulating layer separates the SOA surface from the Au-Ti electrode except on the contact region. Incident light passes through the SOA waveguide perpendicular to the figure (z direction).
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Figure 10.
a) Schematic cross section of our waveguide isolator for 1.5-μm TM mode, consisting of a ridge-shaped optical amplifying waveguide covered with a MnAs layer magnetized in x-direction. Light propagates along z-direction. (b) SEM cross section of device.
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On the basis of the simulation results mentioned in Section 4.3, we fabricated a device as follows. The substrate was a highly doped, [100]-oriented n-type wafer of InP. The SOA was formed on the substrate by metalorganic vapor-phase epitaxy (MOVPE). The MQW showed a photoluminescence peak at 1.54 μm——this means that the SOA had a gain peak at 1.54 μm. The thicknesses of the p-InP cladding and p+InGaAs contact layers were set to be 350 nm and 10nm. After the formation of the SOA, a 200 nm MnAs layer was grown on the surface of the p+InGaAs contact layer by MBE. The wafer was first heat treated at about 550 oC under As2 flux in the MBE chamber to remove a native oxide layer on the contact layer. The wafer temperature was then lowered to 200oC, and the As2 flux was kept supplying to form an As template on the surface. This As template on the surface is important to grow high quality MnAs, as in the growth of MnAs layers on GaAs [31, 32] and InP [33]. The surface of the InGaAs contact layer with the As template showed spotty refraction high energy electron diffraction (RHEED) pattern. After that, Mn and As2 fluxes were supplied on the surface to grow a 200 nm MnAs thin film. During the growth process, we confirmed (1×2) reconstruction in RHEED, indicating that the MnAs structural properties were improved. An X-ray diffraction pattern showed strong MnAs peaks in [1-100] directions.
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After the growth of MnAs, the ridge waveguide structure was formed as follows. First, a photoresist mask in the form of a 2-μm-wide waveguide pattern was made on the surface of the MnAs layer. Then, the MnAs layer, InP cladding layer, and InGaAs contact layers were selectively etched in this order to fabricate a ridge waveguide—the MnAs layer was etched by reactive ion etching with Ar, and the cladding and the contact layers were wet-etched with a Br2-HBr-H2O solution. An Al2O3 layer was deposited on this ridge waveguide using electron-beam (EB) evaporation. Then, the Al2O3 on the contact layer was removed using a lift-off process. Finally, a Ti layer and an Au layer were deposited to make a top electrode, using EB evaporation. This was the process we used to fabricate the structure depicted in Figure 10(a). Finally, both ends of the device were cleaved, and the cleaved surfaces were left uncoated. Figure 10(b) is a cross section of the device as observed with scanning electron microscopy (SEM).
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Figure 11.
Magnetization curve for MnAs layer, measured with a AGFM. MnAs layer can be easily magnetized along [011] direction of InP substrate. In contrast, magnetization is difficult along [01-1] direction.
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MnAs thin films grown on the InGaAs contact layer showed strong magnetocrystalline anisotropy——an intrinsic property of a ferrimagnet, independent of grain size and shape; the MnAs thin films were easily magnetized along the [011] direction of the InP substrates. Based on the fact, we formed the waveguide stripe parallel to the [0-11] direction of the InP substrate, and applied an external magnetic field to the [011] direction (x-direction in Figure 10). However, in addition to the magnetocrystalline anisotropy, the shape anisotropy of the MnAs layer must be taken into consideration for the fabricated device because our device (or the MnAs layer) had the form of the 2-μm-wide waveguide structure. Therefore, we confirmed a magnetization curve of the MnAs layer in our device before measuring device characteristics. Figure 11 shows a plot of the magnetization curve, measured by alternating gradient force magnetometry (AGFM). Along the [011] direction of the InP substrate, the MnAs layer showed a soft hysteresis curve and was easily magnetized with a small coercive field of 0.07 T. In contrast, the magnetization was not easy along the [01-1] direction and was insufficient even in a magnetic field of 0.5 T. This means that the magnetocrystalline anisotropy is larger than the shape anisotropy in our device, and the device was expected to work with an external magnetic field of 0.07-0.1 T (initial magnetizing requires 0.15-0.2 T).
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5.3. Device operation
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We confirmed that the device functioned successfully as an optical isolator with nonreciprocal loss for TM-polarized, 1.5-μm light. Figure 12 shows our experimental setup for the measurement. It consisted of a wavelength-tunable laser, two polarization controllers, two circulators, two optical switches, an output coupler, an optical power meter, and an optical spectrum analyzer (OSA). Light from a tunable laser was transmitted to the device through a polarization controller and a circulator. The light was transferred into and out of the device using lensed-fiber couplers. A magnetic field was applied using a permanent magnet along the [011] direction of the device, i.e., parallel to the surface of the device and perpendicular to the direction of light propagation. Light propagation in the device was switched between forward direction (switch node 1–upper circulator–device–lower isolator– switch node 4 in Figure 12) and backward direction (node 2–lower circulator–
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Figure 12.
Experimental setup for measuring isolation ratio and propagation loss of light in device.
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device–upper isolator–node 3) by controlling the optical switches. The intensity of light transmitted in the device (or the output light from the device) was measured using the optical spectrum analyzer and the power meter. The output of the tunable laser was set to 5 dBm, and the magnetic field for the device was set to 0.1 T. During measurement, the device was kept at 20oC and operated with a SOA driving current of 100 mA. The MnAs layer successfully provided a low-resistance contact for the InGaAs contact layer. The voltage drop across the device 0.65 mm in length was only 1.7 V (SOA diode drop 0.9 V plus ohmic contact drop 0.8 V), whereas the drop across a control device with Fe-Ni layers instead of MnAs was 3.0 V (SOA diode drop 0.9 V plus ohmic contact drop 2.1 V) [35].
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\n\t\t\t\t\tFigure 13 shows the transmission spectra of the device with a length of 0.65 mm. The intensity of the output light from the device is plotted as a function of wavelength for forward (dashed line) and backward (solid line) propagation of (a) TM-polarized and (b) TE-polarized light. The wavelength of incident light was fixed at 1.54 μm, which was the gain peak wavelength of the SOA. For TM-mode light, the output intensity changed by 4.7 dB by switching the direction of light propagation. The device operated efficiently as a TM-mode isolator with an isolation ratio of 7.2 dB/mm (= 4.7 dB/0.65 mm). In contrast, the output intensity for TE-mode light was not dependent on the direction of the light propagation. Small periodic ripples in amplified spontaneous emission spectra are shown in Figure 13. They are caused by Fabry-Perot interference due to reflection from cleaved facets; the period was consistent with the value predicted from the length and effective refractive index of the device. The inset in Figure 13(a) is the near-field pattern of the TM-mode forward propagating light and shows that the device operated successfully in a single mode.
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Figure 13.
Transmission spectra of device for forward transmission (dashed line) and backward transmission (solid line), measured for (a) TM-mode and (b) TE-mode, at 1.54-μm wavelength, 100-mA driving current, and 0.1-T magnetic field. Device is 0.65 mm long. Data on transmission intensity include loss caused by measurement system. Inset is near-field pattern of TM-mode forward propagating light.
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The data of transmission intensity in Figure 13 include the loss caused by the measurement system. To examine the intrinsic transmission loss of the device, we measured the transmission intensity for devices with different lengths. Figure 14 shows the results, i.e., the output intensity for forward and backward transmission as a function of device length (isolation ratio is also plotted). The slope of the forward line gives the intrinsic transmission loss (or absorption loss) per unit length. We estimated that forward loss in the device was 10.6 dB/mm—still large for practical use. This is so because the gain of the SOA was lower than we had expected, and therefore, insufficient to compensate for the intrinsic transmission loss in the device. The loss caused by the measurement system can also be calculated using the vertical-axis intercept of the forward line and the output intensity of the tunable laser. It was estimated to be 28 dB—output coupler loss 3 dB plus lensed-fiber coupling loss 12.5 dB/facet × 2 between the measurement system and the device.
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Figure 14.
Transmission intensity as a function of device length, measured for 1.54 μm TM mode, with 100-mA driving current and 0.1-T magnetic field. Isolation ratio is also plotted.
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\n\t\t\t\t\tFigure 15 is a plot of the isolation ratio, as a function of wavelength from 1.53 to 1.55 μm. The device was 0.65-mm long. The output intensities for forward and backward propagations are also plotted (including the measurement system loss). In this range of wavelength, the isolation ratio was almost constant. The isolation ratio 7.2 dB/mm of this waveguide isolator was still small for practical use. In addition, the device was unable to operate at temperatures higher than room temperature because the Currie temperature of MnAs is only 40C. To improve the device performance, we have to seek other superior ferromagnetic materials. In the next section, we present a device that uses MnSb instead of MnAs.
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Figure 15.
Isolation ratio as a function of a wavelength from 1.53 to 1.55 μm for a 0.65-mm long device. Transmission intensity is also plotted for forward and backward propagation (including measurement system loss).
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6. Conclusion
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An important element for developing photonic integrated circuits is waveguide optical isolators that can be monolithically combined with other waveguide-based devices such as lasers. One promising way of creating such waveguide isolators is by using the phenomenon of nonreciprocal loss in magneto-optical waveguides. Making use of this phenomenon, we have been developing TE- and TM-mode waveguide isolators operating at 1.5-m telecommunication band. As a fromagnetic material for the magneto-optical waveguide isolator, manganese pnictides such as MnAs are more superior than ordinary ferromagnetic metals because they can be formed on GaAs, InP, and related materials using semiconductors manufacturing process. Although MnAs is not common material at present for integrated optics, it will soon bring technical innovation in functional magneto-optic devices for large-scale photonic integrated circuits.
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\n\t\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/6776.pdf",chapterXML:"https://mts.intechopen.com/source/xml/6776.xml",downloadPdfUrl:"/chapter/pdf-download/6776",previewPdfUrl:"/chapter/pdf-preview/6776",totalDownloads:2869,totalViews:167,totalCrossrefCites:0,totalDimensionsCites:1,totalAltmetricsMentions:0,introChapter:null,impactScore:0,impactScorePercentile:16,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:null,dateReviewed:null,datePrePublished:null,datePublished:"January 1st 2010",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/6776",risUrl:"/chapter/ris/6776",book:{id:"3582",slug:"advances-in-optical-and-photonic-devices"},signatures:"T. Amemiya and Y. Nakano",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Conventional optical isolator",level:"1"},{id:"sec_3",title:"3. Recent progress in waveguide optical isolators",level:"1"},{id:"sec_3_2",title:"3.1. How to make waveguide optical isolators",level:"2"},{id:"sec_4_2",title:"3.2. Quasi-phase-matching faraday rotation isolator",level:"2"},{id:"sec_5_2",title:"3.3. Nonreciprocal phase-shift isolator",level:"2"},{id:"sec_7",title:"4. Nonreciprocal loss phenomenon in magneto-optic waveguides",level:"1"},{id:"sec_7_2",title:"4.1. What is nonreciprocal loss phenomenon",level:"2"},{id:"sec_8_2",title:"4.2. Structure of the TM-mode waveguide isolator",level:"2"},{id:"sec_9_2",title:"4.3. Theory of nonreciprocal loss in the waveguide isolator",level:"2"},{id:"sec_11",title:"5. Prototype device with ferromagnetic MnAs",level:"1"},{id:"sec_11_2",title:"5.1. Using manganese pnictides as a ferromagnetic material",level:"2"},{id:"sec_12_2",title:"5.2. Constructing the device",level:"2"},{id:"sec_13_2",title:"5.3. Device operation",level:"2"},{id:"sec_15",title:"6. 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C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAndo\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 ApplPhys.Lett84\n\t\t\t\t\t565\n\t\t\t\t\t567 .\n\t\t\t'},{id:"B28",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakenaka\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakano\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999Procof. I. E. E. E.Conferenceon.IndiumPhosphide.RelatedMaterials. 289\n\t\t\t\t\t292 .\n\t\t\t'},{id:"B29",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZaets\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAndo\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999 PhotonicsI. E. E. E.TechnolLett.11\n\t\t\t\t\t1012\n\t\t\t\t\t1014 .\n\t\t\t'},{id:"B30",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTanaka\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarbison\n\t\t\t\t\t\t\tJ. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRothberg\n\t\t\t\t\t\t\tG. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994ApplPhys.Lett 65\n\t\t\t\t\t1964\n\t\t\t\t\t1966 .\n\t\t\t'},{id:"B31",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDaweritz\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWan\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJenichen\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHerrmann\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMohanty\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTrampert\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPloog\n\t\t\t\t\t\t\tK. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 ApplJ.Phys96\n\t\t\t\t\t5052\n\t\t\t\t\t5056 .\n\t\t\t'},{id:"B32",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYokoyama\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhya\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTanaka\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 ApplPhys.Lett 88, 012504.\n\t\t\t'},{id:"B33",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAkinaga\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTanaka\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAndo\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKatayama\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCryst\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995Growth 150\n\t\t\t\t\t1144\n\t\t\t\t\t1149 .\n\t\t\t'},{id:"B34",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAmemiya\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShimizu\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakano\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Procof. I. E. E. E.Conferenceon.IndiumPhosphide.RelatedMaterials.303\n\t\t\t\t\t306 .\n\t\t\t'},{id:"B35",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOgawaa\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAmemiya\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShimizu\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakano\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMunekata\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007Proc of International Symposium on Compound Semiconductors TuC-22\n\t\t\t\t\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"T. Amemiya",address:"",affiliation:'
Quantum Nanoelectronics Research Center, Tokyo Institute of Technology, Japan
Research Center for Advanced Science and Technology, University of Tokyo, Japan
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1. Introduction
Macrophages and dendritic cells are key players in activation of the innate and adaptive immune systems. In viral infections, such as HIV-1 and COVID-19, macrophages assume either a more protective or a pathogenic role depending on their classification.
Macrophages are polarized by cytokine signaling from CD4 T cells into the M1 or the M2 type. M1 macrophages are classically activated by interferon-γ (INF-γ), whereas M2 macrophages are activated by interleukin-4 (IL-4) and IL-13 [1]. M1 macrophages have a role in combating infection, whereas M2 macrophages in supporting homeostasis. This inflammatory response, while beneficial against microbes and aggregated molecules, when hyper-activated can lead to tissue damage in the lungs, heart, and brain.
Under conditions of high microbial activity, M1 promote inflammation, synthesize nitric oxide, and induce cytokine production IL-6, IL-12 and tumor necrosis factor (TNF). Type M2 macrophages secrete arginase-I, IL-10 and TGF-β and other anti-inflammatory cytokines promoting wound healing but also contributing to tumor growth. M1 macrophages phagocytize microbes and initiate an adaptive immune response by T cells while M2 macrophages induce collagen repair to maintain tissue repair [1].
The roles of M1 macrophages in opposing the disease and the M2 macrophages in promoting homeostasis, while evident in infectious diseases, is less evident in neurodegenerative diseases. Macrophages of AD patients were classified according to the ratio of cluster of differentiation (CD) surface markers: CD54+ CD80/CD163+ CD206 [2] as follows: the inflammatory M1 macrophage type has the ratio > 4, the anti-inflammatory M2 type has a ratio < 1. Both M1 and M2 are associated with progression of dementia. In AD patients, however, the intermediate M1M2 phenotype with a ratio between 1 and 4 is a pro-resolution type promoting homeostasis and protection against dementia. Infection or other stress can cause an imbalance in the expression of these two macrophage types, as seen by others [3].
Macrophages were first appreciated in tuberculosis, where the dual role of macrophages in containing vs. replicating Mycobacterium tuberculosis (Mtb) has been known for a century. A successful response to mycobacterial infection is a granuloma consisting of lymphocytes, macrophages, Langhans giant cells (fused macrophages around mycobacteria) and fibroblasts [4].
In recent years, the role of macrophages in neurodegenerative diseases, Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), has been appreciated as a result of immunochemical demonstration of central nervous system (CNS) invasion by peripheral blood monocyte/macrophages (MM) in AD patients [5]. Macrophage targets in AD are amyloid-beta (Aβ) and P-tau, while in ALS macrophage targets are aggregated superoxide dismutase (SOD-1) and microbial nucleic acids. Autologous DNA released into the cytoplasm could be a target in the cGAS-STING pathway [6].
This chapter will discuss the integral role and modulation of macrophage role in the therapy of neurodegenerative and infectious diseases. The natural substances polyunsaturated fatty acids (PUFA), circuminoids, vitamin D, and polyphenols improve macrophage transcriptome and functions for brain clearance in neurological diseases, but their mechanisms depend on many variables that are under study. The effects of natural substances on macrophage transcriptome and clearance of Aβ and P-tau could potentiate therapeutic outcome of monocl0nal antibodies, which increase phagocytosis but not degradation or export of Aβ and P-tau.
2. Macrophages of Alzheimer’s disease patients fail in clearance of the AD brain
In AD patients, microglia are the first responders to accumulation of Aβ in the brain, which attract monocyte/macrophages (MM) from the blood into the CNS by chemokines, in particular CCL5 (RANTES) [7]. In non-demented individuals, post-mortem immunochemistry and results from a blood-brain barrier (BBB) model suggest that MM migrate across BBB in both directions, clear Aβ in plaques, degrade or export Aβ from the brain without disruption of BBB or accumulation of macrophages around vessels [5, 8], and deposit Aβ into cervical nodes or further downstream [9]. MM of healthy subjects with the pro-resolution M1M2 phenotype effectively upload Aβ into endosomes, fuse endosomes with lysosomes, and degrade Aβ by lysosomal enzymes. MM of AD patients are defective in internalization and degradation of Aβ in endosomes [8].
In the AD brain, MM immigrate into CNS through disrupted tight junctions between endothelial cells. In addition, opening of tight junctions in the blood-brain barrier (BBB) permits brain entry of fibrin and components of the complement. In the brain parenchyma, AD macrophages invade the plaques but upload Aβ only on its cell surface, do not transport Aβ into endosomes and fail to degrade Aβ. Clearance of individual Aβ plaques by macrophages is functionally stochastic, thus some plaques are not fully cleared [5]. After uploading Aβ, MM migrate to vessels but fail to emigrate across BBB, suffer apoptosis and release Aβ into vessels, which develop cerebro-vascular angiopathy (CAA) (Figure 1) [10].
Figure 1.
Macrophage pathway in the AD brain. Created with BioRender.com.
2.1 Natural substances have mixed results in prevention of Alzheimer’s disease
Natural substances, prominently PUFA, have a long history in prevention of AD in the patients with mild cognitive impairment (MCI). PUFA supplementation had positive cognitive effects in MCI patients, but only in those with very mild MCI [11]. A large controlled clinical trial of PUFA supplementation, however, did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease [12].
Nevertheless, proven effects of PUFA on macrophage transcriptome and functions designate PUFA for immunotherapeutic studies controlled for baseline immune phenotype, APO E genotype, stage of disease, diet and lifestyle using a high-quality omega-fatty acid preparation protected against oxidation [2]. In an uncontrolled study of mild cognitive impairment (MCI) patients supplemented by the omega-3 fatty acid drink Smartfish, macrophage phenotype changed from either a highly inflammatory M1 or a very low non-inflammatory M2 to the desired pro-resolution M1/M2 (Table 1) [2]. Importantly, in this study, PUFA supplementation improved the cognitive status of MCI/AD patients for 4–17 months and protected against dementia for 4.5 years in certain patients [13]. In vivo supplementation and in vitro stimulation by the Smartfish drink stimulated the pro-resolution M1/M2 macrophage type with increased phagocytosis and energy [14].
AD patients
PUFA-supplemented AD patients
M1-type macrophages
↑
↓
M2-type macrophages
Variable
↑
M1/M2 pro-resolution-type macrophages
↓
↑↑
MGAT3 transcription
↓
↑↑
Inflammation
↑↑
↓
Aβ phagocytosis by macrophages
↓
↑
Table 1.
The effects of PUFA-supplementation on Alzheimer’s disease (AD) patients.
A clinical study of supplementation with a high dose of vitamin B complex, including vitamins B6 (pyridoxine), B9 (folic acid), and B12 (cobalamin), showed a reduction in the rate of brain atrophy in MCI patients with elevated total homocysteine [15].
2.2 Alzheimer’s disease patients’ macrophages have transcriptomic defects that underlie their defective function
AD brain cells and macrophages lack energy due to oxidative damage and nitrosylation by reactive oxygen species (ROS) of the glycolytic enzyme transcripts GAPDH, PKM1, and PDH, and the citric acid cycle enzymes ACO2 and OGDH [16]. The defects in macrophage transcriptome in protein-coding and regulatory sequences for energy, glycosylation, unfolded protein response, glymphatic system, Toll-like receptors, and other genes lead to macrophage malfunction and apoptosis [14]. Macrophages exhibit a faulty unfolded protein response (UPR) to endoplasmic reticulum (ER) stress from Aβ phagocytosis. These defects lead to macrophage apoptosis and inflammation [14].
2.3 Natural substances have positive effects on macrophage biochemistry
The anti-inflammatory molecule bisdemethoxycurcumin up regulated MGAT3 transcripts and increased macrophage phagocytosis of Aβ. 1,25 dihydroxy vitamin D3 potentiated the 4,4-diisothiocyanostilbene-2,2-disulfonic acid-sensitive chloride channel ClC-3 currents essential for Aβ phagocytosis [17]. A clinical study of supplementation with a high dose of vitamin B complex, including vitamins B6 (pyridoxine), B9 (folic acid), and B12 (cobalamin), showed a reduction in the rate of brain atrophy in MCI patients with elevated total homocysteine [15].
RNA-seq analysis of single blood cell types in PUFA-supplemented MCI patients showed up-regulation of the transcripts for glycolysis, tricarboxylic acid cycle, OX-PHOS, nicotinamide dinucleotide (NAD+) synthesis in monocytes, neutrophils, regulatory T cells, memory CD4 and CD8 T cells, and NK cells, but the most consistent effects across the whole spectrum were in monocytes/macrophages (MM). Importantly, the supplementation showed that PUFA provide energy for immune clearance of the brain throughout the diurnal cycle and even in hypo- or hyper-glycemia [13]. Both hypo- and hyper-glycemic glucose concentrations in the medium of macrophages in vitro inhibit Aβ phagocytosis, but phagocytosis is restored in presence of PUFA in the medium. Diabetic patients have an increased risk of AD and may benefit from PUFA supplementation to provide missing energy in hypoglycemia and to enhance correct glycation and protect against glucose adducts in hyperglycemia of mild cognitive impairment (MCI) patients.
2.4 Monoclonal antibodies and PUFA in therapy of AD
The approval of aducanumab in 2021 increased enthusiasm for immune therapy by monoclonal antibodies. Aducanumab cleared both soluble oligomers and aggregated Aβ in a dose- and time-dependent fashion according to amyloid positron emission tomography (PET) imaging and slowed disease progression [18]. Both aducanumab and another monoclonal antibody ponezumab, however, have been associated with cerebro-vascular amyloid angiopathy (CAA) in models and with amyloid-related imaging abnormalities (ARIA) in patients [19]. Although the exact mechanisms of CAA related to aducanumab are not known due to the lack of pathological and biochemical studies, this complication appears to be due to macrophage shuttling Aβ from plaques to vessels, failure of macrophages in Aβ degradation and macrophage apoptosis with a release of Aβ into CAA vessels [10]. As PUFA up regulate the transcription of Aβ degradation enzymes, PUFA supplementation could be synergistic with the monoclonal antibody therapy.
3. Macrophages in amyotrophic lateral sclerosis
In amyotrophic lateral sclerosis (ALS), macrophages target aggregated superoxide dismutase (SOD-1) [20] and may be targeting free autologous DNA in the cytoplasm.
Immunopathological studies of sporadic amyotrophic lateral sclerosis (sALS) patients demonstrated an inflammatory attack by macrophages, cytotoxic T cells, NK and mast cells on motor neurons in the spinal cord [21, 22]. The attack includes gray matter and white matter of the spinal cord as well as peripheral nerves. The invading macrophages are inflammatory expressing cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), IL-6 and TNF-α, and they attack both caspase-positive and caspase-negative neurons. In addition, cytotoxic CD8 T cells and NK cells participate in the autoimmune attack expressing the cytotoxic enzymes granzymes.
Aggregated superoxide dismutase-1 (SOD-1) stimulates peripheral blood mononuclear cells (PBMC) of sALS patients inducing IL-1, IL6, and IL23. These cytokines enhance production of the auto-immune pro-inflammatory cytokine IL-17A, which is increased in the serum and spinal cord of ALS patients [23]. The induction of inflammatory pathology in sALS by SOD-1 in aggregated form is an example that in neurodegenerative diseases the aggregated state of the putative culprits SOD-1 in ALS and amyloid-β and P-tau in Alzheimer’s disease is sufficient for induction of inflammatory neuropathology.
4. Macrophages in HIV-1 infection
Trojan transport is the main path for virus penetration the blood-brain barrier in HIV-1 encephalitis. In addition, HIV-1 penetrates across coronary endothelia by transcytosis or by a paracellular route through disrupted tight junction protein ZO-1 [24].
Infiltration of target organs by inflammatory macrophages has a critical role in the progression of HIV-1 encephalitis and HIV-1 myocarditis. Other target organs in AIDS, the liver and the kidneys, are also infiltrated by macr0phages. In patients with HIV-1 encephalitis, cognitive impairment is proportionate to the number of macrophages infiltrating the brain [25]. In a study of postmortem heart tissues from 15 AIDS patients, the failing hearts showed significantly higher infiltration in the left ventricular myocardium by COX-2-positive and iNOS-positive macrophages compared to the functioning hearts. In the hearts with HIV-1 myocarditis, productive infection was exclusively in infiltrating macrophages and T cells, not in cardiomyocytes [26]. Significant infiltration of the failing heart by COX-2-positive macrophages (demonstrated using an antigen-retrieval technique) and production of inflammatory cytokines and mediators, such as NO, quinolinic acid, free radicals, is considered as the main mechanism of heart failure in HIV-1 myocarditis [26].
5. Macrophages in patients with COVID-19 infections
The recent epidemic of SARS-CoV-2 viral infection is associated with severe complications in subjects with risk factors, including older age, obesity, diabetes, renal failure; cancer; chronic obstructive pulmonary disease from smoking; and immunosuppressive conditions. In contrast, SARS-CoV-2 infected subjects without risk factors may suffer only mild pulmonary damage [27].
SARS-CoV-2 and previous coronaviruses responsible for severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) induce inflammatory activation of monocytes/macrophages (MM). Patients with a low expression of interferon–α/β/γ in macrophages may suffer severe pulmonary damage by lung infiltration with inflammatory MM in a cytokine release syndrome (CRS), a.k.a. cytokine storm. MM are attracted into the lungs by chemokines produced by lung epithelia and fibroblasts. MM are activated by GM-CSF and IL-6, therefore, a blockade with IL-6 receptor antibody (tocilizumab, ActemraR) is used in presence of a high inflammation [27]. CRS is related to the release of IL-1, IL-6 and nitric oxide (NO) from monocyte/macrophages, as shown in vitro and in an animal model by depletion of macrophages. CRS is similar to macrophage activation syndrome (MAS), a complication of several autoimmune diseases, in which well-differentiated macrophages show uncontrolled proliferation. CRS is also a complication of chimeric antigen receptor (CAR) therapy of B cell malignancies, in which macrophages produce IL-6, IL-1 and NO and where IL-1 blockade is therapeutic. COVID 19 pneumonia may be complicated by disseminated intravascular coagulation (DIC), therefore anticoagulation with enoxaparin (LovenoxR) is routinely used in severe CoV2 infections.
In COVID-19 pneumonia, macrophages have a dual role with a beneficial anti-viral role and a detrimental role through excessive release of inflammatory cytokines [28]. The lung has two types of macrophages, interstitial and alveolar macrophages. The alveolar macrophages with M1 type are pivotal in defense against pathogens by phagocytosis of microbes, enhancement of development of cytotoxic T cells and type I interferon production. The M2 type alveolar macrophages dampen the inflammation and repair the damage in association with other immune tissue cells. Macrophages infected by CoV2, however, accumulate lipid droplets in association with virus replication [29].
Angiotensin-converting enzyme 2 (ACE2) is a cell receptor for SARS and CoV-2 on lung epithelial cells. SARS-CoV-2 can infect monocytes and macrophages through ACE2-dependent and ACE2-independent pathways [27]. A second study with similar findings detected ACE2-expressing CD68+ and CD169+ macrophages containing SARS-CoV-2 nucleoprotein antigens in the sinuses of the lymph nodes of COVID-19 patients. These infected macrophages up regulated the pro-inflammatory cytokines IL-6 [30] and IL-1B [31]. The increased production of these cytokines by infected monocytes and macrophages induces hyper-inflammation and the onset of cytokine storm, leading to excess tissue damage and the potential harm of other vital organs in addition to the lungs (Figure 2) [27]. In addition, a subset of macrophages isolated from Covid-19 patients have been found to express genes that promote fibrosis generation and tissue repair. Therefore, the infection of infiltrating macrophages might not only be detrimental because of the promotion of acute inflammation, but also because of fibrotic complications that may arise and that have been observed in patients under mechanical ventilation. Long-term increases in the pro-inflammatory M1 type macrophages are associated with elevated reactive oxygen species (ROS) [32], which can produce harmful long-term side effects.
Figure 2.
Monocyte infiltration of the lungs with differentiation and activation of macrophages with production of cytokines and chemokines. Created with BioRender.com.
6. Macrophages in tuberculosis
Similar to in COVID-19 infections, macrophages play a dual role in tuberculosis. Macrophages permissive for M. tuberculosis (Mtb) replication, they may control and eliminate the infection in the presence of appropriate innate and acquired responses [4].
M1 and M2 macrophages are distinguished by their activation type. M1 cells are activated by the T helper type 1 (Th1) cells. These cells pertain to cell mediated immune responses and emit interleukin-2 (IL-2), IFN-γ, and lymphotoxins [33]. Th1 cells lead to an increased M1 activation due to the production of IFN-y. Nitric oxide production is stimulated by the Th1 activation, rather than T helper type 2 (Th2) cells [34]. Th2 cells cause the activation of M2 macrophages. These cells are responsible for the stimulation of humoral immunity and secrete interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-10 (IL-10). Th2 responses are a result of the production of ornithine which activates the M2 response allowing for tissue repair [1]. In tuberculosis, the intersection of Th1 and Th2 activation of M1 and M2 respectively leads to the immunity against pathogens. Along with the production of IFN-y, immunoglobulin A (Ig-A) is necessary for defense against tuberculosis (Table 2) [35].
Type 1 macrophages
Type 2 macrophages
Marker expression
CD80, CD54
CD163, CD206
Activation
Th1, INF-γ, GM-CSF
Th2, IL-4
Pro-inflammatory cytokines
High
Low
Antigen presentation
Yes
No
Production of ROS/NO
High
Low
Purpose
Destruction of microbes
Construct extracellular matrix
Table 2.
Type 1 and type 2 macrophage distinction.
Alveolar macrophages (AM) and dendritic cells phagocytize Mtb in the alveolar space in the lungs. Mtb is transmitted by macrophages to other organs via lymph nodes and blood vessels [36]. Alveolar macrophages present Mtb antigens to the adaptive immune cells to initiate an immune response. Subsequently, granulomas are formed because of the early inflammatory response caused by the AM [37]. Granulomas contain a variety of immune cells in order to contain the antigen. Some of the immune cells present in granulomas include foamy macrophages, epithelioid cells, neutrophils, and dendritic cells.
7. Conclusion
The phenotype of macrophages infiltrating the lesions in AD, ALS, HIV-1 myocarditis and encephalitis should be determined first, as it is the initial information necessary for analyzing macrophage role in each disease. M1 phenotype should be confirmed by staining of NOS, COX-2, TNF alpha, IL1, and IL-6 on macrophages.
Preliminary data suggest the following: (a) the pro-inflammatory M1 macrophage phenotype = CD54 + CD80/CD163 + CD206 > 4.0 is associated with an increased macrophage effector function in viral infections, but also with organ damage best known in HIV-1 myocarditis; b) the pro-resolution phenotype M1/M2 phenotype CD54 + CD80/CD163 + CD206 = in AD is associated with a beneficial role of macrophages in AD. The natural substances polyunsaturated fatty acids, vitamins B and D, energy molecules (carnitine), and flavonoids (resveratrol) may have individual health effects by improving macrophage transcriptome and macrophage pro-resolution type for brain clearance in AD, but the effects are complex and depend on many variables. In ALS patients, the M1/M2 phenotype promoted by fatty acids could be beneficial, but the data in human patients are not yet available.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"Alzheimer’s disease, amyotrophic lateral sclerosis, inflammatory response, cytokines, macrophage, transcriptome, glycome",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80219.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80219.xml",downloadPdfUrl:"/chapter/pdf-download/80219",previewPdfUrl:"/chapter/pdf-preview/80219",totalDownloads:51,totalViews:0,totalCrossrefCites:1,dateSubmitted:"December 20th 2021",dateReviewed:"December 25th 2021",datePrePublished:"March 24th 2022",datePublished:null,dateFinished:"January 25th 2022",readingETA:"0",abstract:"Macrophages have a critical role in the outcome of neurological diseases, including neurodegenerative, autoimmune, vascular and microbial diseases. Macrophage role ranges from beneficial to pathogenic depending upon genetics, other components of innate and adaptive immunity, lifestyle and macrophage targets: aggregated molecules or bacterial and viral pathogens. Macrophages are attracted by chemokines to migrate into the brain and remove or inactivate pathogenic molecules. In the patients with neurodegenerative diseases, macrophages target aggregated molecules, amyloid-β1–42 (Aβ) and P-tau in Alzheimer’s disease (AD), and superoxide dismutase-1 (SOD-1) in amyotrophic lateral sclerosis (ALS), but also have autoimmune targets. In AD and ALS patients, macrophages in the pro-resolution M1M2 state are adapted to brain clearance and homeostasis, whereas in the proinflammatory M1 state are modulate to an anti-viral and antibacterial role, which may be associated with collateral damage to tissues. In HIV-1 and CoV2 viral infections, macrophages in M1 state are anti-viral but also pathogenic through inflammatory damage to the heart and the brain. In neurodegenerative diseases, the natural substances polyunsaturated fatty acids (PUFA), vitamins B and D, energy molecules, and flavonoids have beneficial effects on macrophage transcriptome and functions for brain clearance, but the effects are complex and depend on many variables.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80219",risUrl:"/chapter/ris/80219",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar and Milan Fiala",book:{id:"11277",type:"book",title:"Macrophages -140 Years of Their Discovery",subtitle:null,fullTitle:"Macrophages -140 Years of Their Discovery",slug:null,publishedDate:null,bookSignature:"Dr. Vijay Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/11277.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-625-3",printIsbn:"978-1-80355-624-6",pdfIsbn:"978-1-80355-626-0",isAvailableForWebshopOrdering:!0,editors:[{id:"63844",title:"Dr.",name:"Vijay",middleName:null,surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Macrophages of Alzheimer’s disease patients fail in clearance of the AD brain",level:"1"},{id:"sec_2_2",title:"2.1 Natural substances have mixed results in prevention of Alzheimer’s disease",level:"2"},{id:"sec_3_2",title:"2.2 Alzheimer’s disease patients’ macrophages have transcriptomic defects that underlie their defective function",level:"2"},{id:"sec_4_2",title:"2.3 Natural substances have positive effects on macrophage biochemistry",level:"2"},{id:"sec_5_2",title:"2.4 Monoclonal antibodies and PUFA in therapy of AD",level:"2"},{id:"sec_7",title:"3. Macrophages in amyotrophic lateral sclerosis",level:"1"},{id:"sec_8",title:"4. Macrophages in HIV-1 infection",level:"1"},{id:"sec_9",title:"5. Macrophages in patients with COVID-19 infections",level:"1"},{id:"sec_10",title:"6. Macrophages in tuberculosis",level:"1"},{id:"sec_11",title:"7. Conclusion",level:"1"},{id:"sec_15",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: Different gene signatures in M1(LPS+) vs. classically and M2(LPS–) vs. alternatively activated macrophages. Frontiers in Immunology. 2019;10(1084)'},{id:"B2",body:'Famenini S, Rigali EA, Olivera-Perez HM, Dang J, Chang MT, Halder R, et al. Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on omega-3 supplementation. The FASEB Journal. 2017;31(1):148-160'},{id:"B3",body:'Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage M1-M2 polarization balance. Frontiers in Immunology. 2014;5:614'},{id:"B4",body:'Guirado E, Schlesinger LS, Kaplan G. Macrophages in tuberculosis: Friend or foe. Seminars in Immunopathology. 2013;35(5):563-583'},{id:"B5",body:'Fiala M, Liu QN, Sayre J, Pop V, Brahmandam V, Graves MC, et al. 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Amyotrophic Lateral Sclerosis. 2004;5:1-7'},{id:"B22",body:'Chiot A, Zaïdi S, Iltis C, Ribon M, Berriat F, Schiaffino L, et al. Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival. Nature Neuroscience. 2020;23(11):1339-1351'},{id:"B23",body:'Fiala M, Chattopadhay M, La Cava A, Tse E, Liu G, Lourenco E, et al. IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients. Journal of Neuroinflammation. 2010;7(1):76-90'},{id:"B24",body:'Fiala M, Looney DJ, Stins M, Way DD, Zhang L, Gan X, et al. TNF-alpha opens a paracellular route for HIV-1 invasion across the blood-brain barrier. Molecular Medicine. 1997;3(8):553-564'},{id:"B25",body:'Lipton JD, Schafermeyer RW. Central nervous system infections. The usual and the unusual. Emergency Medicine Clinics of North America. 1995;13(2):417-443'},{id:"B26",body:'Liu QN, Reddy S, Sayre JW, Pop V, Graves MC, Fiala M. 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EMBO Molecular Medicine. 2021;13(8):e14150'},{id:"B32",body:'Deng Z, Shi F, Zhou Z, Sun F, Sun MH, Sun Q, et al. M1 macrophage mediated increased reactive oxygen species (ROS) influence wound healing via the MAPK signaling in vitro and in vivo. Toxicology and Applied Pharmacology. 2019;366:83-95'},{id:"B33",body:'Dlugovitzky D, Torres-Morales A, Rateni L, Farroni MA, Largacha C, Molteni O, et al. Circulating profile of Th1 and Th2 cytokines in tuberculosis patients with different degrees of pulmonary involvement. FEMS Immunology & Medical Microbiology. 1997;18(3):203-207'},{id:"B34",body:'Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. Journal of Immunology. 2000;164(12):6166-6173'},{id:"B35",body:'Abebe F. Synergy between Th1 and Th2 responses during mycobacterium tuberculosis infection: A review of current understanding. International Reviews of Immunology. 2019;38(4):172-179'},{id:"B36",body:'Garcia-Romo GS, Pedroza-Gonzalez A, Lambrecht BN, Aguilar-Leon D, Estrada-Garcia I, Hernandez-Pando R, et al. Mycobacterium tuberculosis manipulates pulmonary APCs subverting early immune responses. Immunobiology. 2013;218(3):393-401'},{id:"B37",body:'Khan A, Singh VK, Hunter RL, Jagannath C. Macrophage heterogeneity and plasticity in tuberculosis. Journal of Leukocyte Biology. 2019;106(2):275-282'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Mary Dover",address:null,affiliation:'
Department of Integrative Physiology and Biology, UCLA School of Life Sciences, Los Angeles, California, USA
Department of Integrative Physiology and Biology, UCLA School of Life Sciences, Los Angeles, California, USA
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She is currently a professor for general education specializing in early childhood education (ECE) at the University of Vechta. For many years she has been the project director of the “Early Years Professional Development Initiative” (WiFF) at the German Youth Institute (DJI) in Munich. She is a reviewer for several educational journals, an active member in different research organizations (German Society of Science Education (DGFE), European Association for Research on Learning and Instruction (EARLI)), and board member of the Pestalozzi- Froebel-Association (pfv). Her research interests include enculturation and education in childhood, socio-cultural theory, Inclusive Education, and Diversity. 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Digital Science is a technology company serving the needs of scientific and research communities at key points along the full cycle of research. They support innovative businesses and technologies that make all parts of the research process more open, efficient and effective. IntechOpen integrates tools such as Altmetric to enable our researchers to track and measure the activity around their academic research and Dimensions, to ease access to the most relevant information and better understand and analyze the global research landscape.
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CLOCKSS
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CLOCKSS preserves scholarly publications in original formats, ensuring that they always remain available and openly accessible to everyone.
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Counter
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COUNTER provides the Code of Practice that enables publishers and vendors to report usage of their electronic resources in a consistent way. This enables libraries to compare data received from different publishers and vendors.
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DORA
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\\n\\t
DORA is a worldwide initiative covering all scholarly disciplines which recognizes the need to improve the ways in which the outputs of scholarly research are evaluated and seeks to develop and promote best practice. To date it has been signed by over 1500 organizations and around 14,700 individuals.
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iThenticate
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\\n\\t
iThenticate is the leading provider of professional plagiarism detection and prevention technology and is used worldwide by scholarly publishers and research institutions to ensure the originality of written work before publication. IntechOpen uses the iThenticate plagiarism software to ensure content originality and the research integrity of our published work.
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Enago
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\\n\\t
IntechOpen collaborates with Enago, through its sister brand, Ulatus, one of the world’s leading providers of book translation services. Their services are designed to convey the essence of your work to readers from across the globe in the language they understand.
\\n\\t
IntechOpen Authors that wish to use this service will receive a 20% discount on all translation services. To find out more information or obtain a quote, please visit https://www.enago.com/intech
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Straive
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Straive is the market leader in technology-driven solutions for the extraction, enrichment and transformation of content assets. IntechOpen publishing services are designed to meet the unique needs of Authors. As part of our commitment to that objective, we have an ongoing partnership agreement for production solutions.
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Amazon
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\\n\\t
Amazon is the world’s largest online retailer and cloud services provider. IntechOpen books have been available on Amazon since 2017, guaranteeing more visibility for our Authors and Academic Editors.
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DHL
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IntechOpen has partnered with DHL since 2011 to ensure the fastest delivery of Print on Demand books.
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United Nations Sustainable Development Goals Publishers Compact
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\\n\\t
The Compact is designed to inspire action among publishers. Launched in collaboration with the International Publishers Association, the Compact aims to accelerate progress to achieve the Sustainable Development Goals (SDGs) by 2030. Signatories aspire to develop sustainable practices and act as champions of the SDGs during the Decade of Action (2020-2030), publishing books and journals that will help inform, develop, and inspire action in that direction. Learn more here
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River Valley Technology
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\\n\\t
River Valley Technology is the world’s first XML-based publishing solution from submission to peer review to production and to final hosting, giving full control to publishers, with full transparency of data.
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Figshare
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\\n\\t
Figshare is an online open access repository where researchers can preserve and share their research outputs, including figures, datasets, images, and videos. It is free to upload content and free to access, in adherence to the principle of open data.
The Association of Learned and Professional Society Publishers (ALPSP) is the largest association of scholarly and professional publishers in the world. Its mission is to connect, inform, develop and represent the international scholarly and professional publishing community. IntechOpen has been a member of ALPSP since 2016 and has consequently stayed informed about industry trends through connecting with peers and developing jointly.
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OASPA
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\n\t
The Open Access Scholarly Publishers Association (OASPA) was established in 2008 to represent the interests of Open Access (OA) publishers globally in all scientific, technical and scholarly disciplines. Its mission is carried out through exchange of information, the setting of standards, advancing models, advocacy, education, and the promotion of innovation.
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STM
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\n\t
The International Association of Scientific, Technical and Medical Publishers (STM) is the leading global trade association for academic and professional publishers. As a member, IntechOpen has not only made a commitment to STM's Ethical Principles.
\n
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COPE
\n\n
\n\t
The Committee on Publication Ethics (COPE) provides advice to editors and publishers on all aspects of publication ethics and, in particular, how to handle cases of misconduct in research and publication. IntechOpen has been a member of COPE since 2013 and adheres to the COPE Code of Conduct and Best Practice Guidelines, ensuring that we maintain the highest ethical standards.
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Creative Commons
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Creative Commons (CC) is a nonprofit organization that enables the sharing and use of creativity and knowledge through free legal tools. IntechOpen uses the CC BY 3.0 license for chapters, meaning Authors retain copyright and their work can be reused and adapted as long as the source is properly cited and Authors are acknowledged.
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Crossref
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Crossref is the official Digital Object Identifier (DOI) Registration Agency for scholarly and professional publications with a goal of making scholarly communications more effective. IntechOpen deposits metadata and registers DOIs for all content using the Crossref System. IntechOpen also deposits its references and uses the Crossref Cited-by service that enables researchers to track citation statistics.
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Altmetric and Dimensions from Digital Science
\n\n
\n\t
Digital Science is a technology company serving the needs of scientific and research communities at key points along the full cycle of research. They support innovative businesses and technologies that make all parts of the research process more open, efficient and effective. IntechOpen integrates tools such as Altmetric to enable our researchers to track and measure the activity around their academic research and Dimensions, to ease access to the most relevant information and better understand and analyze the global research landscape.
\n
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CLOCKSS
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\n\t
CLOCKSS preserves scholarly publications in original formats, ensuring that they always remain available and openly accessible to everyone.
\n
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Counter
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\n\t
COUNTER provides the Code of Practice that enables publishers and vendors to report usage of their electronic resources in a consistent way. This enables libraries to compare data received from different publishers and vendors.
\n
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DORA
\n\n
\n\t
DORA is a worldwide initiative covering all scholarly disciplines which recognizes the need to improve the ways in which the outputs of scholarly research are evaluated and seeks to develop and promote best practice. To date it has been signed by over 1500 organizations and around 14,700 individuals.
\n
\n\n
iThenticate
\n\n
\n\t
iThenticate is the leading provider of professional plagiarism detection and prevention technology and is used worldwide by scholarly publishers and research institutions to ensure the originality of written work before publication. IntechOpen uses the iThenticate plagiarism software to ensure content originality and the research integrity of our published work.
\n
\n\n
Enago
\n\n
\n\t
IntechOpen collaborates with Enago, through its sister brand, Ulatus, one of the world’s leading providers of book translation services. Their services are designed to convey the essence of your work to readers from across the globe in the language they understand.
\n\t
IntechOpen Authors that wish to use this service will receive a 20% discount on all translation services. To find out more information or obtain a quote, please visit https://www.enago.com/intech
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\n\n
Straive
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\n\t
Straive is the market leader in technology-driven solutions for the extraction, enrichment and transformation of content assets. IntechOpen publishing services are designed to meet the unique needs of Authors. As part of our commitment to that objective, we have an ongoing partnership agreement for production solutions.
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\n\n
Amazon
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\n\t
Amazon is the world’s largest online retailer and cloud services provider. IntechOpen books have been available on Amazon since 2017, guaranteeing more visibility for our Authors and Academic Editors.
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DHL
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\n\t
IntechOpen has partnered with DHL since 2011 to ensure the fastest delivery of Print on Demand books.
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United Nations Sustainable Development Goals Publishers Compact
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\n\t
The Compact is designed to inspire action among publishers. Launched in collaboration with the International Publishers Association, the Compact aims to accelerate progress to achieve the Sustainable Development Goals (SDGs) by 2030. Signatories aspire to develop sustainable practices and act as champions of the SDGs during the Decade of Action (2020-2030), publishing books and journals that will help inform, develop, and inspire action in that direction. Learn more here
\n
\n\n
River Valley Technology
\n\n
\n\t
River Valley Technology is the world’s first XML-based publishing solution from submission to peer review to production and to final hosting, giving full control to publishers, with full transparency of data.
\n
\n\n
Figshare
\n\n
\n\t
Figshare is an online open access repository where researchers can preserve and share their research outputs, including figures, datasets, images, and videos. It is free to upload content and free to access, in adherence to the principle of open data.
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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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It is a leading cause of disability in children. Congenitally infected neonates often appear asymptomatic at birth or have nonspecific symptoms. An early diagnosis and subsequent early antiviral therapy associated to nonpharmacological therapy (e.g., hearing rehabilitation, speech-language therapy, and cochlear implants) can reduce long-term disability. Much research has been done in this field, but further studies are still necessary. Looking back at the most recent papers, we will draw a review on this topic trying to answer to the question: could universal CMV screening be a useful and cost-effective diagnostic tool?",book:{id:"8728",slug:"update-on-critical-issues-on-infant-and-neonatal-care",title:"Update on Critical Issues on Infant and Neonatal Care",fullTitle:"Update on Critical Issues on Infant and Neonatal Care"},signatures:"Sara Lunardi, Francesca Lorenzoni and Paolo Ghirri",authors:null},{id:"44446",doi:"10.5772/54310",title:"Neonatal Pneumonia",slug:"neonatal-pneumonia",totalDownloads:14794,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"2990",slug:"neonatal-bacterial-infection",title:"Neonatal Bacterial Infection",fullTitle:"Neonatal Bacterial Infection"},signatures:"Friedrich Reiterer",authors:[{id:"152025",title:"Prof.",name:"Friedrich",middleName:null,surname:"Reiterer",slug:"friedrich-reiterer",fullName:"Friedrich Reiterer"}]},{id:"70806",doi:"10.5772/intechopen.90885",title:"Neonatal Respiratory Distress Syndrome: Things to Consider and Ways to Manage",slug:"neonatal-respiratory-distress-syndrome-things-to-consider-and-ways-to-manage",totalDownloads:927,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Involving more commonly the premature (less than 37 weeks of gestational age) infants, neonatal respiratory distress syndrome is an important clinical syndrome responsible for a high rate of mortality and morbidity. The main progress in respiratory distress syndrome (RDS) management is attributable to prescription of surfactant for fastening pulmonary maturation. Respiratory protection, such as mechanical ventilation and nasal continuous positive airway pressure, and surfactant are building blocks of disease treatment. In this chapter, we are going to have a rapid review on epidemiology, diagnosis and treatments of RDS.",book:{id:"8728",slug:"update-on-critical-issues-on-infant-and-neonatal-care",title:"Update on Critical Issues on Infant and Neonatal Care",fullTitle:"Update on Critical Issues on Infant and Neonatal Care"},signatures:"Bita Najafian and Mohammad Hossein Khosravi",authors:[{id:"214323",title:"Dr.",name:"Mohammad Hossein",middleName:null,surname:"Khosravi",slug:"mohammad-hossein-khosravi",fullName:"Mohammad Hossein Khosravi"},{id:"308156",title:"Dr.",name:"Bita",middleName:null,surname:"Najafian",slug:"bita-najafian",fullName:"Bita Najafian"}]}],mostDownloadedChaptersLast30Days:[{id:"44446",title:"Neonatal Pneumonia",slug:"neonatal-pneumonia",totalDownloads:14796,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"2990",slug:"neonatal-bacterial-infection",title:"Neonatal Bacterial Infection",fullTitle:"Neonatal Bacterial Infection"},signatures:"Friedrich Reiterer",authors:[{id:"152025",title:"Prof.",name:"Friedrich",middleName:null,surname:"Reiterer",slug:"friedrich-reiterer",fullName:"Friedrich Reiterer"}]},{id:"53683",title:"Pre and Postoperative Management of Pediatric Patients with Congenital Heart Diseases",slug:"pre-and-postoperative-management-of-pediatric-patients-with-congenital-heart-diseases",totalDownloads:4931,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Stabilization during preoperative cardiac surgery especially in neonates has an important role to predict outcome for pediatric congenital heart surgery. We tried to elaborate general guidelines on how to diagnose and some anticipations for emergency treatments tailored by the type of congenital heart disease in neonates. Stabilization consists of medical treatment including emergent prostaglandin institution in some types of duct dependent lesion. The role of interventional catheterization such as patent ductus arteriosus (PDA) stent, balloon pulmonary valvotomy, etc. as modalities for stabilization before surgery was also elaborated. Some general and specific guidelines based on the type of surgeries for postoperative management were also discussed.",book:{id:"5473",slug:"pediatric-and-neonatal-surgery",title:"Pediatric and Neonatal Surgery",fullTitle:"Pediatric and Neonatal Surgery"},signatures:"Eva Miranda Marwali, Beatrice Heineking and Nikolaus A. 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It is more common during the neonatal period than at any other age with the estimated incidence of 0.25 per 1000 live births. The absence of specific clinical presentation makes diagnosis of meningitis more difficult in neonates than in older children. Culture of cerebrospinal fluid is the traditional gold standard for diagnosis of bacterial meningitis, so all newborn infants with proven or suspected sepsis should undergo lumbar puncture. However, deciding when to perform lumbar puncture and interpretation of the results are challenging. Although the pathophysiology of neonatal meningitis is complex and not fully understood, researches on diagnostic and prognostic tools are ongoing. Prevention of neonatal sepsis, early recognition of infants at risk, development of novel, rapid diagnostics and adjunctive therapies, and appropriate and aggressive antimicrobial treatment to sterilize cerebrospinal fluid as soon as possible may prevent the lifelong squeal of bacterial meningitis in newborn infants.",book:{id:"7527",slug:"neonatal-medicine",title:"Neonatal Medicine",fullTitle:"Neonatal Medicine"},signatures:"Mehmet Şah İpek",authors:[{id:"267903",title:"Associate Prof.",name:"Mehmet Şah",middleName:null,surname:"İpek",slug:"mehmet-sah-ipek",fullName:"Mehmet Şah İpek"}]},{id:"71427",title:"Factors Influencing Maternal Decision-Making on Infant Feeding Practices",slug:"factors-influencing-maternal-decision-making-on-infant-feeding-practices",totalDownloads:1014,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The decision to formula feed or breastfeed a child typically begins with an established prenatal intention. This chapter will examine the multiple dimensions influencing maternal decision-making in regards to the feeding practices of infants including 1) individual maternal characteristics, 2) organizational factors, 3) hospital/provider recommendations, and 4) systematic/policy factors. The chapter will also examine the impact of infant feeding practices on early infant and childhood health outcomes. Research has demonstrated the benefits of breastfeeding on infants and early childhood which includes but is not limited to protection against common illnesses and infections, improved IQ , and even increased school attendance. Moreover, the World Health Assembly global nutrition objectives focus on encouraging breastfeeding support across all sectors in addition to implementing tailored community-based approaches, limiting the excessive marketing of infant formula, and enforcing supportive breastfeeding legislation. The aim of this chapter is to provide an overview of the dynamic interplay between individual, interpersonal, community, and societal factors, such as policies that impact breastfeeding rates and more specifically the health of infants.",book:{id:"9805",slug:"infant-feeding-breast-versus-formula",title:"Infant Feeding",fullTitle:"Infant Feeding - Breast versus Formula"},signatures:"Whitney N. 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Reaching all rightly and robustly is required. All this will contribute greatly towards the growth & development of infants and grandly towards the Sustainable Development Goals. We propose the “ABC mothers” plan. Progress for required practices for results possible with making mothers—“Able for practices advantageous, bold with pertinent awareness, and confident with propitious attitude”. Strong efforts on sound footing are necessary for health of all our infants and happiness all around with sustainable development. Scientific infant feeding will contribute to advance the attainment of this. Medical education teaching best beneficial practices is for excellence. One promoting breastfeeding is the best. The US Surgeon General’s Implementation Strategies elaborate “Education content”, “Enabling competency”, & “Education continuing”. Competency-based curriculum for Indian Medical Graduates includes “to promote and support optimal breast feeding”. Need for inclusion in teaching curriculum across US, UK, & internationally has been documented. Given all the evidence for breastfeeding benefits, it should be a consistent essential component of training in all medical schools worldwide.",book:{id:"11308",title:"Selected Topics on Infant Feeding",coverURL:"https://cdn.intechopen.com/books/images_new/11308.jpg"},signatures:"Sunil Jain, Arvind Singh Kushwaha and Vishal Marwaha"},{id:"81544",title:"Infant and Young Child Feeding in the Developed and Developing Countries",slug:"infant-and-young-child-feeding-in-the-developed-and-developing-countries",totalDownloads:33,totalDimensionsCites:0,doi:"10.5772/intechopen.103012",abstract:"Infant feeding challenges continue to manifest in developed and developing countries. Worldwide, more than 80% of babies are breastfed in the first few weeks of birth. However, about 37%, 25%, and less than 1% are exclusively breastfed at 6 months of age in Africa, the United States of America, and the United Kingdom, respectively. These statistics are far below the World Health Organization targets of 50% and 70% by 2025 and 2030, respectively. Complementary feeding practices are varied as well due to nonadherence to Infant and Young Child Feeding (IYCF) guidelines among parents. This accounts for the current trends in malnutrition in children under−5 years of age, adolescents, and the youth, and leads to intergeneration malnutrition. In this chapter we have included sections on appropriate infant feeding; including how to initiate breastfeeding in the first hour of birth, how to exclusively breastfeed infants until 6 months of age, how to complement breastfeeding after 6 months of infant’s age as well as continuing to breastfeed until 24 months of age and even beyond. Furthermore, we have included a description of how mothers who are unable to breastfeed can feed their infants on expressed breastmilk or replace breastmilk with appropriate homemade or commercial formula. This chapter as well covers infant feeding in prematurity.",book:{id:"11308",title:"Selected Topics on Infant Feeding",coverURL:"https://cdn.intechopen.com/books/images_new/11308.jpg"},signatures:"Enos Mirembe Masereka, Clement Munguiko, Alex Tumusiime and Linda Grace Alanyo"},{id:"81207",title:"Breastfeeding during COVID Pandemic",slug:"breastfeeding-during-covid-pandemic",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.104604",abstract:"As new mothers are understandably concerned about COVID-19 and its high rate of infection, they are often unsure if they should breastfeed their infants. In general, hospitals do not allow direct breastfeeding by mothers with an active infection of SARS-CoV-2. Some neonatal units in Hong Kong maintain safe practices by isolating infants and mothers for at least 7 to 14 days, even if the infant remains SARS-CoV-2 negative. During isolation, mothers encourage the expression of milk to maintain milk duct patency and to prepare for lactation when they and their infants are discharged. Infants are fed formula milk by cup feeding with added supplements based on the recommended daily feeding volume for neonates and their appetite during hospitalization. At present, data that indicates COVID-19 could be transmitted from mother to infant postnatally through breastfeeding are insufficient. Major organizations recommend that mothers should breastfeed exclusively for the first 6 months, and thereafter continue to provide their infants with breast milk up until the age of two or beyond. With new findings arising from research, updated information is important to reassure mothers that breastfeeding at home during the COVID-19 pandemic is safe and recommended for both the mother and the infant.",book:{id:"11308",title:"Selected Topics on Infant Feeding",coverURL:"https://cdn.intechopen.com/books/images_new/11308.jpg"},signatures:"Ka-Huen Yip, Mei-Kuen Chow, Yuk-Chiu Yip and Wai-King Tsui"},{id:"81129",title:"Research of Fat Component Safety and Pre-Clinical Evaluation of Infant Adapted Dry Milk Mixtures Physiological Effect",slug:"research-of-fat-component-safety-and-pre-clinical-evaluation-of-infant-adapted-dry-milk-mixtures-phy",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.103069",abstract:"The aim of the study deals with determination of fat component safety and quality key indicators of adapted infant dry milk formulas provided by various manufacturers. The most popular in Russia adapted infant dry milk formulas were selected as study objects. It was found that the qualitative composition of the fat component of dry milk mixtures corresponds to the information placed on the package. However none of the samples under study in terms of the average composition of the prevailing fatty acids fully corresponds to human breast milk. The regulation documents of the Customs Union (TR CU 021/2011, TR CU 024/2011, TR CU 033/2013) establish only the organoleptic evaluation of the adapted breast milk formulas quality indicators. Among the fat component safety indicators only the determination of the peroxide value characterizing the accumulation of primary fat oxidation products. It was also found that the peroxide values of the studied mixtures do not exceed the regulated values. Meanwhile the samples of infant milk food made from dry milk mixtures almost all have unsatisfactory organoleptic characteristics. Defects of taste and smell are associated with the accumulation in the original adapted milk mixtures of a significant amount of secondary products of fat oxidation, which in a biological experiment on animals lead to a decrease in the content of leukocytes and a change of its blood count.",book:{id:"11308",title:"Selected Topics on Infant Feeding",coverURL:"https://cdn.intechopen.com/books/images_new/11308.jpg"},signatures:"Ekaterina Yurievna Volf, Inna Vladimirovna Simakova, Andrey Anatolyevich Terentyev, Aleksandr Sergeevich Fedonnikov, Nina Viktorovna Bolotova, Gloria Vladimirovna Guzeeva and Viktor Veniaminovich Zakrevsky"}],onlineFirstChaptersTotal:4},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:"2753-6580",scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. Her publications cover a wide range of scientific and technical research publications that include edited books, book chapters, refereed journals, refereed conference papers and reports for local, state and federal government clients. She has also produced podcasts for various organisations and participated in media interviews. She has received state, national and international funding worth over USD $25 million. Usha has been awarded the Quarterly Franklin Membership by London Journals Press (UK). Her biography has been included in the Marquis Who's Who in the World® 2018, 2016 (33rd Edition), along with approximately 55,000 of the most accomplished men and women from around the world, including luminaries as U.N. Secretary-General Ban Ki-moon. 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Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. 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She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain.Dr. Satué is accredited as a Private University Doctor Professor, Doctor Assistant, and Contracted Doctor by AVAP (Agència Valenciana d'Avaluació i Prospectiva) and currently, as a full professor by ANECA (since January 2022). To date, Katy has taught 22 years in the Department of Animal Medicine and Surgery at the CEU-Cardenal Herrera University in undergraduate courses in Veterinary Medicine (General Pathology, integrated into the Applied Basis of Veterinary Medicine module of the 2nd year, Clinical Equine I of 3rd year, and Equine Clinic II of 4th year). Dr. Satué research activity is in the field of Endocrinology, Hematology, Biochemistry, and Immunology in the Spanish Purebred mare. She has directed 5 Doctoral Theses and 5 Diplomas of Advanced Studies, and participated in 11 research projects as a collaborating researcher. She has written 2 books and 14 book chapters in international publishers related to the area, and 68 scientific publications in international journals. Dr. Satué has attended 63 congresses, participating with 132 communications in international congresses and 19 in national congresses related to the area. Dr. Satué is a scientific reviewer for various prestigious international journals such as Animals, American Journal of Obstetrics and Gynecology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology, among others. Since 2014 she has been responsible for the Clinical Analysis Laboratory of the CEU-Cardenal Herrera University Veterinary Clinical Hospital.",institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"439435",title:"Dr.",name:"Feda S.",middleName:null,surname:"Aljaser",slug:"feda-s.-aljaser",fullName:"Feda S. Aljaser",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"423023",title:"Dr.",name:"Yosra",middleName:null,surname:"Soltan",slug:"yosra-soltan",fullName:"Yosra Soltan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"349788",title:"Dr.",name:"Florencia Nery",middleName:null,surname:"Sompie",slug:"florencia-nery-sompie",fullName:"Florencia Nery Sompie",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sam Ratulangi University",country:{name:"Indonesia"}}},{id:"428600",title:"MSc.",name:"Adriana",middleName:null,surname:"García-Alarcón",slug:"adriana-garcia-alarcon",fullName:"Adriana García-Alarcón",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"428599",title:"MSc.",name:"Gabino",middleName:null,surname:"De La Rosa-Cruz",slug:"gabino-de-la-rosa-cruz",fullName:"Gabino De La Rosa-Cruz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"428601",title:"MSc.",name:"Juan Carlos",middleName:null,surname:"Campuzano-Caballero",slug:"juan-carlos-campuzano-caballero",fullName:"Juan Carlos Campuzano-Caballero",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}}]}},subseries:{item:{id:"28",type:"subseries",title:"Animal Reproductive Biology and Technology",keywords:"Animal Reproduction, Artificial Insemination, Embryos, Cryopreservation, Conservation, Breeding, Epigenetics",scope:"The advances of knowledge on animal reproductive biology and technologies revolutionized livestock production. Artificial insemination, for example, was the first technology applied on a large scale, initially in dairy cattle and afterward applied to other species. Nowadays, embryo production and transfer are used commercially along with other technologies to modulate epigenetic regulation. Gene editing is also emerging as an innovative tool. This topic will discuss the potential use of these techniques, novel strategies, and lines of research in progress in the fields mentioned above.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11417,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. 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