Vaccine effectiveness of two dose of vaccines against symptomatic infection and severe disease caused by non-VOCs, alpha, and Delta VOCs.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"3232",leadTitle:null,fullTitle:"Organic Farming and Food Production",title:"Organic Farming and Food Production",subtitle:null,reviewType:"peer-reviewed",abstract:'Organic farming does not mean going "back" to traditional (old) methods of farming. 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The general chemical formula of a perovskite material is ABX3, which contains a crystal structure similar to CaTiO3. It was initially discovered by German geologist Gustav Rose in 1839 in Ural Mountains, and named after Russian mineralogist Lev Perovski [1, 2]. In ABX3 perovskite, A and B are termed as metal cations having ionic valences combined to +6, e.g., (Li+:Nb5+; Ba2+:Ti4+; Sr2+:Mn4+; La3+:Fe3+) and X is an electronegative anion with ionic valence −2 such as O2−, S2− etc. [3, 4, 5, 6]. The perovskite materials may be oxides, halides, nitrides, sulfides, etc., and they may exist in different forms, such as powders, thin films, etc. [7, 8, 9, 10]. The perovskite material has attracted our attention as it can house up a variety of cations at A- and B-sites individually and/or simultaneously along with anions at X-site [11, 12]. The perovskite materials can be classified in ideal and distorted perovskite materials.
\nAn ideal perovskite material crystallizes into a simple cubic structure with \n
Molecular structures for ABX3 perovskite with
The family of perovskite material includes numerous types of oxide forms, such as transition metal oxides with the general formula of ABO3. The oxide perovskite materials are widely synthesized and are studied for wide applications in various technological fields. In light of these properties, we describe oxide perovskites in more detail.
\nVictor Moritz Goldschmidt presented an empirical relationship among the ionic radii of A, B, and O, known as tolerance factor (t) to estimate the stability of a perovskite structure. This relation is valid for the relevant ionic radii at room temperature [15]. The numerical value of the tolerance factor can be found by Eq. (1):
\nwhere, the term rA is the ionic radius of cation A and that of rB is ionic radius of B cation whereas rO is the ionic radius of oxygen anion (O2−). The ionic radius of A cation is always larger than that of the B cation. The tolerance factor provides an idea about the selection of combination of A and B cations in order to prepare an ideal perovskite material. Eq. (1) can also be expressed in other form, which may be valid for any temperature as given by Eq. (2):
\nwhere dA-O and dB-O are average bond-lengths between A-O and B-O, respectively [16].
\nThe distorted perovskite materials are those materials, which crystallize into other than the cubic structures. As far as we know that the perovskite material can accommodate different ions at the A- and B-sites. The variation in the A- and/or B-sites cations causes a variation in the tolerance factor. The variation in tolerance factor leads to a change in the perovskite structure from cubic to non-cubic distorted perovskite structure. For a stable perovskite, the value of tolerance factor should lie in the range of 0.88–1.09 [17]. An ideal perovskite crystal exhibits tolerance factor equal to unity (i.e., t = 1). For t < 1, the perovskite materials show the rhombohedral or monoclinic structure while in the case of t > 1; it reveals tetragonal or orthorhombic structure [18]. Due to distortion in the perovskite system, the BO6 octahedral led tilted from an ideal situation and causes a change/enhancement in unit cell volume. Thus, the tolerance factor is a measure of the extent of distortion in the perovskite structure. \nFigure 2\n shows unit cells for some distorted perovskite structures.
\nDifferent distorted perovskite unit cells; (a) tetragonal, (b) orthorhombic, (c) hexagonal, and (d) rhombohedral. Red spheres stand for oxygen anions.
There are two general requirements for the formation of a perovskite material, which are given as:
\n
\n
The pure perovskite materials (ABO3) do not always provide the desired properties. In order to make them useful, the doping at A- and/or B-sites is required. Doping at A- and/or B-sites improves the properties and also generates very interesting phenomena due to change in crystal structure, bond-lengths, ionic states, etc. The general chemical formula of A- and B-sites after doping in the perovskite matrix may be found in the form of A1-xA′xBO3 (0 < x < 1) and AB1-yB′yO3 (0 < y < 1), respectively. However, the simultaneous A- and B-sites doped oxide perovskites have general formula A1-xA′xB1-yB′yO3. Recently, there are several reports on lanthanide-based rare-earth doped perovskites [21, 22, 23, 24]. Initially, we discuss the synthesis process used for the preparation of rare-earth doped perovskite materials alongwith their phase identification, structural analysis by Rietveld refinement of X-ray diffraction (XRD) patterns, morphological and optical properties.
\nAs we know that the physical, chemical, and optical properties of the perovskite materials are strongly synthesis route dependent. One has to choose a suitable synthesis method to obtain the desired properties from the prepared materials. Synthesis techniques also affect crystal structure and morphology of the samples [25]. The synthesis techniques can be divided into three main classes as given below:
Solid-state synthesis
Liquid-state synthesis
Gas-state synthesis
These techniques have their own advantages. Solid-state methods are used to synthesize bulk materials, while liquid-state techniques are used to produce nanomaterials. However, gas-state methods are mostly used to fabricate thin films. In this, we will discuss these techniques one by one by taking some suitable examples.
\nSolid-state synthesis technique is used to produce polycrystalline materials. It is also known as ceramic method because most of the ceramics are synthesized by this method. This is most widely used technique by researchers. This method requires raw materials in carbonates and/or oxides forms. In this method, the raw materials do not react chemically to each-other at room temperature. When the nixture of raw materials is heated at very high temperatures (i.e., 700–1500°C), the chemical reaction takes place at a significant rate.
\nIt is one of the solid-state synthesis methods used for the production of bulk perovskite materials. Synthesis of perovskites using this method involves grinding, hand mixing, ball milling, and firing of starting materials in many times. In this case, the raw materials used in oxides and/or carbonates forms are grinded, hand mixed, ball milled, and calcined at a high temperature.
\nLet us describe the whole procedure of this synthesis technique by taking an example of Ca0.97-xTiO3:3Yb3+,xBi3+ perovskite phosphor. For the synthesis of CaCO3, TiO2, Yb2O3, and Bi2O3 were used as the raw materials. First of all, these materials were weighed in the stoichiometric amounts and grinded and mixed by hand in mortor by using pestle for 1–2 h. After hand mixing and grinding of all the starting materials, the mixture was ball milled in a planetary ball milling system to further get homogeneous mixture in the presence of acetone/alcohol as a mixing media for 4–12 h at a nominal rpm (round per minute) of 25–100 in clockwise and anticlockwise directions. After the ball milling, the homogeneous mixture was dried at ordinary temperature and divided into various parts for calcination at different temperatures from 600 to 1500°C for 4–30 h to optimize the pure phase. These phosphors were then structurally and optically characterized [26]. The perovskites prepared using this method have particles size in the submicrometer range [27]. Some other rare earths doped R0.5Ba0.5CoO3 (R = La, Pr, Nd, Sm, Eu, Gd, Tb, Dy) perovskites were also synthesized using this method [28].
\nThis technique is very similar to that of mechanical ball-milling technique. Only difference is that this method used very high rpm from few hundreds to few thousands for milling with very small sized balls. This technique uses low temperature for the synthesis of the oxide materials. This method produces generally the nanoparticles. This method only takes metal oxides because there is very high possibility of chemical reactions during high energy ball-milling, which may yield different toxic gases.
\nNow, let us describe the whole process by considering an example of 0.7BiFeO3–0.3PbTiO3 (BF-PT) solid solution [29]. The stoichiometric amounts of Bi2O3, Fe2O3, PbO, and TiO2 were taken as raw materials to prepare BF-PT and were mixed using agate mortar and pestle. Then the raw materials were ball-milled for 12–30 h with zirconia balls using alcohol as mixing media in the ratio of 1:10 with the sample and balls at 300–1000 rpm. Here, acetone or acid is not used for the purpose of mixing of raw materials as it may damage the milling jars and O-rings. The material dried at 90°C was annealed at various temperatures (i.e., 400–900°C) to optimize the pure phase of the sample. The XRD pattern of the samples was recorded to check the purity of the synthesized perovskite materials.
\nFor additional characterizations, such as dc poling and dielectric measurements, the annealed sample was mixed in 2% aqueous solution of PVA (polyvinyl alcohol) as binder and a pellet was made. The pellet of the perovskites was fired at 500°C for 10–12 h to burn out the PVA binder. Then the pellet was sintered at quite higher temperatures than annealing temperature to obtain the highly dense perovskite material. To further check the purity of the samples after sintering, the XRD pattern was recorded [30]. Sometimes, this method is also used to decrease the particles size from a micrometric scale to nanometric scale. \nFigure 3\n represents flow chart of the preparation procedures for the synthesis of perovskite materials using solid-state synthesis technique.
\nA representative flow-chart for the synthesis of oxide materials using ball milling technique.
The liquid-state synthesis technique is a method of synthesis of nanomaterials. It is most widely used by researchers and scientists for the production of nanoparticles of the oxide materials. In this method, the raw materials may be in the form of nitrates, acetates or oxalates, which may react to each other at an ordinary temperature. Auto-combustion, sol-gel, co-precipitation, etc. are different liquid-state synthesis techniques used for the preparation of perovskite nanomaterials, which are to be described in more detail [19].
\nThe auto-combustion synthesis method is a low-cost and very facile technique for the production of perovskite nanomaterials. In this technique, the starting materials are used in oxalates and/or acetates and/or nitrates forms, which are easily soluble in de-ionized water. It involves some organic fuel, such as urea, citric acid, and glycine to assist the combustion.
\nLet us describe the process of synthesis of the perovskite materials using auto-combustion method (see \nFigure 4(a)\n) with the help of an example of La0.7Sr0.3MnO3 manganite. Kumar et al. have synthesized La0.7Sr0.3MnO3 perovskite manganite using the starting materials as La2O3, SrCO3, and Mn(CH3COO)2.4H2O and glycine was used as fuel. First of all, La2O3 and SrCO3 were dissolved in diluted nitric acid to prepare their respective nitrates and then Mn(CH3COO)2.4H2O and glycine were dissolved into distilled water. All the prepared precursor solutions of the materials were dissolved/prepared independently and at the end, they were mixed simultaneously under nonstop stirring in a large beaker and heated on a magnetic stirrer at 175–200°C [31]. After continuous stirring of 6–7 h, the mixed solution became thicker and converted into gel, with further increase in time of stirring, an auto-ignition takes place resulting in flame that evolves huge amount of different gases. During the ignition process, the temperature of the whole mixture may reach upto 800–1000°C for very short time duration. The obtained blackish-brown powder was collected from the beaker and divided into various parts for the calcination at different temperatures. The La0.7Sr0.3MnO3 perovskite comes up with different particles size range. They have also prepared bulk samples of Ba1-xSrxMnO3 perovskites using the same method [32]. The CaTiO3:Pr3+, Al3+ phosphor was also prepared by Yin et al. using combustion method [33].
\nSchematic flow charts for the synthesis of oxide nanomaterials via (a) auto-combustion and (b) sol-gel methods.
The sol-gel method is used by most of the chemists for producing nanomaterials. This technique comprises both types of processes (physical and chemical) associated with the following, such as hydrolysis, condensation, polymerization, gelation, drying, and densification [34]. In this technique, the starting materials are used in the form of metal alkoxides. The general chemical formula of metal alkoxides is M(OR)x. Metal alkoxides can be assumed either a derivative of the alcohol ROH, where R is an alkyl group or a derivative of metal hydroxide M(OH)x [35]. The stoichiometric amounts of metal alkoxides are weighed and dissolved in alcohol or in de-ionized water at a temperature of 60–80°C under steady stirring. It is very important to control the pH value of the metal alkoxides solutions to avoid the formation of the precipitation and to form the homogeneous gel that can be achieved by using basic or acidic solutions. This is known as hydrolysis and condensation leads to form the polymeric chains. The progress of the polymeric chains eventually results to a perceptible improvement in the viscosity of the reaction mixture and the formation of a gel. The obtained gel is to be dried in temperature range between 150 and 200°C to remove the unwanted contents from the gel [35, 36]. After the removal of contents, the obtained gel was annealed at various temperatures in 400–800°C range to obtain the pure phased materials.
\nLet us discuss the practical processes involve in this technique by taking an example of La0.6Ca0.4MnO3 perovskite. Andrade et al. have synthesized nanotubes and nanoparticles of La0.6Ca0.4MnO3 perovskite manganite using sol-gel method following calcination at different temperatures [37]. They have used stoichiometric amounts of La(NO3)3.6H2O, CaCO3 and Mn(CH3COO)2.4H2O for the synthesis of La0.6Ca0.4MnO3 perovskite. The CaCO3 was dissolved in nitric acid to convert into calcium nitrate, while La(NO3)3.6H2O and Mn(CH3COO)2.4H2O were dissolved in distilled water. All the solutions were mixed together in a beaker. The appropriate amount of polyethylene glycol (PEG) was incorporated to the precursor solutions playing the role of polymerizing agent. Then the solution was heated at 70°C for 6 h to complete the polymerization process. At last, the whole solution was converted in yellow viscous gel, which was calcined at different temperatures from 700 to 1000°C. \nFigure 4(b)\n displays a representative flow chart of the processes involved in the synthesis of perovskite materials using sol-gel method
The co-precipitation method is also one of the methods used of the production of nanomaterials. This method needs raw materials of metal cations from a general medium and precipitates in the form of oxalates, carbonates, citrates or hydroxides [38, 39, 40, 41]. The resultant precipitates are several times washed with distilled water and then obtained product was calcined at various temperatures to acquire the pure phase of the desired materials in the polycrystalline form. This method can yield almost homogeneous polycrystalline powders. The solubility of the used compounds should be very close to each other for a proper precipitation [42]. The precursor solutions are mixed at atomic level resulting lower particles size and it requires very low calcination temperature to get a pure material [43]. The controlling pH of the precursor solution, stirring speed, concentration, and temperature of the mixture are important parameters for the co-precipitation method [44].
\nThe LaMn1-xFexO3 (x = 0, 0.1, 0.2) perovskite synthesized by Geetha et al. is an example of the co-precipitation method [45]. The stoichiometric amounts of La(NO3)3.6H2O, Fe(NO3)3.9H2O and MnCl2.4H2O were dissolved in distilled water. These solutions were mixed at one platform and stirred continuously at 50°C for 30 min. After this, NaOH solution was added slowly until the pH of solution is attained to 13. The mixed solution of the precursors was again stirred constantly till the formation of black precipitate. The precipitate was collected and washed many times to remove the excess of chlorides and kept in an oven to dry at 50°C. Thus, the final product was calcined at 800°C for 6 h.
\nIt was observed that liquid-state technique produces nanoparticles of perovskite materials at very low temperature. However, the sub-micron sized perovskite materials can be obtained by firing them at higher temperature similar to solid-state technique.
\nGas-state synthesis technique is also used to prepare the nanoparticles. It contains various procedures for the synthesis of powder oxide materials, viz. furnaces, flames, plasmas, and lasers. The basics of thermodynamics and kinetics of the reaction are very similar to each other; however, their reactors are different. These methods provide narrow distribution of the nanoparticles. The dispersion must be reduced for narrow distribution of the nanoparticles as it leads to increase the particles size [25]. Gas-state synthesis technique is a bottom-up method for the synthesis of multifunctional nanoparticles. Method of bottom-up nanofabrication is based on the gathering of nanomaterials from smaller components.
\nA variety of electronic devices and solar cells of perovskite materials are prepared in terms of thin films via these techniques and they are entirely different from the other synthesis techniques. There are various techniques for the preparation of thin films, such as chemical vapor deposition [46], molecular beam epitaxy [47], laser ablation [48], DC sputtering [49], magnetron sputtering [50], thermal evaporation [51], and electron beam evaporation [52]. The gas-state synthesis method needs particular set up for a good quality of samples to offer the preferred properties. The gas-state synthesis techniques are categorized into three types:
Fabrication at the crystallization temperature under a suitable atmosphere condition of temperature.
Fabrication in an intermediate temperature range (500–800°C) followed by post-annealing treatment at higher temperatures.
Fabrication at a very low substrate temperature followed by post-annealing treatment at very high temperature.
The perovskite materials fabricated using gas-state techniques have variety of applications ranging from optical and anticorrosion coatings to photocatalysts and solar cells, from semiconductor devices to capacitor dielectrics, from bio-implantable devices to chemical reactors and catalysts. One can undoubtedly say that the industrial interest for preparing nanomaterial-based technologies through gas-state synthesis is going to increase in the upcoming years.
\nIt is very important to check the phase and its purity of synthesized perovskite materials. Without knowing the phase purity, one cannot come to any conclusion about the properties exhibited by the perovskite materials. The XRD technique is a suitable tool to identify the phase of perovskites. From the XRD data, one can find out relative phase fractions of different phases present in the prepared samples. One can also find out lattice constants, unit cell volume, crystallite size, lattice strain, and theoretical density from Rietveld refinement of the XRD pattern. The XRD technique is also used to optimize the synthesis conditions for the perovskite materials. By matching the XRD pattern of the synthesized material with the standard XRD pattern of the cubic phase of CaTiO3 (CT) perovskite, one can conclude about the phase purity, i.e., whether, the perovskite is pure or has some amount of impurity phase(s) or crystallizes in the distorted perovskite. \nFigure 5\n shows the XRD pattern of the cubic CT perovskite with JCPDS File No. 75-2100 using X-ray radiation of 1.5406 Å wavelength. The analysis of XRD pattern gives unit cell lattice parameter a = 3.795 Å and unit cell volume V = 54.656 Å3. An ideal perovskite material displays reflections from all allowed planes of the primitive unit cell. It shows most intense XRD peak for (1 1 0) plane in the 2θ range of 32–34° and first singlet reflection corresponding to (1 0 0) plane between 22 and 24°.
\nThe standard XRD pattern for the cubic phase of CaTiO3 perovskite.
As we know that the different materials display different XRD patterns as like the finger print of the humans. However, a certain prototype of materials gives the XRD pattern in a well-defined manner. In order to make sure that the synthesized sample is perovskite or not, we have to match the XRD pattern of the synthesized sample with the XRD pattern of CT. If it matches it forms a perovskite phase otherwise not.
\n\n\nFigure 6(a)\n shows the room-temperature XRD pattern for BaTiO3 (BT) synthesized by mechanical ball-milling method followed by calcination at 950°C for 5 h and it is compared with XRD pattern of CT. The comparison of both the XRD patterns reveals that the XRD pattern of BT matches with that of the CT. This further confirms that BT is a perovskite material. The Bragg’s peaks in XRD pattern of BT perovskite is shifted towards lower angle side compared to CT. This indicates that the lattice parameters of BT are larger than that of the CT. Furthermore, the Bragg peak around 22° is asymmetric in lower angle side, which shows doublet nature in the peak, i.e., the lattice plane (1 0 0) of CT split into (0 0 1) and (1 0 0) of BT is shown as inset in \nFigure 6(a)\n. Similarly, the other Bragg’s peaks also show asymmetrical behavior. All these observations reveal that the crystal structure of BT is distorted from an ideal perovskite structure. The Rietveld refinement of XRD pattern of BT reveals that the BT crystallizes into tetragonally distorted structure with
(a) Room temperature XRD pattern of BaTiO3 compared with the CaTiO3. The inset in (a) shows selected Bragg’s peak between 21.0 and 23.5°. (b) Rietveld fit of the XRD pattern of BaTiO3. The inset in (b) shows ball and stick molecular model for the unit cell of BaTiO3 perovskite, where Ba, Ti, and O are present in their atomic sizes.
We performed the Rietveld refinement of XRD pattern of BT using
The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) can be used to study the microstructure nature of the perovskite materials. We have recorded SEM micrographs of Nd0.4Sr0.6MnO3 manganite samples calcined at 800°C and 1200°C synthesized by auto-combustion method using FEI, Nova Nano SEM for the Nd0.4Sr0.6MnO3 perovskite and they are shown in \nFigure 7\n. The average values of the particle size were analyzed by ImageJ software and they are found to be 50 and 425 nm for the Nd0.4Sr0.6MnO3 perovskites calcined at 800°C and 1200°C, respectively. This clearly shows that the average particle size improves on increasing the calcination temperature. It confirms that the sample calcined at 800°C produces nanomaterial whereas that of at 1200°C gives bulk material.
\nSEM micrographs of Nd0.4Sr0.6MnO3 manganite calcined at (a) 800°C and (b) 1200°C temperatures.
\n\nFigure 8\n shows photoluminescence (PL) excitation and PL emission spectra of the Nd0.4Sr0.6MnO3 manganite calcined at 800°C and 1200°C. \nFigure 8(a)\n shows the excitation spectra of the Nd0.4Sr0.6MnO3 manganite in both the cases and contains an intense peak at 355 nm [45]. It was monitored at an emission wavelength of 646 nm. The intensity of bulk material is two times larger than the nanomaterial. When both the materials were excited with 355 nm they give strong red color at 646 nm as shown in \nFigure 8(b)\n. It also contains weak peaks at 483 and 582 nm. The emission intensity obtained in the case of bulk material is further two times larger than the nanomaterial. This is due to the increase in crystallinity and particles size of the materials. Thus, the calcination affects the morphology and optical properties of perovskites even though the perovskite material was synthesized by auto-combustion method.
\n(a) PL excitation and (b) PL emission spectra of the Nd0.4Sr0.6MnO3 manganite calcined at 800°C and 1200°C temperatures.
The perovskite materials are extensively studied by researchers due to their attractive properties. The perovskite materials have wide applications in various fields, which are listed below:
Photocatalytic activity; e.g., LaFeO3 [61].
Photovoltaic solar cells; e.g., LaVO3 [62].
Phosphor materials in photoluminescence; e.g., Ho3+/Yb3+/Mg2+ doped CaZrO3 [63].
Solid oxide fuel cells; e.g., Gd0.7Ca0.3Co1 − yMnyO3 [64].
Sensors and actuators; e.g., PbZrxTi1-xO3 [65].
Magnetic memory devices; e.g., Pt/La2Co0.8Mn1.2O6/Nb:SrTiO3 [66].
Magnetic field sensors; e.g., La0.67Sr0.33MnO3 and La0.67Ba0.33MnO3 [67].
Electric field effect devices; e.g., hetrostructure of Pb(Zr0.2Ti0.8)O3/La0.8Ca0.2MnO3 [68].
Ferroelectric and piezoelectric devices; e.g., BaTiO3, PbTiO3 [69].
Semiconducting electronic devices; e.g., La0.7Ca0.3MnO3\n
High dielectric constant; e.g., Bi1-xSrxMnO3 (x = 0.4, 0.5) [71].
High temperature superconductor; e.g., BaPb1-xBixO3 [72].
Hypothermia; e.g., La0.7Sr0.3MnO3 [73].
Supercapacitor; e.g., KNi0.8Co0.2F3 [74].
The lanthanide based perovskite phosphors are one of them and have unique photolumincence properties. The lanthanide ions are known for their narrow and sharp band emissions. They give emissions in the entire range of visible spectrum along with ultraviolet (UV) and near infrared (NIR) regions. These emissions are observed due to presence of meta-stable energy levels in the lanthanide ions. These levels have long lifetime and are responsible for very strong emissions. The lanthanide ions possess upconversion, downconversion, and quantum cutting phenomena. In upconversion, the two or more than two low energy photons are converted into high energy photons. When a high energy photon is converted into low energy photons it is termed as downconversion process. However, in quantun cutting, a high energy photon is converted into two low energy NIR photons. These processes lead numerous technological applications in different fields, such as red phosphors, light emitting diodes (LEDs), photonics, solar cells, tunable phosphors, temperature sensing, biological studies, drug kinetics, etc. [63, 75, 76, 77, 78, 79, 80, 81, 82]. \nFigure 9\n shows a block diagram for the lanthanide based perovskite phosphors, which shows their applications in various fields.
\nBlock diagram of the lanthanide based perovskite phosphor materials including their applications in various fields [
This chapter summarizes the basics of the perovskite structure, its stability and distortion. We have discussed the novelty of the perovskite materials, which accommodate different cations at A- and/or B-sites individually and/or simultaneously. We have also discussed various routes such as solid, liquid and gas-state synthesis for the preparation of perovskite materials mostly in the oxide powder forms. We have also briefly described the phase identification of the perovskites and their structural analysis using Rietveld refinement of the XRD data by taking an example of tetragonal BaTiO3 perovskite. The morphological and optical studies were also incorporated. We have also briefly listed various applications of perovskite materials including lanthanide based perovskite phosphors in various fields.
\nThe authors declare no conflict of interest in the chapter.
At the time this chapter is being written, the world is still experiencing the Severe Acute Respiratory Syndrome Coronavirus −2 (SARS-CoV-2)/COVID-19 pandemic. The dominant circulating strain of the virus has gone under multiple changes during the pandemic. The initial ancestral strain gave way to the alpha strain which gave way to the delta and omicron strain, which are currently the dominating circulating strains [1]. In addition, there have been emergence of other variants of interests (VOIs) or variants of concern (VOC) such as beta, gamma, P1, P2, lambda, and mu which could be a threat to international health security [1]. The emergence of these variants suggests virus adaptations to various determinants, responsible for the selection of these mutated variants.
This perspective chapter considers different biological determinants capable to contribute to viral mutations and thereby, emergence of new variants and the potential impact of this on the tools (vaccines and antibody therapy) against the SARS-CoV-2. However, it is important to note the determinants mentioned here may not be an exhaustive list of potential mechanisms to induce mutations. This chapter is based on theoretical and fundamental scientific concepts known to be involved from past outbreaks or current case reports from the ongoing pandemic. It is known that biological and environmental, among other determinants may drive viral mutations by different processes or mechanisms. Furthermore, by considering the roles these potential determinants may or already contribute to future SARS-CoV-2 variants we can improve global pandemic responses, saves lives, and contribute to the international health security.
A scoping literature review in search for current topics associated with SARS-CoV-2 or COVID-19 viral replication, adaptations, and biological determinants known to cause variant emergence (e.g., molecular factors, animal reservoirs, immunological factors, etc.) was conducted in biomedical databases such as PubMed, MEDLINE, and Google search engine. Additionally, World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and Food and Drug Administration (FDA) websites were relied upon to get the most recent information related to content of the chapter. Papers related to the biological determinants commonly associated with viral replication, recombination, adaptation, and immunological seletion were chosen based on the scope of the chapter. Biological determinants of variant emergence and their possible or current implications on the COVID-19 pandemic are presented below.
SARS-CoV-2, a beta coronavirus, is a RNA virus using an error-prone RNA-dependent RNA polymerase for replication [2]. The virus encodes a proofreading 3′ exonuclease (nsp140) but despite this activity, it accumulates genomic changes having a potential to create heterogenous mixture of antigenic proteins resulting in emergence of new variants [2]. The genomic mutation rate of SARS-CoV-2 in humans is estimated at 0.8–2.38 x 10−3 nucleotide substitutions per site per year with experimental data suggesting the virus capable of mutating and accumulating changes when it encounters new cell types [3, 4]. Thus, high viral load means high viral replication and thus higher potential for genomic errors due to replication. Along with the replication associated changes, dramatic changes in the virus phenotype can be observed due to genomic recombination in a cell infected with more than one coronavirus [2, 5]. Till now eight recombination events have been observed in SARS-CoV-2 but the frequency of such events is not known [6]. Random errors accumulated during replication/recombination along with population level natural and vaccine induced immunity, play an important role in Darwinian selection of these variants [2].
Although the exact precursor of SARS-CoV-2 is unknown, it is established it is of wild origin. The initial December 2019 outbreak in Wuhan, China was linked to the seafood and live animal city market [7]. This market was reported to trade poultry, snakes, hedgehogs, and other wild animals [8].
The different SARS-CoV-2 variants detected in animals including dogs, cats, tigers, lions, minks, and gorillas all had genomes related to the human variant yet had additional mutations. The presence and infection of these animal reservoirs with SARS-CoV-2 virus also increases the possibility of viral mutations/recombinations and emergence of variants. Zoonotic reservoirs capable of carrying and providing an environment for viral multiplication are listed below.
At the beginning of the pandemic bats were declared as the possible SARS-CoV-2 reservoir because of the genomic similarities with other coronaviruses infecting bats [9]. During the initial molecular epidemiological investigations, it was found the SARS-CoV-2 genome had similarities with coronaviruses isolated in
The fist isolated variant of SARS-CoV-2 was identified as pangolin-CoV because of similarities with coronaviruses isolated in the carcasses of Malayan pangolins
The virus has been detected in domestic cats and dogs [14]. Therefore, the transmission from humans to domestic animals is plausible. Specifically, the B.1.1.7 (Alpha) variant has been identified in domestic cats as well as in domestic dogs [19]. In contrast it appears that cattle, goats, and sheep are not infected by the virus [20].
Among animals kept in zoos the virus has been detected in gorillas, tigers, pumas, cougars, Asian small-clawed otters, and snow leopards. The genetic variability of SARS-CoV-2 is evident from the 9 genomes identified in tigers, lions, and their keepers [21]. The B.1.1.7 (Alpha) variant has been detected in gorillas, lions, leopards, and tigers [20, 22]. In another study the B.1.617.2 (Delta) variant was reported in Asiatic lions from India [23]. Farmed wild animals have been diagnosed with SARS-CoV-2. Specifically, SARS-CoV-2 has been identified in American minks (
Therefore, this possibility of emergence of new variants is ever present due to SARS-CoV-2 spread to different ecological environments and newer animal reservoirs resulting in a subsequent risk for spillover into humans and other species.
Lately, the phrase “Herd Immunity” is constantly brought up in news outlets, in commentaries, opinion pieces, and peer-reviewed articles. First introduced almost 100 years ago, it only recently gained popularity [24]. Although Herd Immunity is now a widely accepted concept, it may take on multiple meanings, each slightly different than the next. Some researchers consider Herd Immunity a threshold of the proportion of immune individuals that leads to a decline in infections or outbreaks [25, 26]. While others may use it to describe the proportion immune to a specific infection among a population or refer to it as a protective immunity pattern [25]. Herd Immunity is most referred to as the reduction of risk, of an infection, to susceptible individuals by the proximity and presence of immune individuals [25]. Herd Immunity may be used interchangeably as “indirect protection” or “herd effect”. Regardless of the definition variations, Herd Immunity leads to one outcome – the reduction of infection incidence. This concept, in conjunction with vaccines, has contributed to some of the most important public health achievements in the 20th and 21st century such as the smallpox eradication, polio elimination, and other vaccine-preventable diseases. This section explores the concepts behind Herd Immunity and current and future implications during the COVID-19 pandemic.
Topley and Wilson (1923) were the first to coin the term “Herd Immunity” and specifically look at host resistance in comparison with mass infection. After first mention of Herd Immunity, the term and overall concept started appearing and developing soon after [27, 28, 29]. Dudley [27] explored the idea of a “herd” or community and how it could be defined. He defined the idea of “infection pressure” (i.e., fundamental parasite factor) which may be determined by the infectious agent distribution frequency rates which is in the members of the herd [27]. He claimed, infectious pressure reacts with Herd Immunity, the increase of one increases the other and then decreases it to zero. This introduced the idea of needing a minimum amount of Herd Immunity, a threshold, in order to keep the infectious pressure at zero. Furthermore, he mentioned those two factors contributed to the type, quantity, infection speed (i.e., now known as R0) and the frequency and distribution of cases and their severity [27].
Yet Herd Immunity had one large limitation—to provide protection, a high proportion of the population must be immune to the pathogen. Before immunizations individuals had to survive and pass the pathogen to become immune; depending on the pathogen, likelihood of survival and being left with life-altering morbidities varied. However, as concepts behind Herd Immunity were evolving, vaccinations were becoming a staple of public health practice, allowing a large proportion of the population to be safely immunized against specific pathogens. Vaccination allowed for the fulfillment of Herd Immunity at a much faster rate and safer manner. This allowed for the concepts to be turned into mathematical possibilities.
Before vaccination and Herd Immunity there were two main hypotheses as to why outbreaks would end even though not all susceptible were affected: (1) the agent naturally loses virulence (2) the dynamics between susceptible, infected, and immune [26]. The later hypothesis, prevailed with its mathematical idea of “mass action principle” (MAP) [26]. This principle was based on a simple logical argument in favor of indirect protection given by Herd Immunity and became an epidemiological theoretical cornerstone. Eventually three theories converged into one general theory driving Herd Immunity: MAP, case reproduction rates (later called base reproductive rates [BRR]), and the Reed-Frost heterogenous population simulation approach [26]. The current formula used for Herd Immunity is H = 1–1/R0 = (R0–1)/R0, where R0 is the BRR. H is the Herd Immunity threshold, the proportion of immunes needed in order to reduce incidence and R0 is derived from the duration of contagiousness of an infected individual, the likelihood of infection per contact between a susceptible person and an infectious person or vector, and the contact rate [30]. The BRR serves as an indicator of the contagiousness of an infectious agent—the higher the R0, the more transmissible. An R0 > 1 indicates an outbreak will continue, while a R0 < 1 indicates the end of an outbreak, if R0 = 1 then the outbreak is stable [30]. In novel outbreaks, where everyone is susceptible the R0 defines the infectiousness of a pathogen. However, as individuals pass the infection or become immunized, the number of susceptible decreases and immune increases, and although this does not technically reduce the BRR, because the definition of R0 assumes a completely susceptible population, one can use the effective reproduction number (R) in lieu, which is similar to R0 but does not assume complete population susceptibility and, thus, can be estimated with populations with immune members [30]. Efforts aimed at reducing the number of susceptible persons through vaccination would result in a reduction of the R value, rather than R0 value.
Currently there are multiple vaccines approved internationally for human use and immunization campaigns are urging communities to get vaccinated, therefore reducing the number of susceptible in hopes to achieve herd immunity. However, there are multiple factors to consider in achieving herd immunity from the SARS-CoV-2 virus.
Originally, with an estimated BRR of 2–3, researchers estimated the proportion of the population needed to be immunized to induce Herd Immunity around 50–67% [31, 32, 33]. Since then, the emergence of new SARS-CoV-2 variants, most famously the Delta variant, studies suggest a higher BRR (>5) [34, 35] than the alpha variant (2–3) [31, 32, 33, 36, 37, 38, 39] increasing the vaccination/immune threshold needed in order to achieve a protective effect. An increase in the necessary number of individuals vaccinated propose additional hurdles in reaching Herd Immunity, with the ever-increasing anti-vax movement or individuals acting as “freeloaders” (i.e., individuals who are not vaccinated, yet expect to be protected by the rest of the community being vaccinated).
Secondly, future SARS-CoV-2 variants may mutate enough where the protection offered by the currently available vaccines or natural immunity may no longer suffice. The emergence of the Delta variant showed a reduced vaccine effectiveness compared to the previous variants, which the vaccines were developed from [40, 41]. While currently approved vaccines still provide significant protection from the Delta variant for reduced risk of infection and disease severity, the reduction in vaccine effectiveness is alarming. If emerging variants significantly or completely evade the protection offered by current vaccines or natural immunity, individuals may no longer fall under the immune proportion of the population. An example of this possible situation was reported in Manaus, Brazil, where by December 2020 the population was estimated to have naturally achieved the herd immunity threshold (i.e., before vaccinations were approved and available), estimated at 67%, yet experienced a wave of hospitalizations in January 2021 [42]. This case study further highlighted the limitations with calculating Herd Immunity. Possible reasons for the Manaus outbreak were an overestimation of the immune population, a possible waning immune response, mutants capable of evading responses from previous natural infection, and mutants may have higher transmissibility than previously circulating lineages [42]. Future scenarios where Herd Immunity may not be achievable or severely reduced would be staggering in relation to vaccination campaigns and reaching herd immunity—a grave threat to international health security.
All COVID-19 vaccines authorized or have received emergency use authorization (EUA) by FDA, EU/EEA, or WHO require a two-dose schedule except for the Janssen vaccines. All these vaccines require a period of 21 days to 12 weeks spacing between the primary and secondary dose [43]. In the early phase of the pandemic to reduce widespread community transmission, logistical issues, and shortages, many countries (e.g., UK, Canada) elected to delay the second dose in the population, thereby increasing the number of individuals with at least one dose. Policies such as the aforementioned in conjunction with waning of immunity after SARS-CoV-2 natural infection may result in large groups of people with only partial immunity against SARS-CoV-2 [43].
The Darwinian selection of variants with mutations for immune escape and its transmission in the community will depend on substantial selection pressure [44]. The greatest potential for the emergence of these immune escape mutations will be in those hosts with highest viral loads (increased mutations) while the greatest selection pressure will be in those with strongest immunological response [2, 44]. The level of immunological protection conferred after first dosage is dependent on the type of vaccine product in addition to the individual characteristics and variant [43]. In individuals with poor immunological response after first dose, there is potential for greater infection burden [44]. These individuals will have higher assumed rates of evolutionary adaptation because of higher viral load and replication. In those individuals with strong but partial immunological response, the infection rates would be lower but evolutionary selection pressure would be large, resulting in high rates of viral adaptations. Previous phylogenic research done on influenza viruses suggested the viral evolution and emergence of immune escape variants is maximum in those individuals with partial immunity (i.e., intermediate levels of selection and viral replication) [45]. Thus, having partially immunized individuals could lead to short-term benefits such as reduced peak of disease but in long term can result in higher infection burden and substantially higher risk of viral evolution to immune escape variants [44].
Several monoclonal antibodies were developed against the spike protein of SARS-CoV-2 to block the transmission of the virus inside the cells [46]. A single (Bamlanivimab) or combination monoclonal antibodies (Bamlanivimab/Etsevimab or Casirivimab/Imdevimab) received EUA for therapeutic management of SARS-CoV-2 and post-exposure prophylaxis [47, 48]. In theory, administration of monoclonal antibody therapy can alter the immunological selective pressure resulting in viral adaptation for the emergence of variants resistant to one or more monoclonal antibodies [49, 50]. This potential for the emergence of monoclonal antibody resistance has been observed in immunocompromised patients [51, 52, 53]. In trials for monoclonal antibodies, mutations resistant to antibodies were detected by next generation sequencing (NGS) assay in 10% of the patients receiving therapy with its transmissibility not determined [54]. Recently, a Wisconsin (WI) study using Bamlanivimab described the emergence of new resistant mutation E484K with further transmission to nearby contacts [55]. The emergence of variants with reduced susceptibility to neutralizing antibodies after polyclonal convalescent plasma therapy provides further proof of the effect of immunological selective pressure on emergence of new variants [49, 56]. It is conceivable, the widespread use of monoclonal or polyclonal antibody therapy may reduce barriers for the emergence of resistant variants to these antibodies which can further transmit to wider communities, potentially becoming a variant of concern. A widespread genomic surveillance is warranted to identify and control the spread of these antibody resistant variants [55].
During evaluation of the efficacy of vaccines, subjects with inhered or acquired immunodeficiencies are excluded from clinical trials. Therefore, there are limited information about the immunogenicity of SARS-CoV-2 vaccines among these patients. Field studies evaluating the effectiveness of COVID-19 vaccines demonstrate that immunocompromised subjects mount a lower antibody response when compared with immunocompetent subjects [57].
Viruses are highly sophisticated molecular machines that can go into an adaptive evolution in the human host establishing a latent reservoir, integrating into the human genome, or causing a chronic infection. Viruses such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus go into latent stage evading the host immune response while other viruses like Ebola can persist in immune sanctuaries [58]. Considering COVID-19 is an infection of pandemic proportions, it is plausible to think human host immune pressure can contribute to SARS-CoV-2 genetic diversity and selection with phenotypic changes [59]. Consequently, it is necessary to address the relationship between viral persistence in the immunosuppressed host. As a matter of fact, one of the hallmarks of SARS-CoV-2 is its capacity to co-opt various cellular factors and machineries damping the immune response [60]. Although not yet demonstrated, it is plausible to suggest SARS-CoV-2 may establish a latent infection or remain in immune sanctuary. However, SARS-CoV-2 persistence in the immunocompromised patient is well documented [61, 62], with viral persistence reported among cancer patients and transplant recipients [61, 63, 64, 65, 66, 67]. Viral coronavirus RNA has been detected up to ~60 days in cancer patients that developed respiratory symptoms. Moreover, the longest persistence of coronavirus RNA is recorded at 151 days in a patient with anti-phospholipid syndrome, which suggest these pathogens are of the opportunistic characteristic [68, 69, 70]. In the aforementioned patient, there were 31 substitutions and 3 deletions identified in the genome sequencies from the isolated agent. There were 12 mutations in the spike protein including 7 in the receptor-binding domain segment. Due to severe pulmonary complication the patient died [71]. Increased viral changes were also detected in another immunocompromised patient, whose disease prolonged for 101 days, where viral changes were limited during the first 60 days but increased after receiving plasma form a convalescent patient at days 63 and 65. Moreover, rapid shifts were observed in the spike area during the last days of the monitoring [71]. In another case-series, three patients receiving chimeric antigen receptor (CAR) T cells because of B-cell acute lymphocytic leukemia, showed multiple escape SARS-CoV-2 variants [71]. Consequently, like SARS-CoV-2 longer persistence in immunosuppressed patients, immunosusceptible elderly patients may also harbor the virus for prolonged periods compared to immunocompetent patients. Gaspar-Rodriguez et al. enunciated in 2021 that SARS-CoV-2 and other coronaviruses potentially establish a long-term, non-productive persistent infection in epithelial, myeloid, and neural host cells until viral clearance is achieved [62]. Prolonged COVID-19 in the immunosuppressed patient can be a determinant of the development of SARS-CoV-2 variants which can be spread among the general population [71]. This persistence of the virus in different types of immunosuppression are listed below.
Cancer patients are in immunodepression conditions because of the malignancy and oncological treatments like chemotherapy, radiotherapy, transplants, and immunotherapy. Patients with lung, blood, and bone marrow carcinomas are at a higher risk of harboring the virus for prolonged periods when compared with other cancer patients [72]. Patients with chronic lymphocytic leukemia (CLL) have shown inadequate levels of antibodies as well as cellular immune response [73]. These inadequate immune responses in CLL patients correlates with severe and prolonged forms of COVID-19 and has been supported by late conversion to negative PCR monitoring tests and longer hospitalizations [74]. The impaired humoral and cellular immune response in the CLL patients make these patients long term shedders of SARS-CoV-2 until infection is passed. One case study showed a COVID-19 positive CLL patient having persistent positive PCR test for 105 days after diagnosis [63]. Moreover, during this period a continuous variability in predominant viral variants was observed [63]. This delay in viral clearance in COVID-19 patients has been observed in patients receiving intravenous immunoglobulins as well as in those with hypertension [75].
Organ transplant recipients are patients with long-lasting immunosuppression; therefore, organ transplant recipients have been declared subjects with high risk for severe COVID-19. When COVID-19 positive liver transplant patients were compared with COVID-19 immunocompetent patients, the transplant recipients showed lower prevalence of antibodies against SARS-CoV-2, as well as a faster antibody decline [57]. Regarding viral shedding, immunocompetent asymptomatic COVID-19 infection subjects experience a faster viral clearance when compared with symptomatic individuals [76]. Kidney transplant patients with immunosuppression showed a longer shedding of the virus, of more than 28 days, which was correlated with a prolongation of symptoms [77].
It is demonstrated SARS-CoV-2 causes highest mortality among elderly populations. Also, viral shedding is increased, enhancing the spread of the virus as it was observed in the increased transmission in nursing homes. An explanation for these complications may be due to the elderly immune system being less competent than in young populations. In the elderly, it appears the production of cytokine and T-cells production worsen the inflammation process especially among those with comorbidities [78]. The increased shedding of SARS-CoV-2 is associated with a more severe clinical presentation and higher viral load peaks [79, 80, 81]. The delayed viral clearance in elderly patients’ airways can be explained by a decreased respiratory muscle function and diminished mucociliary function [79, 82].
Although corticosteroid therapy is being used to ameliorate the inflammation process, the use of corticosteroids at an early stage can suppress the immune cells which can prolong the clearance of the virus as well as its shedding. In a randomized study in the patients without respiratory failure, the methylprednisolone group showed a median viral shedding of 10 days vs. 6 days in the control group [83].
The molecular mechanisms of viral replication, multiple animal reservoirs, and immunological selection methods have the possibility for viral evolution to immune escape variants (Figure 1). Such epidemiological and evolutionary mechanisms are already seen in the emergence of different VOC worldwide [44].
Biological determinants of emergence of SARS-CoV-2 variants. An infection of SARS-CoV-2 in humans results in viral replication. In born errors of viral replication or genomic recombination can result in viral mutations. People with natural/artificial immunity will neutralize the non-mutated virus but has non-neutralizing immune response against mutated variant. Mutated SARS-CoV-2 thus undergoes this immunological selection for emergence of SARS-CoV-2 variant. Infection in animals with different host cell machinery led to mutated SARS-CoV-2 with potential for species jump and spillover into humans and emergence of SARS-CoV-2 variant.
Since the beginning of the pandemic, VOC having selective advantage of more transmissibility and resistance to natural or vaccine induced immunity have been evolving and supplanting previously circulating strains [43, 84]. The emergence of these VOC affects the effectiveness of vaccines in both partially and fully immunized individuals [43]. In vitro studies demonstrated lower neutralization capacity against all VOC compared to ancestral strains [41, 85, 86]. Based on evidence available for all vaccine types, partially immunized individuals have a lower degree of protection against symptomatic infection, moderate disease, and probable transmission with Delta VOC than Alpha VOC. In general, the vaccine effectiveness for all variants against symptomatic disease was much lower than those reported against severe diseases. The fully immunized individuals confer nearly equivalent protection for all outcomes against Alpha to that of Delta variants [43]. Table 1 summarizes the results of vaccine effectiveness by type of vaccine, outcome, and VOC.
Variant | Original | Original | Alpha | Beta | Gamma | Delta | Delta |
---|---|---|---|---|---|---|---|
Vaccine | SI | SD | SI | SI | SI | SI | SD |
Comirnaty (Pfizer/BioNTech) | 95% | 100% | 89.5% | 75% | 61% | 87.9% | 96% |
SpikeVax (Moderna) | 94.1% | 100% | ↓ Ant Neu | ↓ Ant Neu | ↓ Ant Neu | ↓ Ant Neu | |
Vaxzeria (AstraZeneca) | 70.4% | 81.3% | 66.1% | 10.4% | ↓ Ant Neu | 59.8% | 92% |
Johnson & Johnson | 74.2% | 85.4% | 64% | ↓ Ant Neu | |||
Cansino | 90–95% | ||||||
Sputnik V | 91.6% | 100% | No difference | ↓ Ant Neu | |||
Sinovac | 78.1% | 100% | ↓ Ant Neu | ↓ Ant Neu | ↓ Ant Neu | ||
Soberana (Cuba) | 62% |
Vaccine effectiveness of two dose of vaccines against symptomatic infection and severe disease caused by non-VOCs, alpha, and Delta VOCs.
SI, symptomatic disease; SD, Severe disease.
The emergence of new vaccine-resistant variants may necessitate the development of modified vaccines based on new sequences to prevent the prolonged circulation of vaccine-resistant variants [84]. It is important to conduct studies of these modified vaccines to determine its efficacy in developing a neutralizing immunological response against vaccine-resistant variants. This research is important despite the deployment of these newer vaccines not required until there is evidence of failure of current vaccines. Once the modified vaccines are introduced the molecular and immunological determinants of viral adaptation will necessitate to repeat the cycle of monitoring for even newer variants that might require further modifications in the antigenic sequence in vaccines.
Like vaccines, the viral adaptations seen against the monoclonal antibody therapy can complicate the deployment of these treatments at large scale in the general population [55]. The initial widespread use of Bamlanivimab as a single therapy and later removal due to epidemiologic trend further provides evidence for judicious use of monoclonal antibody therapy [87]. The usage of cocktail of antibodies should in theory reduce the probability of random selection of resistant variants however it does not totally remove this possibility [55]. This combined with monoclonal antibodies not preventing transmission, not providing immediate cure, lacking durable immunity, and potentially leading to antibody strains with some cross-resistance against vaccine or natural-acquired immunity suggests the need for caution before widespread usage of monoclonal antibody therapy [41, 55]. Increasing the scale of surveillance for mutations along with research into monoclonal antibodies against newer antigens should be adopted if the scale of use of monoclonal antibody has to be expanded [55].
Thus, the determinants of emergence of SARS-CoV-2 variants necessitates the inclusion of epidemiological, evolutionary, clinical, animal, and in vitro data related to changing antigenic sequences, vaccine and monoclonal antibody efficacy in the decision making of which antigens to be included in vaccines or targeted for therapy [84]. Lastly, it is important to recognize the limitations of the concepts presented in this chapter. This is a prospective chapter piece using concepts and theoretical ideologies commonly attributed to variant emergence. The inclusion of the determinants presented are a combination of expert knowledge on behalf of the authors and a scoping literature review conducted on SARS-CoV-2 and its current variants, therefore, this chapter is not meant to replace a systematic review.
This chapter presents theoretical and current determinants for variant emergence, specifically for SAR-CoV-2. The emergence of different VOC through the evolutionary cycle of the SARS-CoV-2 virus during the current pandemic (2019- ongoing) makes it important to understand the biological determinants of new emerging variants. The inherent errors in viral replication in humans and animal reservoirs combined with immunological selective pressure result in the Darwinian selection of variants of SARS-CoV-2 with potential for higher transmissibility and resistance to vaccine-based immunity or monoclonal antibodies. The different types of vaccines and associated immune response, partial immunization, waning of immunity, and heterogenicity in worldwide immunity results in wide differences in immunological selective pressure based on regions and virus evolutions. The global inequality in vaccine distribution further complicates this immunological selection pressure. The epidemiological and evolutionary cycle can result in viral adaptations with potential for selection of variants with higher transmissibility and immune escape properties. The emergence of these dangerous new variants can influence vaccine and antibody therapy effectiveness necessitating modifications in antigenic sequences used in production. This emergence of novel variants thus is a concern for international health security with a potential for furthering the COVID-19 pandemic and its associated negative health, economic, and social effects.
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\\n\\n\\n\\nThe Internet has changed the dynamics of scholarly communication and publishing which is why we find it necessary to clearly indicate our stance on what we consider to be a published scientific work. A significant number of working papers, early drafts, and similar works in progress are shared openly online between members of the scientific community. It has become common practice for researchers to announce their work on a personal website or a blog in order to gather comments and suggestions from other researchers. Such works and online postings are ‘published’ in the sense that they are made publicly available, but this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
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All published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
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\n\n\n\nIntechOpen is committed to disseminating high-quality scientific research in a manner that exemplifies the best practice in scholarly publishing. IntechOpen is an official member of the Committee on Publication Ethics (COPE), which advocates the maintenance of the highest ethical standards for all parties involved in the act of publishing, including Authors, Academic Editors of the book, Peer Reviewers, the publisher and Societies, where applicable.
\n\nIn line with publication ethics practices recommended by COPE, ICMJE, and other similar organizations, IntechOpen's contributing Authors, Academic Editors, and Peer Reviewers are required to declare fully all possible conflicts of interest.
\n\n\n\nIntechOpen's Authorship Policy is based on ICMJE criteria for authorship. In order to be identified as an Author, the following requirements must be met:
\n\nAll scientific works are subject to Peer Review prior to publishing. IntechOpen is a member of the Committee on Publication Ethics (COPE) and all participating referees and Academic Editors are expected to review submitted scientific works in line with the COPE Ethical Guidelines for Peer Reviewers where applicable.
\n\n\n\nThe Internet has changed the dynamics of scholarly communication and publishing which is why we find it necessary to clearly indicate our stance on what we consider to be a published scientific work. A significant number of working papers, early drafts, and similar works in progress are shared openly online between members of the scientific community. It has become common practice for researchers to announce their work on a personal website or a blog in order to gather comments and suggestions from other researchers. Such works and online postings are ‘published’ in the sense that they are made publicly available, but this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\n\n\n\nTo identify instances of fraud and misconduct during the publishing process, IntechOpen implements a robust policy governing such occurrences. In line with our general commitment to openness, and in order to maintain the highest scientific standards, we are committed to transparency about our editorial policy regarding retractions and corrections.
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\n\nIntechOpen publishes books in the English language. If you are interested in the translation of Book Chapters, please check IntechOpen's Translation Policy.
\n\n\n\nIn line with the Principles of Transparency and Best Practice in Scholarly Publishing, you can access a more detailed description of IntechOpen's Advertising Policy.
\n\n\n\nAt IntechOpen we realize that exceptional circumstances can occur, resulting in a request for a refund. We will honor all justified requests in the specific instances outlined in our Refund Policy.
\n\n\n\nAll chapters will be published via IntechOpen's 'Online First' service meaning chapters will be published individually, immediately after review and before the entire book is ready for publication, allowing content to be shared, searched and cited straightaway, thereby generating early stage interest and momentum for your research
\n\nOnline First Chapters are considered published on the day they are posted and are citable from that date.
\n\nChapters will remain listed as Online First until the final versions of the books are published online. Following publication of the full monograph, Chapters will be redirected from the Online First version and will be available only through the final link of the official published page.
\n\nYou are invited to download, use, reproduce, make derivative works of, display, distribute and cite the Online First works. You can find "How to Cite and Reference" by following the link at the end of each online book chapter. Please be aware that it is possible that further editing and changes might be made before the final release of the book.
\n\nIf there are supplemental materials to the chapter, these will be published at the time the final book is published online.
\n\nReaders and Authors can notify us if they find any errors in the works published under Online First. All major errors will be accompanied by a separate correction notice, erratum or corrigendum (Retraction and Correction Policy.)
\n\nIntechOpen books are available online by accessing all published content on a chapter level.
\n\n\n\nIntechOpen publishes different types of publications.
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At the beginning of humification, the significant decrease in the intensity of the band located at 1735 cm–1 shows that lignin is affected at the first stage of the composting process. At the end of the humification, the band located toward 3450–3420 cm–1 at the beginning of the process undergoes a systematic shift (Δν of the order of 10 cm–1) toward lower wave numbers. The band located at 1660–1650 cm–1 on the Fourier transform infrared spectroscopy (FTIR) spectra before composting shifts systematically toward 1640 cm–1 at the end of humification. This phenomenon can be used as index of compost maturity. 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Soil is a non-renewable natural resources on which the whole human society is dependent for various goods and services. The intensive, and unsustainable anthropogenic practices along with the rapid growth of the human population have led to continuous expansion and concern for the degradation of soil. The agricultural soil is exposed to a plethora of contaminants, the most significant contaminant among them is heavy metals. The major sources of heavy metal contamination are associated with agriculture, industries, and mining. The increase of heavy metal contents in the soil system affects all organisms via biomagnification. In this chapter, we will review various conventional and contemporary physical or chemical and biological techniques for remediation of contaminated soil. 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PAHs are considered hazardous because of cytotoxic, mutagenic, and carcinogenic effects. Sixteen individual PAH compounds have been identified as priority pollutants by the United States Environmental Protection Agency (U.S. EPA). All substances originated in to the environment by either biogenic or anthropogenic sources. Anthropogenic compounds describe synthetic compounds, and compound classes as well as elements and naturally occurring chemical entities which are mobilized by man’s activities. In the marine environment, the fate of pollutants is largely determined by biogeochemical process. Some of these chemical changes enhance the toxicity of the pollutants. Other chemical changes cause the degradation or immobilization of pollutants and, as a result, act to purify the waters. Possible fates for PAHs, released into the environment, include volatilization, photo-oxidation, chemical oxidation, bioaccumulation and adsorption on soil particles, leaching, and microbial degradation. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. 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His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. 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He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. 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He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. 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He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. 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