Resistivity and dielectric constants for typical near-surface materials (data from Ref. [13]).
\r\n\tEnvironmental applications will deal with water, and wastewater treatments, characterization of different sorbents, and waste removers, contaminants detection in water, and waste management.
\r\n\tIndustrial applications will focus on the analysis of paint, paper, pharmaceutical, and sugar industries and the applicability of infrared spectroscopy in these fields.
\r\n\tDrug analysis, food and dietary supplements testing and analysis, and natural products analysis will be discussed as parts of the pharmaceutical applications of infrared spectroscopy.
\r\n\r\n\tIn addition, the book will limp to the important applications of infrared spectroscopy in chemical and biological analyses. While the topics mentioned herein ( including the basics of IR, as well as the environmental and the industrial applications, food, and drug analysis) will be the major topics of this book, other applications and topics related to infrared spectroscopy are also invited.
",isbn:"978-1-80356-282-7",printIsbn:"978-1-80356-281-0",pdfIsbn:"978-1-80356-283-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"a72c83e454be85c1663d16ee18525862",bookSignature:"Dr. Marwa S. El-Azazy, Dr. Khalid Al-Saad and Dr. Ahmed El-Shafie",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11564.jpg",keywords:"IR Instrumentation, Sampling Modes, Spectral Analysis, Frequencies and Identification, Environmental Applications, Paint Industry, Paper Industry, Pharmaceutical Industry, Sugar Industry, Drug Analysis, Food Testing and Analysis, Natural Products Analysis",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 11th 2022",dateEndSecondStepPublish:"April 15th 2022",dateEndThirdStepPublish:"June 14th 2022",dateEndFourthStepPublish:"September 2nd 2022",dateEndFifthStepPublish:"November 1st 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Analytical Chemist, experienced educator, and researcher in water and wastewater treatment with more than 20 years of teaching experience at several institutions. Dr. Marwa has a track record of quality research inputs including more than 45 refereed papers in prestigious international journals, several conference presentations, and two book chapters, in addition to several research grants.",coeditorOneBiosketch:"Analytical chemist, experienced educator, and researcher with more than 20 years of teaching experience at Qatar University. Prof. Khalid Al-Saad is interested in environmental and biological application developments of spectroscopy and mass spectrometry.",coeditorTwoBiosketch:"Inorganic chemist and researcher from Qatar University, interested in wastewater treatment using green adsorbents.",coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"198210",title:"Dr.",name:"Marwa",middleName:"S.",surname:"El-Azazy",slug:"marwa-el-azazy",fullName:"Marwa El-Azazy",profilePictureURL:"https://mts.intechopen.com/storage/users/198210/images/system/198210.png",biography:"Dr. Marwa El-Azazy is an Analytical Chemist , experienced educator and researcher with more than 20 years of teaching experience at several institutions. Dr. Marwa’s main research interest is construction of sensors (using microfluidic platforms for point-of-care-testing of drugs and bio-analytes and ion-selective electrodes), chemometrics and analytical method development, spectroscopic analyses of drugs and pharmaceuticals, synthesis and characterization of nanomaterials, and development of green chemistry approaches for wastewater treatment. Dr. Marwa has a track record of research inputs including ˃45 refereed papers in prestigious international journals, several conference presentations, two book chapters, in addition to several research grants. She serves as a reviewer for a variety of international journals.",institutionString:"College of Arts and Sciences, Qatar University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],coeditorOne:{id:"256716",title:"Dr.",name:"Khalid",middleName:null,surname:"Al-Saad",slug:"khalid-al-saad",fullName:"Khalid Al-Saad",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRWwAQAW/Profile_Picture_1638452091614",biography:"Prof. Khalid Al-Saad is an Analytical Chemist , experienced educator and researcher with more than 20 years of teaching experience at QU. Dr. Khalid’s main research interest is applications and methodology development of spectroscopy, chromatography and mass spectrometry for the environmental and biological analysis. In addition, he worked in water treatments Dr. Khalid has a track record of research inputs including ˃40 refereed papers in international journals, several conference presentations, one book chapters, in addition to several research grants.",institutionString:"Qatar University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Qatar University",institutionURL:null,country:{name:"Qatar"}}},coeditorTwo:{id:"256946",title:"Dr.",name:"Ahmed",middleName:null,surname:"El-Shafie",slug:"ahmed-el-shafie",fullName:"Ahmed El-Shafie",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRWzmQAG/Profile_Picture_1638542333775",biography:"Dr. Ahmed El-Shafie is a Chemist, and he has more than ten years of experience in teaching and research. His research is mainly in inorganic and analytical chemistry, including spectrophotometric and fluorometric analysis of different drugs using the experimental design. Besides, synthesis of Nano-sorbents and their application in removing heavy metals, dyes, and pharmaceutically active materials from wastewater. Finally, he has published 16-refereed papers in a peer reviewed international journals.",institutionString:"Qatar University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Qatar University",institutionURL:null,country:{name:"Qatar"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"184402",firstName:"Romina",lastName:"Rovan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/184402/images/4747_n.jpg",email:"romina.r@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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\nGroundwater is defined as fresh water (from rain, melting of ice and snow) that soaks into the soil and is stored between pore-spaces, fractures and joints found in within rocks and other geological formations. Groundwater occurs in various geological formations, the ability of geological formations to store water is a function of its textural arrangement. The source of groundwater most times could be linked to surface run-off and infiltration of rainwater into the subsurface and streams from which it leads to the establishment of the water table and serve as a primary supplier of streams, springs lakes, bays and oceans. The textural arrangement (uniformly or tightly arranged texture, loosely arranged texture) found within most geological formations and rocks have a strong role to play in
An
Aquifer formation (as adapted from
Aquifers must not only be permeable but must also be porous and are found to include rock types such as sandstones, conglomerates, fractured limestone and unconsolidated sand, gravels and fractured volcanic rocks (columnar basalts). While some aquifers have high porosity and low permeability others have high porosity and high productivity. Those with high porosity and low permeability are referred to as poor aquifers and include rocks or geological formation such as granites and schist while those with high porosity and high permeability are regarded as excellent aquifers and include rocks like fractured volcanic rocks.
\nAquifers are generally been classed into two main categories namely confined aquifer and unconfined aquifers.
\nConfined Aquifers are those bodies of water found accumulating in a permeable rock and are been enclosed by two impermeable rock layers or rock bodies. Confined Aquifers are aquifers that are found to be overlain by a confining rock layer or rock bodies, often made up of clay which might offer some form of protection from surface contamination. The geological barriers which are non-permeable and found exist between the aquifer causes the water within it to be under pressure which is comparatively more than the atmospheric pressure. The presence of fractures, or cracks in bedrocks is also capable of bearing water in large openings within bedrocks dissolving some of the rock and accounts for high yields of well in karst terrain counties like Augusta, Bath within Virginia. Groundwater flow through aquifers is either vertically or horizontally at rates often influenced by gravity and geological formations in these areas.
\nConfined aquifers could also be referred to as “Artesian aquifers” which could be found most above the base of confined rock layers. Punctured wells deriving their sources from artesian aquifers have fluctuation in their water levels due more to pressure change than quantity of stored water. The punctured well serve more as conduits for water transmission from replenishing areas to natural or artificial final points. In terms of storativity, confined aquifers (Figure 2) have very low storativity values of 0.01 to 0.0001.
\nSchematic cross-section of aquifer types (source:
Unconfined Aquifer unlike confined aquifers are generally found located near the land surface and have no layers of clay (or other impermeable geologic material) above the water table although they are found lying relatively above impermeable clay rock layers. The uppermost boundary of groundwater within the unconfined aquifer is the water table, the groundwater in an unconfined aquifer is more vulnerable to contamination from surface pollution as compared to that in confined aquifers this been so due to easy groundwater infiltration by land pollutants. Fluctuation in the level of groundwater varies and depends on the stored up groundwater in the space of the aquifer which in turn affects the rise or fall of water levels in wells that derive their source from aquifers. Unconfined aquifers have a storative value greater than 0.01. “Perched aquifers” (Figure 3) are special cases of unconfined aquifers occurring in situation where groundwater bodies are separated from their main groundwater source by relatively impermeable rock layers of small areal extents and zones of aeration above the main body of groundwater The quantity of water found available in this type of aquifer is usually minute and available for short periods of time.
\nSchematic cross-section of aquifer types (source: coloradogeologicalsurvey.org>wateratlas).
Petro-physical properties of aquifers are properties that help in the defining and characterizing aquifers. Some of the properties considered are:
\nHydraulic Conductivity could be described as the relative ease with which a fluids (groundwater) flows through a medium (in this case a geological formation or rock) which is quite different from intrinsic permeability in that though it describes the water-transmitting property of the medium it is however not influenced by the temperature, pressure or the fluid passing through the geological formation. Hydraulic conductivity of a soil or rock or geological formation depends on a variety of physical factors amongst which includes porosity, particle size and distribution, arrangement of particles and other factors.
\nMathematically hydraulic conductivity could be defined by the formula below:
\nwhere K is the hydraulic conductivity (cm/s or m/s), k is the intrinsic permeability, \n
Generally, for unconsolidated porous media, hydraulic conductivity varies with particle size as such clayey materials exhibits low values of hydraulic conductivity as compared to sands and gravels that exhibits high values of hydraulic conductivity (150 m/day for coarse gravels, 45 m/day for coarse sand and 0.08 m/day for clay). This is so because the small particle size arrangements (fine grained) in geological formations contained mainly of clayey materials though porous is not permeable enough to allow groundwater flow within it however in sands and gravels (medium to coarse grained) we have medium to coarse arrangement of particle sizes which results to a porous and permeable geological formations or rocks that allows a higher ease of groundwater flow. It is however essential to point out that we could have geological formations or rock that exhibit medium values of hydraulic conductivity, this is in the case where you have a geological formation made up of moderate amounts of clayey material and sandy materials. It should also be noted that variations in hydraulic conductivity values of geological formations or rocks is dependent on factors such as weathering, fracturing, solution channels and depth of burial.
\nPorosity of a geological formation or rock or soil could be described as the measure of the contained voids or interstices expressed as a ratio of the volume of voids to the total volume. It could also be defined as the volume of pores within a rock or soil sample divided by the total volume of the rock matrix (pores and solid materials contained with the rock). When a rock is emplaced by either cooling from an igneous melt or induration from loose sediment or soil formation from weathering of rock materials, it possess an inherent porosity known as primary porosity which reduces with time by actions of cementation or compaction. However, when joints, fissures, fractures or solution cavities formed within rocks after the must have been emplaced it is referred to as secondary porosity. Therefore, total porosity is the sum of primary and secondary porosities.
\nIf all the pores found contained in a rock are not connected, then only a certain fraction of the pores would allow for water movement. The fraction that allows for water movement is known as the effective porosity example of which includes pumice, glassy volcanic rock (solidified froth) probably would float in water because its total porosity is high and it contains much entrained gas.
\nPorosity of a rock is determined to a large extent by the packing arrangement of particle sizes and the uniformity of its grain-size distribution. As such a cubic packing (Figure 4A) would give a porosity of 47.65%, the greatest and most ideal a rock with uniform spherical grains can achieve as the centers of eight such grains from vertices of a cube. However, if the packing arrangement of the rock where to change to be that of a rhombohedral (Figure 4B) then, its porosity would reduce to 25.85% as the centers of the eight adjacent spheres form the vertices of rhombus.
\n(A) Cubic packing (B) Rhombohedral packing.
Mathematically porosity (
where
Transmissivity (T) more simply could be defined as the property of aquifer to transmit water. It could also be defined as the amount of water that can be transmitted horizontally through an aquifer unit by full saturated thickness of the aquifer under a hydraulic gradient of 1 or as the rate at which water of prevailing kinematic viscosity is transmitted through a unit width of aquifer under a unit gradient.
\nIt could be mathematically defined as:
\nwhere
Aquifers are characterized by petro-physical properties such as
In geophysical investigations using electrical techniques, two primary properties of interest been considered are electrical conductivity or dielectric constant.
\nElectrical techniques make involves
Schematic geological section and associated resistivity and velocity contrasts at interfaces (from Burger [
Electrical resistivity (ER) is more frequently been used as compared to other electrical techniques in groundwater investigations of which includes the characterization of aquifers. Electrical Resistivity (ER) involves the introduction of time – varying direct current (DC) or very low frequency (<1 Hz) current into the ground between two current electrodes to generate potential differences as measured at the surface with units of Ohm-meters (Ω-m). A deviation from the norm in the pattern of potential differences expected from homogeneous proffer the necessary information on the form and electrical properties of subsurface inhomogeneities.
\nA typical Electrical Resistivity (ER) investigation made up of a 2 – electrode system would include 2 – current electrodes and 2 – potential electrodes. As current is been injected into the ground, corresponding potential differences (∆
The expression in Eq. (4) for a homogeneous ground is also the same applied for heterogeneous ground; however the general term “apparent resistivity (ρa)” is substituted for resistivity (ρ) in Eq. (4). Apparent resistivity (ρa) is used here rather than the actual resistivity of the subsurface due to the non-homogeneity nature of the subsurface.
\nA four – electrode configurations is been used most commonly when it comes to measuring apparent resistivity of the subsurface. The simplest of these configurations is the Wenner configuration (Figure 6a) where the outer two current electrodes C1 and C2, apply a constant current, and the inner two potential electrodes, labeled P1 and P2, measures voltage difference created by this current. The electrode spacing has a fixed value a, and the apparent resistivity of the subsurface sampled by this array could be computed using the equation:
\nCommon electrode configuration used to measure apparent resistivity of the subsurface C1 and C2 are the current electrodes and P1 and P2 are the potential electrodes. (a) Wenner Array (b) Schlumberger array (c) dipole – Dipole array. (from Burger [
Asides the Wenner array mode of electrode configuration, another commonly used electrode configuration is the Schlumberger array (Figure 6b), where the spacing (MN) between the potential electrodes (P1, P2) is much smaller as compared to the spacing (2 L) between the current electrodes (C1, C2).
\nThe electrode configuration in (Figure 6) represents that of a dipole – dipole array where the potential electrode pair and current electrode is closely spaced, however there exist significant distances between the two sets of electrodes (Figure 6c) Unlike the cases of the Wenner and Schlumberger arrays, where data collected through either profiling or sounding mode depends a lot on the electrode array geometry.
\nTo illustrate, we consider the Wenner array. Profiling involves the lateral movement of the entire array along the surface at fixed distances to obtain apparent resistivity measurements as a function of distance. The values of the measurements are assigned to the geometric center of the electrode array. Interpretation of measurements is usually with its data aimed at location of geological structures buried stream channels, aquifers or water bearing formations etc.
\nSounding unlike profiling involves gradual and progressively expansion of expansion of the array about a fixed central point with current and potential electrodes being maintained at a relative spacing with depth been a function of electrode spacing and subsurface resistivity contrasts(Figure 7a–c). The dashed lines representing current flow lines in an homogeneous environment while bold lines represents actual current flow in single interface that separates units with different resistivities. Next we look how electrode spacing, current and its’ influence on depth of penetration. In Figure 7a, when the electrode spacing is close, it is observed that the current only upper interface (i.e. the interface of lower resistivity). The scenario in Figure 7b is different; as electrode spacing has increased resulting in greater penetration depth and higher apparent resistivity values due to the influence of the lower (higher resistivity) layer. Lastly when the electrodes are farther apart, only substantial current amounts are found to flow through the resistivity layer (Figure 7c).
\nEffects of electrode spacing and presence of an interface on apparent resistivity measurements. The dashed lines represent current flow lines in the absence of the interface and the solid lines represent actual current flow lines (a–c) as the current electrode spacing is increased, the current lines penetrate deeper and the apparent resistivity measurements are influenced by the lower (more resistive) layer. (d) the qualitative variations in apparent resistivity as a function of electrode spacing are illustrated by the two-layer sounding curve (from Burger [
The curve (Figure 7d) reveals qualitative variations in apparent resistivities which increases with electrode spacing, a, this curve is known as a sounding curve revealing geology of the subsurface with resistivity increasing with depth provided geology is homogeneous. However in the case where the geology is inhomogeneous it results in a complex sounding curve whose interpretation is non-unique. To interpret electrical resistivity sounding data, various curve-fitting or computer inversion schemes are used or measured and compared with model computations [1]. A classic example where both modes of data acquisition (profiling and sounding) is been used is in the location of a buried stream channel (Figures 8a and 6a) using Wenner array. The contour map (Figure 8a) produced from resistivity measurements of several profiles collected near San Jose, CA, using an a-spacing (Figure 6a) of 6.1 [1, 2] reveals contours of equal apparent resistivity delineating an approximately east–west trending high apparent resistivity values. To understand the cause of high apparent resistivity values here, a geological cross-section (BA) was drawn across the map. The geological cross-section (BA) drawn is based on four expanding – spread traverses (soundings), apparent resistivity profile information and information from three boreholes whose locations are indicated on the cross-section. The critical observation of the cross-section shows that the area with high-resistivity as on the apparent resistivity map (Figure 8b) is a zone of gravels and boulders that defines the location of a buried stream channel (subsurface structure).
\nResistivity survey used to delineate lateral and vertical variations in subsurface stratigraphy. (a) Contour map produced from resistivity measurements, (b) a geologic cross-section (BA) revealing high-resistivity trend in a zone of gravel and boulders that define the location of a buried stream channel (from Ref. [
Aside the mapping of subsurface structure and stratigraphy, electrical resistivity measurements could be channeled towards the inferring lithological information and hydrogeological parameters needed for the mapping groundwater. For groundwater mapping, electrical conduction (inverse of electrical resistivity) is considered. Here the interest is the delineation of connected pore spaces, void spaces, interstices, fractures within rocks that are water filled which leads to a reduced resistivity values and high conductivity. However more information is still needed as high conductivity within rock formation or units could be due to a number of things asides water some of which includes presence of clay minerals, contamination plumes etc.
\nCommon earth materials have wide range of electrical resistivity values revealed in Table 1, however some of these values are known to overlap for different earth materials. Values commonly vary over 12 orders of magnitude and have a maximum range of 24 orders of magnitude [3]. The following statements as regarding electrical resistivity holds;
Resistivity is sensitive to moisture content; thus unsaturated sediments usually have higher resistivity values than saturated sediments.
Sandy materials generally have higher resistivity values than clayey materials
Granitic bedrock generally has a higher resistivity value than saturated sediments and frequently offers a large apparent resistivity contrast when overlain by these sediments.
Resistivity and dielectric constants for typical near-surface materials (data from Ref. [13]).
Asides the use of sounding curves, empirical formulae have also been adapted in relating measurement of apparent resistivity with hydrological parameters of interest as this relates to aquifers. The empirical formula developed in the laboratory by Archie [4] relates these parameters:
\nwhere \n
And n, a, and m are constants {n ≈ 2, 0.6 ≤ a ≤ 1.0, and 1.4 ≤ m ≤ 2.2; Ward [5]}. Though Archie’s law was formulated using lithified materials, Jackson et al. [6] posited its’ accurate usability for unconsolidated materials also. The equation presented by Eq. (6) is used generally for well log interpretation however if \n
In conclusion, it could be said that the complexities that exist in the interpretation of sounding curves and the non-unique solution it gives, suggests the suitability of surface resistivity in determined subsurface geology. Also due to its sensitivity to parameters like moisture content it’s been termed a useful tool in hydrological investigations as reviewed by Ward [5], Van Nostrand and Cook [8].
\nElectromagnetic (EM) techniques as tool for geophysical exploration has dramatically increased in recent years served as a useful tool for groundwater and environmental site assessment. It involves the propagation of continuous-wave or transient electromagnetic fields in and over the earth through resulting in the generation of time-varying magnetic field. For any of such surveys to be carried out three components are essential; a transmitters, receivers, buried conductors or conductive subsurface. These three form a trio of electric-circuit coupled by an EM induction with currents been introduced into the ground directly or through inductive means by the transmitters.
\nThe Primary field travels from the transmitter coil to the receiver coil via paths above and below the surface. Where a homogenous subsurface is detected no difference is observed between the fields propagated above, below and within the surface other than a slight reduction in amplitude. However, the interaction of the
It’s paramount to recall that electrical conductivity is an inverse of electrical resistivity; as such electrical conductivity measurements made using electromagnetic methods is also dependent on subsurface texture, porosity, presence of clay minerals, moisture content and the electrical resistivity of the pore fluid presence. The acquisition of EM data requires less time, achieving greater depth of investigation than resistivity techniques. However, the equipment used are expensive and the methods used to qualitatively interpret data from EM surveys is complicated than those used in resistivity methods. This is because a conductive subsurface environment is essential to set up a secondary field measured with inductive EM methods (Figure 9). Electromagnetic methods as a tool for geophysical investigation and exploration is most suited for the detection of water—bearing formation (aquifers) and high – conductive subsurface target such as salt water saturated sediments.
\nElectromagnetic induction technique (from Ref. [
Instrumentation could take in varying forms; but mainly consist of a source and receiver or receiver units. The source (transmitter) transmits time-varying magnetic fields with the receiver measuring components of the total (primary and secondary) field, magnetic field, sometimes the electric field and the necessary electronic circuitry to process, store and display signals [9, 10]. Data obtained from electromagnetic surveys, like their resistivity counterpart can be collected in profile and sounding mode with their information been presented as maps or pseudo-section to give a better picture of the subsurface. Acquisition, resolution and depth of investigation from this survey are been governed by mostly by conditions of the subsurface and domain of measurement.
\nEM surveys are divided into two domain system of measurement namely; frequency and time domain system. For frequency domain EM systems, we have the transmitter classed as either high or low frequency transmitters; high transmitter frequencies permits high- resolution investigation of subsurface conductors at near-surface or shallow depths while lower transmitter frequencies allows for deeper depth of investigation at the expense of resolution. This implies that high frequency EM surveys yield better result for near-surface due to high resolution, however if interested in deeper subsurface investigation (low frequency EM surveys) then we have need a way around the low resolution. In the case of time domain system, secondary magnetic field is measured as a function of time, with early – time measurement being suited best for near-surface information while late- time measurement yields results of the deeper subsurface. It is paramount to note that depth of penetration or investigation and resolution is also been governed by coil configuration; while measurements from coil separations are influenced by electrical properties thus the larger coil separation investigates greater depths while smaller coil separation investigates near-surface.
\nBecause Electrical Conductivity is related inversely to Electrical Resistivity, as such discussions relating electrical resistivity to lithology or hydrological properties can be applied in an inverse manner to measurements involving electrical conductivity. Electrical conductivity for example is higher for
Ground Penetrating Radar (GPR) as a geophysical technique is relative new and becoming increasingly popular critically understanding the events of the near-surface or shallow subsurface. Davis and Annan [13] viewed the Ground Penetrating Radar (GPR) as a technique of imaging the subsurface at high resolution using electromagnetic waves transmitted at frequencies between 10 to 1000 MHz. GPR could also be viewed as a non-destructive geophysical technique due to its successful geological applications in urban and sensitive environments. Some of these applications include the subsurface mapping of water table soils and rocks structures (e.g. groundwater channels) at high resolutions. It is similar in principle to seismic reflection profiling in however, propagation of radar waves through the subsurface is controlled by electrical properties at high frequencies.
\nThe GPR survey system is made up of three vital components; a
Flow chart for a typical GPR system (after [
Processing of the radargram could be simplified by processing operations such as dewowing (removal of low frequency components), Gain Control (strengthen weaker events), deconvolution (restores shape of downgoing wave train such that primary events could be recognized more easily), Migration (useful in removing diffraction hyperbolae and restoring dips). The resultant radargram when correlated with the subsurface geology shows varying interfaces, geological structures that might be present (Figure 11a and b). Though GPR has successfully been utilized in unsaturated (non-electrically conductive or highly resistive) and saturated (electrically conductive) environment [14], however performance is higher in unsaturated (non-conductive) than in saturated (conductive) such as non-expanding clay environment such as at Savannah River Site in South Carolina [15].
\n(A) Interpretation of a GPR profile image (B) interpretation of the prominent stratigraphic units, structures and faults.
The depth of penetration or investigation of GPR survey is function of the frequency of the EM waves or radar waves and nature of the subsurface material been investigated as shown in Figure 12 for varying subsurface materials at frequencies ranging between 1 and 500 MHz. If the nature of subsurface material is highly resistive and has low conductivity then we expect a higher depth of penetration however for subsurface materials that are less resistivity and very conductive we expect low depth of penetration. Depth of penetration asides from been dependent on nature of the subsurface material (i.e. resistivity or conductivity nature) is also a function of frequencies which in turn affects resolution of subsurface imagery or radargram. Thus at low frequencies, we expect a greater depth of penetration at the expense of resolution while at high frequencies, we achieve a lower depth of penetration at higher resolution.
\nThe relationship between probing distance and frequency for different materials (after Cook 1975).
Ground Penetrating Radar (GPR) data have been successful utilized in the hydrogeological investigations to locate the water table and to delineate shallow, unconsolidated aquifers [16].
\nThe use of Seismic techniques in subsurface characterization is based on the propagation of elastic waves generated from a seismic controlled source, propagated through the subsurface, boreholes, received by receivers (geophones or hydrophones) and displayed on seismographs (as a combination of waves velocities and attenuation). From these, properties of the subsurface like porosity, hydraulic conductivity, elastic moduli and water saturation which could help us better understand the subsurface could be derived.
\nSubsurface investigation involving Seismic techniques are categorized into three; Seismic Refraction, Cross-hole transmission (tomography) and Seismic Reflection.
\nWith Seismic Refraction, the incident ray is refracted along the target boundary before returning to the surface (Figure 13). The arrival times gotten from the refracted energy are displayed as function of distance from the source with their interpretation been made manually using simple software or forward modeling techniques. The relationship between arrival times and distances could be used to obtain velocity information directly. Seismic Refraction techniques are the most appropriate for a few shallow (50 m) targets of interest, or where one is interested in identifying gross lateral velocity variations or changes in interface dip [17]. Though Seismic Refraction yields lower resolution than Seismic Reflection and Seismic Cross-hole tomographic, it is however chosen over Reflection as they are inexpensive and help to determining the depth to the water table (buried refractor) and to the top of bedrock, the gross velocity structure, or for locating significant faults. The buried refractor is usually saturated and has a greater velocity than the unsaturated equivalent soil unit and the bedrock surface [18].
\nMajor ray paths of P-wave energy (from Burger [
Cross-hole transmission (tomography) data acquisition is possible using several techniques amongst which includes seismic techniques, electrical resistivity, electromagnetic, radar with seismic being the most common. Majority of cross – hole tomographic seismic data have been collected for research however the those collected over extremely high resolution of up to 0.5 m are better suited for site characterization. Figure 14 shows a typical example of seismic cross-hole survey. The multiple sampling of the intra-wellbore area permits very detailed estimation of the velocity structure [19]. As seismic P-wave velocities can be related to lithological and hydrogeological parameters as discussed above, this extremely high resolution method is ideal for detailed stratigraphic and hydraulic characterization of interwell areas [20].
\nCross-hole tomography geometry for seismic and radar methods. Sources and receivers are located in separated boreholes, and energy from each source is received by all geophones. Cross-holes acquisition geometries have also been used with electrical resistivity and EM methods.
In conclusion, Aquifers could be classified into confined or unconfined aquifers on the basis of the presence or absence of the positioning of water table. Its characterization is a function of variations in subsurface petro-physical properties (porosity, hydraulic conductivities, and permeability) measured using geophysical techniques like electrical resistivity, electromagnetic induction, ground penetrating radar and Seismic techniques.
\nHaving considered, what aquifers are and their characterization based on petro-physical properties of the aquifers. It is also essential to note that these properties help in selecting suitable techniques for aquifer exploration, characterization and its exploitation. However the most widely used and suitable of these techniques is the electrical methods particularly use of the electrical resistivity technique because of its speed, reliability and the fact that it is more economical in terms of use for exploration and exploitation.
\nZika virus (ZIKV) is an arthropod-borne flavivirus, considered a reemerging infectious disease as well as a neglected tropical disease [1]. Moreover, ZIKV was also classified as sexually transmitted disease (STD), since viral RNA and infectious particles were detectable in reproductive organs and others described some cases related to sexual transmission [2, 3]. Although the major concern about ZIKV infection is the intrauterine transmission [4, 5, 6].
Innate immunity during pregnancy still needs attention when some infection compromises pregnancy success. Recently, the world testified a huge public health problem during Zika virus (ZIKV) outbreak in Latin American countries [7, 8, 9], in which poor outcomes were observed firstly in Brazilian newborns from mothers infected on early pregnancy phase (1st -2nd trimester) [7, 8]. Consequences of viral infections on newborns are irreversible and public health and social costs are immensurable [10], making World Health Organization consider Zika infection a public health emergency in 2016 February [11].
Due to its neurotropic features, the infection caused by ZIKV has been evidenced [12, 13, 14], which show a correlation between clinical manifestations based on its tropism by brain neuronal cells of fetuses and neonates born from infected pregnant women, with a strong association to neurological damage, including microcephaly and other fetal neurological disorders, collectively named as Congenital Zika Syndrome (CZS) or Zika Associated with Birth Defect (ZABD) [15, 16, 17, 18].
The immune system is composed of a set of flexible mechanisms that are fundamental to maintain homeostasis, allowing many interactions and coexistence between different populations of microorganisms and the host. The imbalance of homeostasis can be caused by a microorganism because of its pathogenic behavior. With the establishment of an active infection and consequent immune response, inflammatory mediators, produced initially, collaborate to activate cellular populations of the innate immunity, promoting antiviral and cytotoxic responses, for example. At first, these effector responses would influence the viremia resolution with the re-establishment of homeostasis. However, the loss or dysfunction of this immune response can generate a harmful environment that triggers an uncontrolled damage inflammation and consequent cell death due to a direct cytopathic effect caused by the microorganism [19].
Some studies were conducted to understand the mechanisms involved in vertical transmission. During pregnancy, the transfer of ZIKV to the placenta occurs after an infection of decidua, the placenta maternal region, since studies have shown that decidua cells are permissive to ZIKV infection and remain permissive throughout pregnancy [20, 21]. From the infection of the decidua, there are two routes by which ZIKV reaches the fetus: infection of syncytiotrophoblasts (SBTs) through capillaries containing maternal blood or infection of Extravilous Trophoblast (EVTs) by cell-to-cell propagation [4]. In vitro studies have shown that ZIKV can infect first-trimester cytotrophoblasts CTBs and EVTs [4, 20, 21]. On the other hand, STBs are high producers of type III interferon and remain relatively resistant to viral infection throughout pregnancy, therefore, the main route hypothesis for transplacental transmission of ZIKV is that of the spread of decidua to EVTs [21, 22]. Additionally, infection of placental macrophages, the Hofbauer cells by ZIKV may contribute to both intrauterine transmission and immunomodulation [23, 24]. Further, transplacental transfer of ZIKV is more likely to occur in the pro-inflammatory environment and tolerant to placental immunity in the first trimester.
Histopathological and immunological studies in placentas have shown that infections by ZIKV lead to an increase in important inflammation markers such as TNF, CCL5, and altered vascular permeability such as metalloproteinases [25]. In addition, in vitro experiments demonstrate that trophoblastic cells become progressively more resistant to infection by ZIKV during pregnancy, partly through the secretion of IFNs [26]. In this context, a lot of efforts were raised to provide funds to deeply investigate how to avoid another spread of Zika virus infection, as well as drugs tests and vaccine development based on viral proteins, DNA vaccines, Virus Like Particles (VLP), chimeric viruses, among other strategies [27, 28, 29, 30]. Therefore, there are few studies to investigate the pregnancy immunity and how the immune interface mother-to-child could contribute to infection spread with drastic consequences to fetus [21, 31, 32, 33, 34]. To our knowledge, the imbalance of normal pregnancy immunity is already cause of metabolic disorders and the poor outcome is related to abortion [35, 36, 37]. Then, a viral infection can make this picture worst and tragic [8, 13, 15, 38, 39].
Like other Flaviviruses, ZIKV life cycle modulates machinery and functions of target immune host cells, making essential virus-cells interactions for pathogenesis development. Moreover, while several human and animal models’ studies have argued and proved ZIKV neurotropism, there are still many answers regarding viral pathogenesis in mother and its influence the fetal neural system and persistence, and clinical outcome. In this chapter we will put together the information about innate immunity during gestation, highlighting three parts probably involved with clinical outcome: 1) interferon type III; 2) innate regulatory cells; and 3) cell death pathways modulation. Additionally, we will focus on discussing how the dynamic responses of innate immune system during pregnancy and its effects in newborns, could be modulated by ZIKV, as well as how efforts on development of new/old drugs and vaccines could be effective to help pregnancy success.
The success of pregnancy is dependent on a coordinated balance between the “invading” fetal trophoblast and a receptive maternal decidua in the placenta, maintaining a dynamic and responsive immune system. The longest period of the pregnancy, fetal growth, demands a symbiotic and tolerogenic environment, but congenital viral infections can disrupt this equilibrium. In order to avoid infection severity placenta actively modulates the immunologic profile of the maternal-fetal interface [40, 41]. In this context, recent studies demonstrated that placenta responds to ZIKV infection by production of the newest interferon group type III interferons [21, 42, 43].
Type III interferon (IFN-λ 1–4) comprising a group of cytokines with action pathways under strengthen discovery [44, 45, 46], basically acting with shared inflammatory regulation and antiviral properties [47]. IFN-λs receptor was identified as a complex composed of two subunits: IFN-λR1 and IL-10R2, which is also a receptor subunit of the regulatory cytokines IL10, IL22, and IL26 [48]. In contrast with the classical pro-inflammatory type I interferons which receptors are expressed in almost all cell types, the IFNLR1/IL10RB complex is expressed primarily in cells of epithelial origin and few immune cells conferring selective IFN-λ responsiveness to them: neutrophils [49], myeloid dendritic cells (DCs) [50, 51] and plasmacytoid dendritic cells (pDC) [52]. Because of the restricted cell types producing IFN-λs, this cytokine acts locally as an immunologic barrier in organs with suppressing innate pro-inflammatory responses and limiting host damaging effects associated with inflammation [53]. Moreover, IFN-λs utilize mechanisms to suppress viral infections which induce a strong antiviral state following receptor binding with non-translational and translational processes [49, 54].
Between the different inflammatory regulation actions already described for IFN-λs, the suppression of neutrophil gains prominence because they are the immune cells that present higher expression.
of IFN-λR1 at the steady-state [55, 56, 57]. Neutrophils contribute to various stages of the reproductive process since conception and implantation, ensuring fetal wellbeing during pregnancy and finally contributing to parturition and postpartum maternal health. On the other hand, aberrant neutrophil activity is associated with severe pregnancy-related disorders such as pre-eclampsia, recurrent fetal loss or gestational diabetes mellitus [58, 59, 60]. In murine models, it was demonstrated that neutrophil exposed to IFN-λ can induce antiviral interferon-stimulated genes (ISGs); and IFN-λ (but not IFN-β) specifically activated a translation-independent signaling pathway that diminished the production of reactive oxygen species and degranulation in neutrophils, which might permit a controlled development of the inflammatory process [49].
Studies utilizing a cellular model of collagen-induced arthritis demonstrated that IFN-λ2 was protective and could stop the progression of the disease, diminishing infiltration of neutrophils to the inflamed joints as well as the production of IL-1β upon treatment with pegylated recombinant IFN-λ2 [57].
IFN-λ is strongly associated with DCs activity inducing an effector adaptive immunity response [63, 64]. Studies with a mice model of influenza A virus infection demonstrated that IFN-λ directed acts in the migration and function of CD103(+) dendritic cells, also regulating DC IL-10 network [65]. Migratory CD103(+) DCs derived from skin, lung, and intestine, efficiently present exogenous antigens in their corresponding draining lymph nodes to specific CD8(+) T cells through a mechanism known as cross-presentation, demonstrating the IFN-λ importance for the development of specific CD8+ T cell responses [65, 66]. Moreover, IFN-λ contributes to the formation of tolerogenic DCs cell, contributing to control inflammatory responses and homeostasis by fostering the conversion of naive T cells into induced Foxp3(+) regulatory T cells [66]. In vitro studies demonstrated that IFN- λ directs DCs to a regulatory phenotype with diminished capacity to stimulate T cell proliferation in a PD-1/PD-L1 dependent manner with contribution from the imbalanced cytokine milieu, such as low IL-12 and IL-2 and/or high IL-10 production [50]. Another study using mixed lymphocyte cultures demonstrated that IFN- λ -treated DCs specifically induced IL-2-dependent proliferation of a CD4(+) CD25(+) Foxp3(+) T-cell subset with contact-dependent suppressive activity on T-cell proliferation initiated by fully mature DCs [51].
Plasmacytoid dendritic cells (pDC) are rare cells found in peripheral blood and lymphoid tissues, considered to be “professional” type I IFN-producing cells and produce 10- to 100-fold more IFN-α than other cell types in response to enveloped viruses. However, in vitro IFN-λ treatment of pDC resulted in increased virus-induced expression of both IFN-α and IFN-λ, indicating that pDC are high producers of IFN-λ1 and -λ2 in response to viral stimulation and the consequences of this high IFN-λ production by pDC should be further explored [52].
In human congenital ZIKV infections, it was demonstrated that ZIKV infection leads to a typical inflammatory response in the placenta, including the expression of anti-viral Type I interferon genes (
Summary of Interferon lambda (IFN-λ) function during normal pregnancy (A), Healthy Congenital Zika infection (B), and Zika-Associated Birth Defects (C). (A) In normal pregnancy, trophoblasts exhibit a constitutive IFN-λ production, contributing to the general tolerogenic environment demanded by pregnancy (A1); Considering the peripheral blood tissue IFN-λ Interact with: (A2) neutrophils leading to a decrease in ROS and IL1β, and (A3) migratory CD103+Dendritic cells (DC) that present low levels of PD1, IL2 and IL12 together with high IL10. These CD103+DC foster the conversion of naive T cells into induced Foxp3(+) regulatory T cells (Treg) (A4). In the placenta, the constitutive IFN-λ is accompanied by decreased type I IFN pathway: low expression of IFIT5, IFNA, and IFNB, and high expression of type I IFN the negative regulator ISG15 (A5). In the lack of viral infection, the interferon regulatory factors IRF7 and IRF9 present low expression levels (A7). (B) In healthy congenital Zika infections, the placenta expresses high levels of IFN-λ to protect the fetus from congenital defects (B1). In this low damage antiviral response, high levels of IFN-λ elicits the production of ISGs and the decrease of ROS and IL1β by circulating neutrophils (B2), meanwhile the CD103+ DC presents an accented regulatory profile (B3), with induction of high specific anti-ZIKV response by Treg (B4) and TCD8+ cells (B5). In the placental level type, I interferon pathway shows a slight increase, together with the enhance of IRF7 and IRF9, forming a balanced antiviral response. (C) In Congenital Zika Syndrome (CZS) the lack of IFN-λ contributes to a damaging outcome (C1). Diminished levels of IFN-λ could not control the neutrophil activity, culminating in augmented ROS and IL1β (C2), and presence of aberrant activation forms as well as degranulation, migration, and NETosis (C3). Without IFN-λ the Dendritic Cells (DC) present a prό-inflammatory profile, with augmented PD1, IL2, and IL12 and diminished IL10 (C4). The placenta shows an exacerbated type I interferon response, which together with low IFN-λ levels (C5), leads to an imbalanced damaging antiviral response. Grey arrows represent the production or expression levels (up = high, down = low). Double arrows represent a high magnitude of production or expression. Red dashed arrows represent the direction of function/induction events that have been known and those suggested. Figure created using Biorender software (
Immunity during pregnancy is very important to be explored since successful pregnancy requires that immunoregulatory mechanisms are triggered to suppress activated fetal-specific T cells lymphocytes [36, 37]. Maternal immune cells can recognize paternal antigens on fetus. Thus, it has been very well described that dysfunction of immune cells during pregnancy can lead to immunologic fetal rejection by mother, in which the consequences are related to abortion, preterm delivery, or other severe complications [35, 36, 37].
Then, maternal-fetal tolerance involves the regulation of mother’s immune system to tolerate the semi allogeneic fetus expressing paternal antigens without immune rejection. Even though, some studies showed that regulatory T cells are the main cells which plays an important role in suppressing activated T cells during gestation; since then innate immunity system is poorly investigated [69, 70, 71].
Considering infections during pregnancy, it is also important to know that changes on maternal immune responses are required to induce limited immunosuppression without loss of host defense, in which a balance between activated and immunosuppressed cells needs to be regular [35].
Myeloid-derived suppressor cells (MDSC) are a heterogeneous mixture of immature myeloid cells, been part of innate immune cells, having a crucial role in immunomodulatory mechanisms during pregnancy [36, 72, 73]. There are two subtypes of MDSC, a monocytic and granulocytic. Phenotype is characterized by expression of CD33 and CD11b in humans, CD14 by monocytic MDSC and CD15 by granulocytic MDSC cells but lacks the maturation marker HLA-DR. But both subtypes share the characteristic of immune-suppressive function inhibiting activated NK and T cell expansion [73, 74].
Normally, immature myeloid cells as MDSC are scarcely found in peripheral blood, and their maturation includes macrophages, dendritic cells, and granulocytes formation. Nevertheless, the MDSC are also recognized by their role in some pathological conditions, like cancer, sepsis, stress, autoimmune disorders and infectious diseases [38, 75, 76].
Several studies have been reported that a decrease of MDSC during pregnancy may lead to poor outcomes, as miscarriage [77]. Also, it has been shown that progesterone levels increase MDSC during pregnancy in mice, as well as high levels of TNF and IL-1β, pro-inflammatory cytokines [38, 78].
In murine models, it was demonstrated that MDSC can produce TGF-β and IL-10, as immunosuppressive cytokines, similarly to regulatory T cells. Adding to that, MDSC can suppress T cell activation and function by arginase-1 (Arg-1) secretion, as well as nitric oxide synthase and indoleamine 2,3 dioxygenase aimed to deplete nutrients for T cell proliferation, as I-arginine (I-Arg). According to Ismail 2018, arginine is also involved in replication, and virulence of several agents, as viruses and bacteria. Then, it is suggested that an accumulation of MDSC in placenta could influence an increase of arginase activity, and it would serve for a dual purpose, inhibiting the adaptive immune system whilst also providing potential protection against infection by arginine auxotrophic pathogens [79].
Nitric oxide (NO) has been related to embryo successful implantation during early pregnancy, but excessive NO production by decidual macrophages seems to be harmful and was linked with early pregnancy loss [37, 80, 81]. Another study suggests that in early pregnancy in decidua CD33+ cells express nitric oxide synthase, playing an important role to maintained pregnancy during this phase, while in later pregnancy CD33+ cells lose the expression of this enzyme [35, 37].
Kostlin-Gille
Regarding Zika virus, there are few studies showing the presence of MDSC on women blood and during pregnancy, and considering the facts, it will be very important to know any relationship of their presence with congenital syndrome, as observed in 2016, Brazil [82, 83]. A study with 10 non-pregnant women with Zika infection showed that frequencies of circulating MDSC did not change over time [84]. Another study with pregnant monkeys infected with Zika virus showed that an imbalance on blood frequencies of MDSC and activated CD8 T cells in the acute phase may lead to poor outcome to the fetus. Adding to that, the high frequency of MDSC on placenta from pregnant monkeys showed a positive effect on pregnancy outcome, even more if a drug antiviral treatment was used [85].
Furthermore, it is worth to note that immune signature, sometimes is the key factor to explain some diseases progressions. Despite Dengue viruses is more related to signals and symptoms with Zika virus infection [86, 87], some similarities with hepatitis C virus (HCV) were also noted, and mechanisms of immune evasion have been described, as inhibition of interferon pathway, allowing virus life cycle for a long-term period, up to 100 days [88, 89]. To note, ZIKV infection is also classified as an immune-mediated viral disease, like Dengue and other viruses [86, 87, 90]. Disease progression in HCV patients to chronic infection has been associated to an increase of MDSC phenotype in peripheral blood mediated by viral proteins [38]. Wang et al., 2017 examined Japanese encephalitis virus (JEV) infection leading acute encephalopathy depending on suppression of adaptive immune response, especially T follicular helper cells, mediated by enhanced MDSC populations, such as an involvement of MDSC on splenic B cells reduction, and in lower levels of total IgM JEV-specific neutralizing antibodies in mice models [39]. Burrack et al., also suggests that MDSC has an important suppressive T cells activity and may contribute to reduce the immune-mediated disease during Chikungunya infection [90].
Otherwise, the immunosuppressive activity triggered by RNA viruses, MDSC has been associated with metabolic regulation of immunopathology induced by DNA viruses, like hepatitis B virus (HBV) [91]. Pallett et al., 2015 showed that frequencies of MDSC on liver from HBV patients without liver damage, monitored by levels of liver transaminase enzymes, were higher in comparison with patients with liver damage, showing a protective effect for patients with immune-mediated viral disease, as hepatitis B [91].
In the new coronavirus pandemic (COVID-19), the MDSC have been reported to play an important role in the early phase of symptoms, increasing their frequency on blood in the first days of signals and symptoms, and it was related to poor outcome in severe acute respiratory syndrome in hospitalized patients. Pregnancy is a risk factor for COVID-19 severity, given the Brazilian high mortality rate of 12.7% in June 2020 withing pregnant, which may be associated with the change of the immunity [92, 93, 94].
Although few studies involving MDSC frequencies on blood during Zika infection were published yet, those cell type needs to be investigated, even though in animal models for medical science breakthroughs. The technique to characterize this cell phenotype is simpler than to characterize regulatory T cells, once the procedure does not require intracellular staining [95].
If those MDSC are crucial to maintaining a healthy pregnancy, any adverse effects, as Zika virus infection could trigger an imbalance between MDSC and T cells. This dysfunction may induce a deactivation of functional MDSC on blood and placenta with failure to attempt to eliminate viral infection. In addition, T cell function during ZIKV infection is known to be delayed throughout interferences on interferon pathway, as described above. Then, this scenario may contribute to immune evasion of ZIKV, in which viral replication on maternal-fetal environment is unavoidable, inducing poor outcomes during pregnancy: fetal death, congenital syndrome, abortion, neurological disorders, etc. (Figure 2).
Myeloid-derived suppressor cell (MDSC) activation and regulation triggered by normal pregnancy and by Zika virus infection. Summary of MDSC functionality during normal pregnancy (A) and during acute phase of Zika virus infection (B) as suggested by others into an innate immunity dysregulation observed in abnormal pregnancies on monkeys [
It has been described that a protective response by innate immune cells to viruses is triggered by several distinct mechanisms including apoptosis, necrosis, paraptosis, pyroptosis, autophagy cell death, and others. Each one is depending on several aspects of infection, including where the microorganism was detected, susceptible target-cells, through signaling systems discharging the death signal, and its intensity. During the innate immune response to infections, programmed cell death may occur as a direct pathogenic mechanism of viral spread and escape from the immune system or represents an appropriate host response to limit pathogen replication. Apoptosis of lymphocytes and monocytes also plays an important role in the control of inflammatory responses, as well as in the development of maternal-fetal tolerance [96, 97, 98, 99].
Type 1 programmed cell death, also known as apoptosis, is defined by internucleosomal DNA fragmentation, marked irreversible apoptotic characteristic indicating chromatin condensation, degradation of cytoskeleton and nuclear proteins, protein crosslinking, apoptotic bodies’ formation baring ligands for receptors of phagocytic cells and, finally, the uptake by these phagocytes [97, 98, 99]. Type 2, or autophagic cell death, presents unique characteristics organelles formation including autophagosomes and autophagolysosomes in the dying cell, sources of self-degradation, and recycling [100].
Two pathways can regulate the apoptosis program in different aspects: extrinsic and intrinsic. Extrinsic pathway is activated by a transduction signal through death receptors, in which TNF, Fas ligand, or TRAIL bind to their respective receptors, such as TNF receptor family: TNFR1, Fas (CD95/APO-1) and TRAIL-R1/2. A complex signal mediated by this binding leads to an enzymatic cascade of cell degradation, and at this point caspase-3 is activated promoting DNA damage [101]. Intrinsic pathway involves intracellular mitochondria, which its membrane is the local for many Bcl-2 family members and their activity in inducing / inhibiting the mitochondrial apoptosis program implies in those proteins lead to membrane collapse as well as a transition from mitochondrial permeability promoting apoptosis process [96, 101, 102, 103, 104, 105].
Taking together, type 2, or autophagic cell death, consists of a conserved catabolic process that contributes to degradation and recycling of many intracellular substances, through lysosome activity. In this sense, many studies have shown its importance in immune responses, including degradation of microbes, direct viral peptides MHC class I presentation [106] and even altering T-cell signaling and tolerance [107, 108]. At first, autophagy is necessary to keep the cell alive under stress conditions that precede their demise. Such kind of cell death could be achieved by several mechanisms, including prolonged hypoxia or digestion of vital factors, regulatory molecules or essential organelles. In a stress situation, caused by virus, an infected cell can induce intracellular signals of autophagy, inhibiting cell proliferation, arresting cell cycle and eventually leading to cell death [106, 107, 108, 109, 110, 111].
In the acute ZIKV infection during pregnancy, macrophages and dendritic cells are involved in inflammatory cytokines production, in which CARD9 expression, an important regulator of caspase activity playing an important role in cell apoptosis regulation, is elevated allowing that pattern recognition receptors (PRR) induce pro-inflammatory cytokines cascade, as the first step on CZS, as suggested [67]. According to Quicke et al., Hofbauer cells infected with ZIKV in placenta induces IFN type I activation, reactive oxygen species production, as well as pro-inflammatory cytokines, but with minimal cell death, showing a scape of innate immune response [23]. Recently, Cao et al., showed that ZIKV could activate and increase an autophagic process in pregnant mice, suggesting an imbalance of trophoblastic cells in placenta, and relation with fetal loss [112]. Corroborating, Ribeiro et al. using a human model of placenta explants for in vitro infection demonstrated tissue injury as consequence of the association between fetal pro-inflammatory responses mediated by IL-1β, IL-6 and TNF and extrinsic caspase 3 dependent apoptosis (TNF-TNFR pathway). Together data suggest that ZIKV infection corroborates to placenta innate immune and hormonal dysfunction, increasing loss barrier integrity [42]Thus, this inflammatory status could trigger cell death and barrier loss, allowing ZIKV cross placenta and infect fetuses’ neural stem cells (Figure 3) [23, 113, 114, 115]. Interesting, autophagosomes are present in neural stem cells and it could facilitate ZIKV replication [116], although inflammation generated as well as the cytopathic effect itself culminate in extensive caspase-dependent neuronal cell death.
Programmed cell death activation during normal pregnancy and abnormal pregnancy induced by Zika virus. Normal pregnancy equilibrium is driven by regulation of number of innate immune cells in placenta leading by programmed cell death. In this situation, caspase activity starts on CARD9 expression with cytokines production by Hofbauer cells (1.A), which oxide nitric (NO) regulates trophoblasts autophagy (2.A, 3.A). Products of Hofbauer cells activity in the surveillance in placental parenchyma contributing to extrinsic (Fas/Fas-L) and intrinsic pathway (BCL2/BAX) activation in fetus brain with low expression of pro-inflammatory cytokines, regulating number of neural stem cells and microglia by apoptosis (4.A), maintaining the healthy pregnancy. Acute ZIKV infection during pregnancy suggests that macrophages and DCs are involved in pro-inflammatory cytokines production, in which CARD9 is upregulated, increasing caspase activity, allowing pro-inflammatory cytokines and reactive species cascade (1.B, 2.B), exacerbating autophagy in placenta (3.B). Taking together this innate immune dysfunction, fetus brain is affected by high activation of apoptosis pathway (4.B), provoking a cascade of cell death with an abrupt reduction of neural cells, causing severe damage [
Corroborating, Lum et al. has shown that ZIKV mainly infects fetal microglia and induces high levels of pro-inflammatory cytokines that could be harmful to the fetus [117]. In addition, the analysis of in vitro culture, fetal brain histology and
Thus, once in fetus central nervous system, ZIKV may contribute to extrinsic (Fas/Fas-L) and intrinsic (Bcl-2) pathways activation for programmed cell death, reducing number of neuronal cells. Thus, the risk of congenital syndrome is eminent, mainly in the first trimester, as well documented (Figure 3) [67, 118, 119, 120, 121, 122, 123]. Some studies with fetuses’ autopsies and infants with microcephaly have been demonstrated a broad spectrum of microscopic neuropathological abnormalities and brain damage, with direct virus cytopathic effects in neural glial cells. In this way, these data support the strong association with apoptotic cell death and microcalcifications [13, 23, 124].
In general, pregnancy is a challenge for prevention and control infectious diseases regard to a safe drug or vaccine development to do not disturb the innate/adaptive immunity homeostasis, however, there were no drugs approved for ZIKV infection treatment [28, 29, 30]. Here, drugs and vaccines candidates tested in animal models or in newborns will be described with details (Table 1).
Therapy | classification | Mechanism of action | Immune effect | Pregnancy safety | References |
---|---|---|---|---|---|
Peg Interferon-λ2 | Not approved | Antiviral immunobiological | Enhance IFNL-λ pathway activity | Yes/Mice models | Jagger et al., 2017 [26] |
Sofosbuvir | Category B/Approved for hepatitis C treatment | Direct-acting antiviral drugs | Not explored | Yes/Mice models | Mesci et al., 2018 [136] |
NITD008 | Not approved | Direct-acting antiviral drugs | Not explored | Yes/Mice models | Watanabe et al., 2019 [27] |
Hydroxycloroquine | Category C/Approved for malaria and autoimmune diseases therapy | Cell membrane interaction to induce cell death | Reduction of autophagy activity | Yes/Pregnant women | Cao et al., 2017 [112] |
rVSV vaccine | Not approved | Recombinant viral vector vaccine | Increases in CD8+/CD44high/IFN-γ + T cell populations on spleen | Yes/Mice models | Betancourt et al., 2017 [147] |
VRC5283 | Clinical trial phase II (VRC-ZKADNA090–00-VP) | DNA plasmid vaccine | Induce antigen-specific antibody production/ induce of CD8+ T cells response | Yes/Mice models | Richner et al.,2017 [155] |
mRNA-LNP vaccine | Clinical trial phase I (NCT03014089) | mRNA vaccine | Induce antigen-specific antibody production/ induce of CD8+ T cells response/Minimizes ADE | Yes/Mice models | Richner et al.,2017 [156] |
Therapeutic agents or vaccine candidates targeting virus or immunity with promisor potential to use during ZIKV infection in pregnant women.
Type III interferon has been emerging as an efficient and low damaging therapeutic agent not only directed for the virus but also for fungal and bacterial infections, as well as cancer, autoimmune, and vascular diseases [54]. The more restricted expression of IFNLR1 likely contributes to the improved safety profile of IFN-λl in clinical studies compared to type I IFN. Pegylated IFN-λ1 have already been tested in phase 2b clinical trial to chronic hepatitis C treatment and hepatitis B, associated with improved rates of virologic response with fewer extrahepatic adverse events compared to pegylated IFN-α [125]. Even though it was deemed less effective than alternative treatments for these infections, pegylated- IFN- λ can be potential candidate ready for deployment if new indications are identified [126]. There are other viral targets for IFN- λ therapy been tested in murine models: norovirus [127], and influenza virus [128], and west nile virus – last one is another member of Flaviviridae family. It is noteworthy the effect of IFN-λ on infection with west nile virus, an encephalitic flavivirus: Treatment of IFNLR1 knockout mice with pegylated IFN-λ2 resulted in decreased blood–brain barrier permeability, reducing west nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge [129].
The effectiveness and low damage treatments for other correlated viral infections, combined with the protagonist of IFN-λs as immunoregulatory and antiviral agent in ZIKV raise the idea of IFN-λs as ZIKV therapy, and some groups already achieve exciting good results. Concerning ZIKV infections, Jagger, et al., (2017) suggest that IFN-λ2 treatment could be a safe solution to minimize Congenital Zika Syndrome severe outcomes. Using a type III interferon-deficient mouse model, authors showed that these animals had an increase of ZIKV replication in the placenta under ZIKV infection, and treatment of pregnant mice with IFN-λ2 reduced ZIKV viremia [26]. Considering the vaginal epithelium as the first line of defense against sexually transmitted ZIKV, treatment of primary human vaginal and cervical epithelial cells lineages with IFN-λ induces host defense transcriptional signatures with augmented expression of ISGs (IFI44L, OASL, OAS1, and MX1) and inhibition of ZIKV replication. Female mice submitted to treatment with IFN-λ and intravaginal ZIKV transmission showed low levels of virus replication in the female reproductive tract with a hormonal stage-dependent role [130].
Some studies were driving to evaluate effects of independent direct-acting antiviral drugs on Zika virus infection (Table 1), as sofosbuvir, an FDA-approved nucleotide analog inhibitor of the hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) [131, 132]. In vitro and
There are few studies investigating innate immunity during antiviral therapy, especially when its concern to Flaviviridae family [38, 135, 138, 139]. Scarce literature revealed knowledge about antiviral therapy immune effects only during hepatitis C infection [138, 139]. Antiviral drugs, as pegylated interferon (PEG-IFN), ribavirin, and direct-acting antiviral agents (DAA) have been related with a reduction of innate regulatory cells, as MDSC, in peripheral blood from hepatitis C chronic patients, in which T cells were increased and immune function was reestablished [138, 139]. Nevertheless, all those drugs are aimed to interrupt viral replication and any dysregulation of immune cells during pregnancy is not safe, then those drugs are not recommended to be used during gestational period [140]. Besides no immune response evaluation was related to DAA therapy, it has been known that small molecules with specific activity should not induce any immune alterations in maternal-fetal immunity [140].
Safety and effectiveness of sofosbuvir on Zika virus infection should be addressed to immune response evaluation, which is poorly explored, even more in pregnant animal models. More studies and investments are needed for non-clinical and clinical studies, to get safety therapeutic protocols aimed to pregnant women with Zika virus or other flavivirus infection.
Genetic manipulation has been proven to be a promising tool for vaccine and therapy development. Considering the type 2 of programmed death, autophagy is activated by ZIKV in placental parenchyma and is involved in poor outcome during pregnancy, this cell death pathway has been a target for therapies [112, 141, 142, 143].
Recently, a study showed the role of an autophagy gene (Atg16I1) during ZIKV infection in pregnant mice model, in which inducing a deficiency in this gene limited ZIKV vertical transmission, as well fetal damage, improving placental and fetal outcomes [112]. In addition, an antiviral compound approved to be used by pregnant women for malaria and autoimmune diseases [141], hydroxychloroquine (HCQ), has been used to dampen autophagic activity
Based on the knowledge of ZIKV infection that can trigger a caspase-3 activation contributing to cell death of neural progenitor cells during pregnancy, it is an extremely relevant approaches targeting cell death pathways for antiviral treatments even though for therapeutic vaccines.
Recombinant viral vectors have been highlighted as therapeutic alternatives to prevent and treat infectious disease [144, 145], considering its specificity and the adverse effects of antiviral drugs and some vaccines [140, 146]. Betancourt et al., 2017 showed that a recombinant viral vector from vesicular stomatitis virus (rVSV) anti-ZIKV vaccine increased IFN-γ production by splenic CD8+ T cells as well as high neutralizing anti-ZIKV antibody titers from pregnant mice. This study also demonstrates that neonatal mouse from vaccinated dams was partially protected against neurological manifestations of ZIKV infection following wild-type virus challenge [147]. This rVSV using pre membrane and envelope region together obtained from a ZIKV strain as reference had the potential to protect from ZIKV infection during prenatal and neonatal development, likely through the transmission of maternal IgG. Despite rVSV vaccine induces IFN-γ production in pregnant mice, this vaccine needs to be evaluated for other types of interferon, mainly its effects on placental tissues .
mRNA vaccines as well as DNA-based vaccines represent a versatile vaccine platform and an alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration [148]. Recent technological advances have allowed mRNA vaccines to demonstrate encouraging results in both animal and human models. Regarding prophylactic mRNA vaccines, a number of reports have demonstrated the potency and versatility of mRNA to elicited protective immunity against a variety of infectious agents in animal models against, including influenza virus, Ebola virus, Zika virus, Human Immunodeficiency virus 1 (HIV-1), herpes simplex virus, cytomegalovirus, hepatitis C and respiratory syncytial virus [149, 150, 151]. It has been noted that approximately ten mRNA vaccines programs have entered clinical trials [152].
The importance of mRNA-based vaccines and therapies is emphasized when mRNA-based biopharmaceuticals are entering the market with guidance of new biopharmaceutical companies. Modern Therapeutics, an mRNA therapy company evaluated various mRNA vaccine technologies to identify immunogenic and scalable candidates. The pipeline of this company shows different investigative stages mRNA vaccines of the following vaccines Respiratory Syncytial virus (RSV), Cytomegalovirus (CMV), human metapneumovirus (hMPV) + Parainfluenza virus Type 3 (PIV3), Influenza A subtypes H10N8, and H7N9, Zika, and Chikungunya. Curevac is the first biopharmaceutical company that developed the first prophylactic mRNA vaccine in the clinics, recently they showed that RNActive® vaccines induced long-lived and protective immunity to influenza A virus infections in various animal models [153].
Thus, big pharmaceutic companies, such as Merck & Co., have been invested in Modern Therapeutics aiming to expand the field of mRNA vaccine (https://www.modernatx.com/). Indeed, nucleic acid vaccine platform has been presented to combat the emergence of acute viral diseases, mainly to rapidly contain emerging outbreaks before they spread out of control. In this context, two vaccines were developed to combat the ZIKV outbreak (1) DNA plasmid vaccine encoding the prM-E genes of ZIKV and (VRC5283) (2) mRNA vaccine (mRNA-LNP), both vaccines mediate protection from ZIKV infection in mouse models. The DNA plasmid vaccine is in phase 2 human clinical trials (VRC-ZKADNA090–00-VP) and vaccine mRNA-LNP is in phase 1 clinical trial (NCT03014089) [154, 155, 156].
Considering that vaccine trials might not be performed in pregnant women and have not yet tested vaccines against ZIKV vertical transmission, there is a need for establishing the efficacy of ZIKV vaccines against mother-to-child transmission in animal models. In order to address those questions, it has been shown that vaccination with DNA plasmid encoding Zika virus prM-E and a lipid-encapsulated mRNA vaccine-elicited antigen-specific antibody and CD8+ T cell responses in mice, being able to generate a high level of protection against vertical transmission. Moreover, the mRNA-LNP vaccine not only inhibited vertical transmission but also ensured that fetuses are protected therefore, reinforcing its potential as promising vaccine for pregnant women [155]. Since there are few studies in the field of ZIKV vaccine candidates that evaluated vertical transmission, intrinsic maternal factors as well as fetal health, nucleic acid vaccines are pointed as a great opportunity to contain ZIKV infection.
Considering the normal pregnancy, the innate immunity balance is conduct by downregulation of effector T cells and NK cells leading by innate regulatory cells (MDSC) and upregulation of pro-inflammatory cytokines. This innate immune modulation that occurs mainly at the placenta, includes interferon pathway and cell death modulation as shown in Figure 4A. Gestation has its own difficulties to successful outcomes regarding maternal immune tolerance. Zika virus infection becomes classified as disease-causing birth defects, developing an abnormal pregnancy, as consequence of immune dysregulation (Figure 4B). Thus, antiviral therapy is the key to control this immune imbalance showing positive effects in innate immunity on pregnant mice models. It has been known that efforts through vaccines development targeting pregnant women will be the solution for ZIKV prevention, as well as for other arboviral infections, to maintain immune homeostasis and generate healthy babies. Finally, this chapter brings some new thoughts that help for targeted improvements in medical science considering Zika infection on pregnancy, and innate immune system linked to therapies previewing the prevention and control.
Summary of innate immunity functionality during normal pregnancy and in Zika virus infection focus on interferon III, myeloid-derived suppressor cells, and programmed cell death activities. During pregnancy, initial signal is dependent on nidation process and placenta formation leading by trophoblasts expansion and activation. Following this process, innate cells, such as neutrophils, DCs, and cytokines are activated (1.A, 2.A) with IL10 and TGF-beta production in periphery, allowing immunosuppressive functionality triggered by regulatory cells (MDSC and Treg) (3.A). This condition facilitates suppression of effector cells (NK and lymphocytes) in peripheral blood and in placenta triggered by MDSC (4.A), whereas Hofbauer cells maintain reactive species (NO) balanced (5.A) as well as the IFN-λ downregulation, IFN type I upregulation, and trophoblast autophagy (6.A), contributing to the cross-linking in the fetus-maternal interface. Adding to that, programmed cell death contributes to control the accelerated growth of neural cells in fetus brain (7.A), corroborating with a successful pregnancy. Zika virus has been related to abnormal pregnancy, leading to massive innate immune alteration, causing severe brain damage to fetus. Given that, when the virus is in the blood, there is a gross activation of innate cells, elevation of cytokines and chemokines (1.B, 2.B), and suppressive activity by regulatory cells is compromised (3.B), generating early activation of NK and T cells in blood (4.B) and macrophages in placenta (5.B). Virus invasion in placenta through Hofbauer and trophoblast cells results in high autophagy activity with interferon type I gene highly expressed combined with super downregulation of interferon type III (6.B). This imbalance also contributes to fetal brain damage, orchestra by high activation of apoptosis pathway, avoiding neural cells growing progress. Thus, Zika provides severe damage to fetus, in which drugs, vaccines and immunotherapies have been designed suggesting a modulation of three important keys of innate immunity to control virus replication and spread into fetus-maternal interface: interferon type III expression, MDSC frequency, and autophagy process (highlighted with red rectangles) to avoid severe fetus brain damage, allowing a healthy pregnancy. This figure was made based on the information from
The authors would like to thank Directory of Technological Development from Immunobiological Technology Institute, Biomanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil for founding support.
Authors to declare no conflicts of interest.
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The growing interest for using bio-polymers from renewable resources, such as wood/forest, corn, and cereals have spurred significant R&D developments toward the use of bio-polymers in green wood adhesives. 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The limited raw materials and the negative impact of synthetic adhesives on both human health and environment impose that further research is conducted with regard to renewable materials, in order to obtain environmentally safe bioadhesives that best fit their applicability domains.",book:{id:"6256",slug:"applied-adhesive-bonding-in-science-and-technology",title:"Applied Adhesive Bonding in Science and Technology",fullTitle:"Applied Adhesive Bonding in Science and Technology"},signatures:"Elena Dinte and Bianca Sylvester",authors:[{id:"202938",title:"BSc.",name:"Bianca",middleName:null,surname:"Sylvester",slug:"bianca-sylvester",fullName:"Bianca Sylvester"},{id:"218165",title:"Associate Prof.",name:"Elena",middleName:null,surname:"Dinte",slug:"elena-dinte",fullName:"Elena Dinte"}]}],mostDownloadedChaptersLast30Days:[{id:"39751",title:"Nonlinear Large Deflection Analysis of Stiffened Plates",slug:"nonlinear-large-deflection-analysis-of-stiffened-plates",totalDownloads:7325,totalCrossrefCites:0,totalDimensionsCites:2,abstract:null,book:{id:"2915",slug:"finite-element-analysis-applications-in-mechanical-engineering",title:"Finite Element Analysis",fullTitle:"Finite Element Analysis - Applications in Mechanical Engineering"},signatures:"Khosrow Ghavami and Mohammad Reza Khedmati",authors:[{id:"142986",title:"Prof.",name:"Khosrow",middleName:null,surname:"Ghavami",slug:"khosrow-ghavami",fullName:"Khosrow Ghavami"},{id:"143767",title:"Dr.",name:"Mohammad Reza",middleName:null,surname:"Khedmati",slug:"mohammad-reza-khedmati",fullName:"Mohammad Reza Khedmati"}]},{id:"39743",title:"Optimization and Improvement of Throwing Performance in Baseball Pitching Machine Using Finite Element Analysis",slug:"optimization-and-improvement-of-throwing-performance-in-baseball-pitching-machine-using-finite-eleme",totalDownloads:4855,totalCrossrefCites:1,totalDimensionsCites:1,abstract:null,book:{id:"2915",slug:"finite-element-analysis-applications-in-mechanical-engineering",title:"Finite Element Analysis",fullTitle:"Finite Element Analysis - Applications in Mechanical Engineering"},signatures:"Shinobu Sakai and Hitoshi Nakayama",authors:[{id:"141256",title:"Dr.",name:"Shinobu",middleName:null,surname:"Sakai",slug:"shinobu-sakai",fullName:"Shinobu Sakai"},{id:"143643",title:"Mr.",name:"Hitoshi",middleName:null,surname:"Nakayama",slug:"hitoshi-nakayama",fullName:"Hitoshi Nakayama"}]},{id:"57763",title:"Adhesives: Applications and Recent Advances",slug:"adhesives-applications-and-recent-advances",totalDownloads:2350,totalCrossrefCites:8,totalDimensionsCites:10,abstract:"Adhesives can be defined as social substances capable to join permanently to surfaces, by an adhesive process. 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MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. 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