\r\n\t
",isbn:"978-1-80356-951-2",printIsbn:"978-1-80356-950-5",pdfIsbn:"978-1-80356-952-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"bb6fc82b35ad2c63618a9bc15aeb61ce",bookSignature:"Dr. Kim Ho Yeap and Dr. Magdalene Goh Wan Ching",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11948.jpg",keywords:"MOSFET, CMOS, OFET, JFET, FinFET, Integrated Circuit (IC), Oxidation, Metallization, Semiconductor, Silicon (Si), Gallium Arsenide (GaAs), Silicon Carbide (SiC)",numberOfDownloads:5,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"18 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A researcher in the fields of microelectronics and electromagnetics. Member of IEEE, IET, IEM.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"24699",title:"Dr.",name:"Kim Ho",middleName:null,surname:"Yeap",slug:"kim-ho-yeap",fullName:"Kim Ho Yeap",profilePictureURL:"https://mts.intechopen.com/storage/users/24699/images/system/24699.jpg",biography:"Kim Ho Yeap is an Associate Professor at Universiti Tunku Abdul Rahman, Malaysia. He is an IEEE senior member, a Professional Engineer registered with the Board of Engineers, Malaysia,a Chartered Engineer registered with the UK Engineering Council, and an ASEAN Chartered Professional Engineer (ACPE). He received his BEng (Hons) Electrical and Electronics Engineering from Universiti Teknologi Petronas in 2004, his MSc in microelectronics from Universiti Kebangsaan Malaysia in 2005, and his PhD from Universiti Tunku Abdul Rahman in 2011. In 2008 and 2015, respectively, Dr. Yeap underwent research attachment at the University of Oxford (UK) and Nippon Institute of Technology (Japan). Dr. Yeap is the external examiner and external course assessor of Wawasan Open University. He is also the Editor in Chief of the i-manager’s Journal on Digital Signal Processing. He has also been a guest editor for the Journal of Applied Environmental and Biological Sciences and Journal of Fundamental and Applied Sciences. Dr. Yeap has been given the university teaching excellence award, and 22 research grants. He has published more than 100 research articles (including refereed journal papers, conference proceedings, books, and book chapters). Prior to joining the academic industry, Dr. Yeap worked in Intel corporation in the pre-silicon validation group. He was awarded 4 Kudos awards by Intel for his contributions in the design and verification of the microchip’s design for testability (DFT) features.",institutionString:"Universiti Tunku Abdul Rahman",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Universiti Tunku Abdul Rahman",institutionURL:null,country:{name:"Malaysia"}}}],coeditorOne:{id:"454196",title:"Dr.",name:"Magdalene",middleName:null,surname:"Goh Wan Ching",slug:"magdalene-goh-wan-ching",fullName:"Magdalene Goh Wan Ching",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Dr Magdalene Goh Wan Ching\r\nDesignation: Senior lecturer\r\nQualifications: Diploma in Electrical & Electronics Engineering (Inti College), BEng in Electrical\r\nEngineering & Electronics (University of Liverpool, UK), PhD in Solid State\r\nDevice Physics & RF Transistors Design (University of Liverpool, UK)\r\n\r\nProfessional Body\r\nMemberships:\r\n\r\nInaugural Senior Member, International Engineering & Technology Institute\r\n(IETI), Hong Kong\r\n\r\nBiodata: Dr. Magdalene Goh obtained her Diploma in Electrical & Electronics Engineering\r\nfrom Inti College before leaving for the UK to pursue her BEng in Electrical\r\nEngineering & Electronics and later on, her PhD. Prior to joining the academia,\r\nshe has worked for a few years in the industry in the areas of semiconductor\r\nprocess technology, silicon wafer characterizations, mask layout design,\r\nanalogue circuits design and design for testability (DFT). While in the academic,\r\nshe had served as a judge for Innovate Malaysia undergraduate final year\r\nprojects competition from 2012 - 2015. She had served as an external examiner\r\nfor a PhD candidate from VIT University, India in 2013, and an external examiner\r\nfor SEGi College Penang from 2014 – 2018. She has been actively involved with\r\nthe Penang Science Cluster in their radio telescope team since 2014, where she\r\nworks with a team of volunteers (from both academia and the industry in\r\nPenang) to create curricula in radio astronomy, for the purpose of introducing the\r\nconcepts of radio astronomy and radio telescopes to both school pupils and\r\ncollege students. She has been a member of the Astronomical Society of\r\nPenang since 2016.\r\n\r\nCourse Development\r\nExperience:\r\n\r\nSince joining WOU, Dr. Goh has developed eight courses, namely Control\r\nSystems, Microprocessors, Digital Communications, Microelectronics, VLSI\r\nDesign, Process Control & Instrumentation, Power Electronics & Drives and\r\nElectrical Power & Drives.\r\n\r\nResearch Interest: Dr. Goh’s research interests are in the areas of semiconductor physics and\r\nelectromagnetics. She also has strong interest in the field of astronomy and is\r\nworking with a group of volunteers to promote astronomy education in the\r\nsecondary schools in Penang. She had also worked with some interns on the\r\nradio telescope project at the Penang Science Cluster.\r\n\r\nResearch Projects and\r\nConsultancy Work:\r\nSelected Publications: Design of Radio Frequency Metal-Insulator-Metal (MIM) Capacitors. \r\n\r\nExperimental Investigation on Thermoelectric Generator for Battery - Charger\r\nBased Oven.\r\nAnalyzing the Physics of Radio Telescopes and Radio Astronomy (book\r\nchapters).\r\n\r\nConferences,\r\nSeminars and\r\nWorkshops:\r\n\r\nDr. Goh was appointed as one of the Technical Committee Member for the\r\nVirtual Conference on Electronics and Communication: Loading Intelligence on\r\nFuture Electronics (October 2020).\r\n\r\nHonorary\r\nAppointments and\r\nAwards:\r\n\r\nDr. Goh is a reviewer of the following journals:-\r\n1. Microwave and Optical Technology Letters.\r\n2. Journal of Electrical Engineering.\r\n3. Journal on Digital Signal Processing.\r\n\r\nOfficial\r\n\r\nDr. Magdalene Goh Wan Ching\r\nSenior Lecturer & Programme Coordinator of Bachelor of Technology in\r\n\r\nCorrespondence\r\nAddress:\r\n\r\nElectronics,\r\nSchool of Science & Technology\r\nWawasan Open University\r\n54, Jalan Sultan Ahmad Shah,\r\n10050 Penang\r\n\r\nEmail Address: magdalenegoh@wou.edu.my\r\nPersonal Homepage\r\n(optional):\r\n\r\nBTEL facebook page:\r\nhttps://www.facebook.com/groups/238200129533176/",institutionString:"Technology Wawasan Open University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:[{id:"82415",title:"Power Consumption in CMOS Circuits",slug:"power-consumption-in-cmos-circuits",totalDownloads:5,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@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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For experimental research, pressure has often been measured for its ability of revealing complex flow phenomena such as shock wave, boundary layer separation, etc.
\nConventional pressure measurement method is based on pressure taps and electronically scanned pressure transducers. Pipes connect these holes to pressure transducers, which transform the mechanical force of the pressure to a digital or analogy reading. Since the effective area for a single tap is rather limited, there could be several large arrays of hundreds or even thousands of pressure taps to be employed in industrial wind tunnel testing. Although these devices provide accurate pressure information, depending on the size and complexity of the model, the process of creating these models is time-consuming and expensive, while the preparation for wind tunnel testing is rather tedious and laborious. Thus it is the first drawback that using a pressure tap system needs much cost in time and labour and money. The other drawbacks include the fact that the number of taps should be limited because of the minimum space between pressure taps which lead to poor space resolution and the taps would introduce aerodynamic interference in wind tunnel testing which might affect the total pressure profiles along the pressure model surfaces as well as the difficulties of taps drilling and pipe arrangement on the surfaces with thin structures.
\nA new pressure measurement technique has been developed to augment the conventional surface pressure measuring method in aerodynamic testing, which actually is an optical-based technique using pressure sensitive paint (PSP). Compared to the conventional pressure measurement method, PSP technique provides a relatively simple and inexpensive way to acquire full-field pressure image on aerodynamic model surface with high spatial resolution and low aerodynamic interference resulting from PSP coating. Since it is with both functions of flow visualization and flow field measurement, PSP technique could reflect the details of flow structure on model surfaces such as traces of vortices, flow separation and reattachment and shock waves. The process of model-making and testing preparation is easy to manipulate with less time and less expense. PSP model needs less number taps for in-situ calibration and even the aerodynamic force model could be employed to acquire surface pressure distribution by PSP technique. If two-dimensional pressure data is mapped onto the three-dimensional model surface, aerodynamic force can be obtained by integration over the model surface.
\nPSP technique introduces an innovative concept of instrumentation and provides entire surface pressure map with high spatial resolution. In recent years, surface pressure distribution measurement technique using pressure sensitive paint (PSP) has been recently receiving popularity in the aerospace fields. The central Aero-Hydrodynamic Institute (TsAGI) [1,2] in Moscow, NASA [3–6] and McDonnell Douglas Aerospace (MDA) [7] are the PSP pioneers who published some PSP application results in wind tunnel, and the studied area includes the pressure distributions on the Delta-wing, the iced wing, the cooled film as well as famous combat fighter and civil transporter such as F-16, F-18 and several Boeing and Air Bus transporters. So far the convenient commercial PSP measurement system has been developed by ISSI (Innovative Scientific Solution Inc.). So Optical Pressure Measurement technique will act as an alternative to conventional methods for the pressure measurement.
\nThis section briefly reviews luminescence and quenching as it pertains to pressure sensitive paint. The image-based PSP technique is an optical method that enables measurements of surface pressure distributions over a model. More detailed discussions of these phenomena can be found in textbooks, for example, by Willard et al., Tianshu Liu.
\nPressure sensitive paint techniques are based on photoluminescence (which includes both fluorescence and phosphorescence) of some polymer probe molecules, as shown in Figure 1. When photons of particular wavelength impinge on the model surface with PSP coating, the probe molecule is promoted to an excited state by absorbing photons with appropriate energy. Then immediately excited probe molecule must return to the ground state by emitting photons of a longer wavelength to lose the excited energy. This process is called photoluminescence. Meanwhile, there exists other ways for excited molecules to lose energy, one of which is the process to transfer much excited energy to oxygen molecules penetrating into PSP coating by colliding and to decrease the emitting intensity, named as oxygen quenching. The working process of PSP involves those of photoluminescence and quenching, denominated as Stern-Volmer process, in which the intensity of PSP is inversed to the concentration of oxygen molecules.
\n\nSince the concentration of oxygen molecules in air is always consistent with 21% and that locally inside PSP coatings is proportional to the local pressure outside the coatings, locally low-pressure regions on the surface of a model will emit higher intensity with less quenching than locally high-pressure areas. Thus, pressure can be measured by oxygen quenching of luminescence.
\nBased on above mentioned photochemical characteristic of PSP, the working process can be modelled by a simplified form of the Stern-Volmer relation as:\n
Principle of optical PSP techniques.
Where
The preconditions for application of PSP technique are so strict and ideal that could never be achieved in practice. First, the uniform luminance on measured surfaces of model, consistent thickness of paint coatings and the distribution of temperature on measured surfaces must be kept the same. Furthermore, relative motion in position and structure distortion during operation should be prohibited, and ideal emission without spectral variability and filter leakage and the rest should be met.
\n\nThe most popular type of PSP technique is intensity-based method which acquires surface pressure distribution from the ratio image of intensity image at non-operation (wind-off) condition to that at operation (wind-on) by interpolated with pre-established Stern-Volmer equation. In most cases, some pressure taps values are essential and necessary to calibrate and validate PSP data, which process denoted as in-situ calibration. The intensity images are captured by scientific grade CCD or CMOS cameras which are either coloured or greyed type. Although the coloured camera only has one-fourth effective resolution of greyed one with the same nominal resolution, the former camera can provide at least two intensity image at same time. That is to say, the output of either camera is in grey level.
\nThe PSP measurement system should first be compatible to a particular test facility. The portable instruments or devices are necessary. Compatibility of a PSP measurement system to several test facilities is preferred. If compatibility is impossible, a flexible PSP measurement system should be established for cost-efficient purpose. The involved instruments or devices should be of high quality and of perfect performance. Thus the expense to establish PSP measurement system is not too low. An accurate PSP measurement system includes paint formulation, painting device, excited light source, scientific grade camera, calibration devices, image-processing device and software, and other auxiliaries such as filters etc. A perfect PSP measurement system has normally been promoted from an initially primary measurement system. Experience and expertise would play a critical role in the process of PSP measurement system establishment. Primary instruments or devices such as excited light source, calibration devices, image-processing software and filters should be customized, among which the selection of excited light source and filters depends on the spectral performances of paint formulations. The control devices will play an important role in multi-excited sources-and-cameras system. In addition, real time image processing is a perfect aim for PSP measurement system. A sketch of one PSP system configuration used in this investigation is shown in Figure 2.
\nComponents of optical PSP measurement system.
Detailed discussion of the PSP paint formulations are out of the chapter’s focus and only briefly described here.
\nA typical pressure-sensitive paint (PSP) is composed of two main components: oxygen-sensitive fluorescence molecules (which is called the luminescent probe molecules) and oxygen-permeable binder materials. From publications, PSP composed of pyrene or PtTFPP with oxygen-permeable silicon binder are popular in wind tunnel testing, the former of which exists an absorbing peak near 320 to 340 nm among an exciting range from 320 to 390 nm and an emission peak near 440 to 520 nm, the latter of which is excited near 400 nm and then emits a main peak near 650 nm. The pyrene-based paint is developed by ICAS (Institute of Chemistry, Chinese Academy of Science), is insensitive to thermal changes when ambient temperature is below 40°C. Therefore, the spectral characteristic of the used PSP paint should be acquired by the calibration for measurement accuracy.
\nCleaning surface with acetone.
Spraying the paint on the surface.
Fine paint application is the basis of PSP measurement which needs specific expertise and experience. There are several steps for operation. First is to remove oil dots, dust and other dirt spots on the model surface needed paint applying with alcohol or acetone (as shown by Figure 3). Any surface imperfections that are unwanted should be corrected prior to a final cleaning. Once the model is completely cleaned, model parts that are not to be painted are covered with tape and/or paper. This step assures the surface to be absolutely clean. Second is to spray base coat or primer coating with an air brush on the cleaned model surface and then to cure the primer coating by lifting ambient temperature for several hours or at ambient temperature for more than 12 h. To finish, the cured primer coating with fine sand papers 800–1500 grit. Finishing will promote the uniform coating thickness and enhance the reflection of excited and emission light. Then remove finished dust attached on the coating by spraying mixture of air and acetone. Third is to spray upper coating containing probes molecules as seen in Figure 4. The primer coating is over-sprayed with a saturated solution of probe molecule in toluene or acetone. Several over-spray coats are continued until an even colour (deep pink from ISSI or sky blue from ICAS, seen in Figure 5, which is dependent on the PSP formulation) is obtained. And then cure it as the same process as the second step. Fourth is to arrange markers on the cured coating for image alignment which will be described in the following section.
\nSurface coated with PSP. (a) Paint from ISSI; (b) paint from ICAS.
The paints are applied using a commercial automotive type spray air brush (Figure 6) and clean, dry, regulated service air (Figure 7). A high volume low pressure (HVLP) touch up sprayer has produced excellent results. Here, the nitrogen is suggested for sprayer instead of the air to avoid the interaction from the oxygen. HVLP sprayers have become standard with their compliance with environmental standards. Jet pressure and area of the sprayer is regulated according the performance of the paint layer. Paint should be sprayed in an area with adequate ventilation. Personal protective equipment must be used depending on the materials being sprayed and the location where the paint is applied.
\nSpraying air brush (W-71G).
Oil and water filtering regulator for spraying air brush.
Pressure sensitive paint working process is denoted as Stern-Volmer process as mentioned previously. The purpose of the excitation light source is to excite the photo luminescent probe molecules. The source must provide an adequate number of excitation photons within appropriate wavelengths. The excited source should avoid emitting photons with wavelength overlap incident photons. Otherwise, Signal Noise Ratio (SNR) of scientific grade camera will decrease to very low level. A range of illumination sources have been considered including lasers, filtered arc lamps, and LED, etc. Here, UV lamp and LED are tested and used.
\nBased on the feature of the paint layer from ICAS, a Porta-Ray 400 portable ultraviolet (UV) lamp made by Uvitron International Company in the U.S. is chosen in the current work, which is a 400W/200W, 1000 h lifetime metal halide lamp. It can emit visible light in a broad spectrum and the maximal output intensity is up to 500 MW/cm2 within UVA range, whose practical output instability is less than 5%, especially less than 1% after running 30 min.
\nAdditionally, a filter box (Figure 8) was designed and manufactured to filter visible light and select UVA light to excite the probe molecules, which consists a metal box, a scattered quartz glass and two pieces of UVA transparent glasses filter. With a pair of latches, the filter box is connected with the UV lamp to form the integrated excitation light source.
\nUV lamp and filter box.
The arrays consists of 37 individual LED (light emitting diode) elements (3W) arranged on a 9.0 cm diameter aluminium substrate and is equipped with water cooled equipment (Figure 9) to insure pure illuminating light. The LED array produces light centred at 365 nm (∼20 nm full width at half maximum) which is the optimal excitation wavelength. The uniformity of the spot area is beyond 92% with irradiation height of 120 mm. The LED arrays are operated using a 300W switching power supply and can be remotely operated using standard TTL pulse or with continues irradiation mode.
\nPhoto of LED arrays and controller.
Considering the higher readout noise and nonlinear response at low intensity situation, industrial CCD or CMOS camera generally is not fit for accurate PSP measurement. This leads to generation of relatively low SNR (Signal-To-Noise Ratio) Image to decrease its quality. In general, scientific grade CCD or CMOS camera is preferred because its readout noise has been well controlled, and linear response to low intensity has been carefully corrected to satisfy the request of PSP measurement.
\nIn initial study, a TSI charge-coupled device camera (CCD, 1600×1200 pixels, 10 bit) from a Stereo PIV system is chosen as the luminescence photo detector. The image sample is controlled by PIV operating software, INSIGHT 6.0, automatically.
\nIn current study, PSP luminescent emission data is acquired by a specialized air cooled scientific charge-coupled device (CCD) ORCA-R2 camera. A combination of a 24–85mm Nikon zoom lens and 480 nm band pass filter is used in front of the CCD to block excitation. This low noise device allows for the rapid collection of image pairs with a minimal time delay between images. The camera employs a CCD chip with an active area of 1344×1024 pixels with 0.008 ms exposure time and its quantum efficiency is greater than 70% at the wavelength range of 450 nm to 600 nm, which covers the (480 ± 20) nm emission from PSP, and more than 50% near 650 nm. The camera employs 16-bit digital resolution as well as on-board memory that will allow it to rapidly store images; also it provides the high-dynamic range model at 8×8 binning readout if necessary.
\nIn order to maintain the accuracy of PSP measurement, a calibration device was designed and manufactured, which integrates pressure and temperature adjustors with adequate precision as well as a mediate pressure air pump and an integral cooler and heater. Calibration vessel was customized, which is a steel cylinder with 100 mm diameter ×100 mm high × 8 mm thick and attached with a shrouding ring 20 mm wide atop the plate (Figure 10). It is covered with a piece of quartz glass or Plexiglas and connected with a pair of holes as inlet and outlet. With the help of a pressure or vacuum pump, the gas pressure in the pressure vessel can be adjusted 0–200kPa through a pressure manometer.
\nPhoto of pressure vessel.
Image processing is a critical step in the whole optical PSP measurement. The current image processing is divided into three parts as shown in Figure 11: basic data processing, image registration and 3D reconstruction [8].
\nSchematic representation of major steps in PSP data processing.
Transformation from ratio image to pressure map is manipulated with Stern-Volmer Eq. (1) in which Stern-Volmer constants have been determined through a priori calibration. The luminescence
Generally, the condition of wind-off and wind-on is denoted non-operation and operation of the wind tunnel. It is clear that wind-off means reference condition in Stern-Volmer Eq. (1).
\nIt should be mentioned that the number of images captured at wind-off and wind-on depends on the performances of PSP measurement system, environment and operation condition of the wind tunnel. Besides, a number of dark images and background images should be captured before and after operation respectively. The random noise such as photon shot noise etc. should be restrained by averaging the respective images. The algorithms to suppress the noise generated in image calculations should be chosen carefully because most of them would decrease the effective resolution of selected images.
\nIn practice, the model surface could move or distort during operation of wind tunnel due to aerodynamic loads and vibrations. Thus, there exist space displacement, structure bending and structure torsion in operation. The situations introduce the difficulties in image ratio calculation due to displacement and structure variation. Hence, image registration must be employed to solve this problem. The wind-on image may not align with the wind-off image due to model deformation produced by aerodynamic loads. Figure 12(a) displays an unregistered intensity ratio image of a compressor cascade suction surface, which shows a shadow near each pressure port, as well as two strip-like shadows along leading and trailing edges. The occurrence of shadows might be ascribed to not aligning of wind-on and wind-off images. A ratio between those non-aligned images can lead to a considerable error in calculation of pressure using a calibration relation. Significant errors are introduced if these effects are not included, particularly in regions of rapid pressure changes such as near shock waves, boundary layer transition and flow separation.
\nTo match the deformed pressure image coordinates (
Image of unregistering (a) and registered (b).
Where both basic functions
In fact, it is very common that the axis of camera lens is not perpendicular to the surface of interest. Thus, 2D pressure map would not provide detailed useful information when normal direction of captured images is not parallel to that of the interest surface. In special case such as testing in cascade wind tunnel, the image is rather distorted and unable to provide more detail on interest surface. To reproduce the pressure map on the 3D test model, 3D reconstructing method is developed based on the projective theory of photogrammetry [9–11].
\nThe perspective relationship between the coordinate (
Perspective between 2D image and 3D model.
With the help of the over six marks, the transforming coefficient
Flow chart of 3D reconstruction.
When a set of PSP measurement system has been established, it should be corrected and validated via several PSP calibrations using mature PSP formulation. This is the basis for practical PSP applications.
\nHaving established the PSP measurement system, the validation of its performances and the investigation of selecting relevant system parameters have been conducted in Laboratory of Aerofoil & Cascade Aerodynamics, Northwestern Polytechnical University (NPU). More detailed work has been published in the reference [12,13]. During the calibration process, it is kept dark in the ambient to avoid lighting contamination.
\nA sample coated with the paint layer is placed in the pressure calibration vessel bottom, which is about 50 mm×50 mm. According to a cascade transonic wind tunnel, the pressure calibration range is determined from 27.4 kPa to 217.4 kPa with interval 10 kPa. To optimize the measurement system, the calibration experiment is performed with five apertures of CCD (2.8, 4, 5.6, 8 and 11) and two powers of UV lamp (200
Figure 15 shows the original PSP images under typical pressures using two power settings of UV lamp on the condition that the camera aperture is 2.8. There is an inverse relationship between the emitted light intensity and the local air pressure according to the oxygen quenching characteristics of the PSP. Thus, with the pressure increasing, the image is getting darker as shown in Figure 15, which is in agreement with the principle of PSP technique. Furthermore, it is very clearly observed by naked eyes that the image Figure 15(b) using 400
To show the difference between Figure 15(a) and (b) more clearly, the luminous intensity of the image is quantified using the grey value of the model surface centred point in Figure 16. The luminous intensity using 400
Images using two powers of UV lamp. (a) 200W power; (b) 400W power.
Figure 17 shows the PSP calibration curves using both 200
Luminous intensity frame using two powers of UV lamp. (a) 200W power; (b) 400W power.
Calibration curve using two powers of UV lamp with typical apertures at 2.8 (a), 5.6 (b) and 11 (c).
It was also found from Figure 17 that the setting of CCD aperture has an influence on the measured result. In the present study, the optimization of CCD aperture (2.8, 4.0, 5.6, 8 and 11) is performed with 400
Images with typical CCD apertures at 5.6 (a) and 11 (b).
Luminous intensity frame with typical CCD aperture at 4 (a) and 8 (b).
To show the influence of the CCD apertures more clearly, the luminous intensity of the image is quantified using the grey value of the model surface centred point in Figure 19. Sampled data using different CCD apertures show higher linearity using the 400
All calibration curves with five CCD apertures are shown in Figure 20. The calibration curves are very close when the CCD aperture is set as 4 and 2.8. The calibration curve becomes steeper with the CCD aperture increasing and is nearly linear when CCD aperture is 11. Clearly, due to the improved SNR (Signal Noise Ratio) of CCD, the pressure calibration curve is mostly sensitive to the pressure change and keep better monotonic when the CCD aperture is 11, especially when the pressure is higher.
\nCalibration curve in different apertures.
In the references [13–15], the two sets of PSP experiment are performed in a transonic cascade wind tunnel: one is based on the self-established PSP system, the other based on the commercial PSP system by ISSI. And the global pressure distributions on two sets of compressor blade are measured on several inflow conditions. Finally, PSP results are compared with that with the traditional measurement technique.
\nSchedule of cascade.
PSP experiments are carried out in the Science and Technology Key Lab’s transonic cascade wind tunnel in Northwestern Polytechnical University (NPU). The experimental cascade is composed of several blades and two end-walls (see Figure 21). In the present work, two sets of the PSP measurement system are used: one is the own established PSP system by ourselves, and the other is the commercial PSP system produced by ISSI. Correspondingly, two sets of cascade are provided as the PSP measured model: blade1 is coated with PSP from ICAS (Institute of Chemistry, Chinese Academy of Science) in Figure 22, and blade2 iss coated with PSP from ISSI in Figure 23.
\n\nBlade 1 coated with ICAS PSP.
Blade 2 coated with ISSI PSP.
Based on the established measurement system, the pressure distribution on blade1, whose chord is 56.7 mm, bend angle is 52.6°, height is 100 mm, is measured under two conditions: Ma=0.4 and Ma=0.5. with the same incidence angle (i=−10°).
\nStatic pressure distribution on suction surface at Mach 0.4 (a) and Mach 0.5 (b).
Figure 24 shows the pressure distribution on suction surface at Mach 0.4 and Mach 0.5 respectively. From two pressure map, there is a high pressure area near the leading edge. Under the action of the large negative attack angle and the larger pitch between two neighbourhood blades, the inflow injects onto the blade leading edge and decelerates quickly, consequently, the pressure increases. Then, airflow began accelerating and the pressure decreases because of the large curvature on blade surface. At 40% chord, airflow accelerated to max and a pressure valley is shown in the pressure map. Due to the divergence of the cascade passage, pressure grows up again. In addition, due to the boundary layer interfering mutually between end-wall and blade surface, pressure at the corner between the end-wall and blade surface is smaller than the other area.
\n\nAlthough there are two results at different Mach number in Figure 24, there is the same pressure distribution trend on suction surface, and the surface pressure is increasing with the rising inlet Mach number.
\n\n\nTo test the measurement precision of PSP technique, the averaged-pressure around pressure holes is compared with the pressure measured by conventional pressure tap, and the results are shown in Figure 25. In the plot, X-coordinate shows the relative chord, Y-coordinate shows dimensionless pressure.
\n\n\nFrom Figure 25, it is seen that the pressures measured by PSP technique and pressure tap follow the same trend in two different conditions. The position of the lowest pressure on blade suction surface coincided nearly. The pressure error at the same position is less than 4.5%, which meets the engineering application basically.
\nPressure on the 50% span at Mach 0.4 (a) and Mach 0.5 (b) using PSP and pressure scanner.
Based on the ISSI PSP system, the pressure distribution on blade 2, whose chord is 69.946 mm, pitch is 60.7 mm, height is 100 mm, is measured using ISSI PSP under three conditions: Ma=0.4, 0.5 and 0.6 with the same incidence angle (i=0°).
\nFigure 26 shows the pressure distribution on suction surface at Mach 0.4, 0.5 and 0.6 respectively. It shows that the distribution of pressure in different conditions has almost the same trend. While with the increase of the inlet Mach, the pressure at the same position decreases. Similar to the blade 1 results, the pressure at the corner of blade 2 between the end-wall and blade surface is smaller than the other area due to the boundary layer interfering. Besides, the pressure increases along the blade chord due to the divergence of the cascade passage.
\nStatic pressure distribution on suction surface at Mach 0.4 (a), 0.5 (b) and 0.6 (c).
To test the measurement precision of PSP technique, the averaged-pressure around pressure holes is compared with the pressure measured by conventional pressure tap, and the results are shown in Figure 27. In the plot, X-coordinate shows the relative chord, and Y-coordinate shows dimensionless pressure.
\n\nFrom Figure 27, it is seen that PSP measurement results have the same pressure distribution trend to the pressure scanner results on the two conditions. The position of the lowest pressure on blade suction surface coincided nearly. The pressure error at the same position is less than 4.5%, which meets the engineering application basically.
\nPressure on the 50% span at Mach 0.4 (a), 0.5 (b) and 0.6 (c) using PSP and pressure scanner.
Pressure Sensitive Paint measurement technique is attracting extensive attention for its unique advantage at surface pressure measurement, such as the absence of intruding measured surfaces, application of image processing to acquire global pressure distribution, and the acquisition of PSP results that traditional methods could never obtain. In this chapter, both the theory and application of PSP technique are introduced, including the measurement principle, measurement system, component characteristics and its application in internal flow fields based on author’s researches. The results are proposed for engineering application.
\nThis work was supported by the National Nature Science Foundation of China (NSFC) under the Grand No.51476132. Besides, Dr. Zhou Qiang was acknowledged for his valuable suggestion.
\nSARS-CoV-2 is a relatively large virus with single-stranded RNA genome, belongs to beta coronaviruses that affects the lower respiratory system to cause viral pneumonia. The gastrointestinal system, kidney, heart, liver, and central nervous system may also be attacked leading to multiple organ failure. It is surrounded by an envelope composed of a lipid bilayer and envelope proteins [1].
The COVID-19 viral infection is mediated by three main stages: the first one involves host cell entry through endocytosis and transportation proteins; the second stage initiates viral RNA translation to polyprotein, which is subjected to cleavage by the main viral proteinases Mpro and Papain-like proteases PLpro to produce the effector proteins; in the final stage, the negative-strand viral RNA is translocated to the Golgi apparatus to produce new virions, and the newly produced virus are released by exocytosis [1].
The viral entry was found to be mediated by endocytic pathways, which is initiated by the binding of spike protein (S protein), a protein found on the envelope of the virus, to a receptor protein located on the host cell surface membrane, known as angiotensin-converting enzyme 2 (ACE2). The S protein is cleaved into S1 and S2 by a human cell-derived protease that is assumed to be Furin. S1 then binds to its receptor, ACE2. The other fragment, S2, is cleaved by TMPRSS2, a serine protease. Thus, ACE2 and TMPRSS2 are essential in airway cells for SARS-CoV-2 infection [2].
Also the viral entry was found to be facilitated through endocytosis [3], especially clathrin-mediated endocytosis (CME) helps in translocation of ACE-2/virus complex to endosome where the virus is uncoated by the action of acidic proteases such as cathepsins, which are cysteine proteases in host cells involved in facilitating viral entry of several viruses such as SARS-COV and MERS-COV [4]. It’s worthy to note that cathepsins are also involved in S protein cleavage [5, 6].
After uncoating, the viral RNA expression and replication require subcellular localization of viral and cellular proteins from cytoplasm to the nucleus. The viral infection induces the translocation and expression of group of suprafamily protein in the host cells called karyopherin, Importins (IMP) α/β heterodimer. These proteins are reported to be utilized by the virus not only for translocation purposes, but also for disruption of self-antiviral defenses in response to interferon via intervening with the nuclear import of signal transducer and activator of transcription proteins (STAT). Chromosome Region Maintenance-1 (CRM1) is one of those proteins that contribute significantly in nuclear export of viral protein and RNA in wide range of viruses [7].
The SARS-Cov-2 genome has a large replicase gene, which contains nonstructural proteins (NSPs), structural proteins, and accessory genes. The replicase gene encodes two open reading frames (ORFs) after frameshifting, translated into two large polyproteins pp1a and pp1ab, then processed by two viral proteases: papain-like protease (PLpro, encoded within Nsp3) and Mpro aslo called 3C-like protease (3CLpro, encoded by Nsp5) to produce 16 viral Nsps that their function has been linked to RNA replication. PLpro is believed to play important role to protect the virus from immune response by inactivating ubiquitin-dependent cellular responses to viral infection and blocking of cytokine production [8, 9].
After cell invasion, a full-length negative-strand RNA template is synthesized by nonstructural protein 12 (Nsp12) RNA-dependent RNA polymerase (RdRp) to produce more viral genomic RNA [10].
Another important nonstructural protein is RNA helicase, which has main role in the replication of viruses by catalyze unwinding of double-stranded RNA. It is structurally conserved among different types of viruses, thereby making it an excellent target for development of broad-spectrum antiviral agents [11, 12].
In this stage, the viral RNA is translocated to endoplasmic reticulum (ER) where it is translated to transmembrane structural proteins (S, HE, M, and E) and some membrane-associated accessory proteins, except for the N protein, which is translated by free ribosomes in the cytoplasm [13]. These structural proteins play the main role in virion morphogenesis and the structural components recruitment to the proper assembly site. Then they are released from the cell by exocytosis by the help of several host factors [14].
However, in the COVID-19 pandemic, an integrated approach encompassing prophylaxis, diagnosis, and treatment must be adopted worldwide.
Among the top priorities for regulating and monitoring COVID-19 are:
An appropriate prophylactic procedure (vaccination).
Accurate diagnostic battery.
An unambiguous therapeutic regimen.
WHO stated that “vaccine must supply a quite convenient beneficial environment for dealing with jeopardy; with high performance, only passing with mild effects and with no danger effects.” The vaccine should be appropriate for lactating, gravid women and for all ages and has many production sources dwell in high-, middle-, and low-income countries [15]. There is a race among several pharmaceutical companies to provide a treatment for COVID-19. Unfortunately, this completion had led to a big controversy, which was refuted by WHO issued on 20 November 2020 “there is a conditional recommendation against the use of remdesivir since there isn’t enough evidence to support its use.” Moreover, WHO has issued a conditional recommendation against the use of remdesivir in hospitalized patients, regardless of disease severity, as there is currently no evidence that remdesivir improves survival and other outcomes in these patients (https://www.who.int/news-room/feature-stories/detail/who-recommends-against-the-use-of-remdesivir-in-covid-19-patients).
However, by the end of 2020 (exactly December 2020), Pfizer/BioNTech was able to get an Emergency Use Listing approval (EUL) for vaccine against COVID-19. Currently and as reported by on January 20th, 2022, nine vaccines were granted EUL status [16, 17].
The Pfizer/BioNTech Comirnaty vaccine, 31 December 2020.
The SII/COVISHIELD and AstraZeneca/AZD1222 vaccines, 16 February 2021.
The Janssen/Ad26.COV 2.S vaccine developed by Johnson & Johnson, 12 March 2021.
The Moderna COVID-19 vaccine (mRNA 1273), 30 April 2021.
The Sinopharm COVID-19 vaccine, 7 May 2021.
The Sinovac-CoronaVac vaccine, 1 June 2021.
The Bharat Biotech BBV152 COVAXIN vaccine, 3 November 2021.
The Covovax (NVX-CoV2373) vaccine, 17 December 2021.
The Nuvaxovid (NVX-CoV2373) vaccine, 20 December 2021
The clinical laboratory is an important and essential tool for the diagnosis, follow-up, and evolution, as well as in the prognosis of any pathology that is active or not. In the COVID-19 pandemic, several biomarkers’ involvement as indicators of the disease’s current state has been reported, while others have proved to be useful prognostic markers. Some of these characteristics are as follows [18].
General laboratory findings in SARS-CoV-2 infection sometimes indicate leukocytosis or leukopenia, with marked lymphopenia in the disease’s first stages. Besides, the neutrophilia presence has been related to an unfavorable prognosis [19].
Thrombocytopenia, lymphopenia, thrombocytopenia, D-dimer, elevated C-reactive protein (CRP) (happened repeatedly in critical cases), and leukopenia are not distinctive laboratory factors [20].
COVID-19 patients who have diabetes mellitus of type 2 (T2DM) expressed minimized levels of lymphocytes, body mass index (BMI), albumin, and uric acid (UA), and increased CRP levels. The reduced levels of albumin, UA, and BMI may be related to nutritional consumption and oxidative stress response. The increased CRP levels and decreased lymphocyte counts may be related to the infection [21].
Medical imaging, such as Computed Tomography (CT) and X-ray, plays a significant function in the combat against the pandemic. So, the current AI methods can be used to help medical specialists and strengthen imaging tools. Also, AI could also increase work performance by effective detection of CT and X-ray diseases. The Computer-Aided Diagnosis (CAD) models enable physicians to take correct clinical choices on disease diagnosis, monitoring, and prognosis [22]. Many radiological characteristics are used to categorize the disease and help in discovering the treatment, such as the following:
The most direct method to identify the degree of disease is imaging, as it is effective and accurate. Consolidation and diffuse lesions are features of severe pneumonia. Doubled ground-glass opacity, unification, and interlobular septal thick ply in the right and left lungs are the popular chest CT discoveries for COVID-19, which are particularly spread under the pleura. The serious part of the pandemic diagnosis and examination is computed tomography [23].
A sensitive examination method is called spiral CT. It can be used for diagnosis in the early stages and estimation of development. This method has diagnostic allergy and precision preferable to the disclosure of nucleic acid [24]. During the first week of the illness, appearance and blended predominance with opacity in the lower lung are quite dubious of COVID-19. However, few illness cases may have a normal chest outcome despite positive testing for COVID-19 [25].
The proportion of infected cases with mild COVID-19 symptoms was relatively high-rise. Misdiagnosis in some cases can result from checking for COVID-19 with only chest CT, which would result in a possibility of contagion risk. It was not appropriate as a separate screening device. Visual, quantitative interpretation depended on CT images with great diagnostic capability and good matchmaking. It can help in clinical classification; it is predictable to strictly evaluate the severe COVID-19 cases and combining with the clinical information to guide the clinical treatment [26].
Therapeutic interferences can be categorized into four main classes: general treatment, antiviral treatments, particular medications, and other medications.
The effectiveness and safety of COVID-19 have been tested using several drugs, such as chloroquine, remdesivir, favipiravir, and hydroxychloroquine. Some of them had presented antiviral impacts against COVID-19 but no conclusive evidences [27].
Although the serious disease has been related to hyperinflammation induced by COVID-19, the immune responses of acute COVID-19 stay ambiguous. Some researchers comprehensively analyzed circumferential immune troubles in blood for 42 recovered and infected by COVID-19. The activation of various immune strains is recognized, including oligoclonal plasmablast expansion, trafficking receptor modulation on granulocytes, innate lymphocytes, and T cell activation, which separated acute COVID-19 patients or moderate-severe patients from healthy donors or COVID-19-recovered. One of the predictive biomarkers is the ratio between neutrophil and lymphocyte of organ failure and disease gravity. Results appeared wide innate and adaptive leukocyte annoyances that characterize dysregulated have an infection in extreme COVID-19 disease, and medication examination is required. There were no efficacious antiviral medications, even common drugs with strong effect as abidol, ritonavir/lopinavir showed no exceptional impact on clinical progression, virus clearance, or deaths [28].
The meta-analysis of corticosteroid treatment and available observational studies suggested maximized death rates and subaltern contagion rates in influenza, maximized viremia, weakened antibody response, and weakened infection riddance MERS-CoV and SARS-CoV, and corticosteroid treatment complications in recovered patients [29]. Therefore, in the medication of COVID-19, corticosteroids should not be supported or even applied for acute patients.
The plasma of convalescent for severe influenza infection and SARS-CoV medication was proposed to minimize the mortality rate and days number in hospital, particularly after symptom appearance and administered plasma early [30].
As for inoculation, if any cross-reactive epitopes were recognized among COVID-19 and SARS-CoV, the preceding vaccine of SARS-CoV might be reused to expedite the COVID-19 vaccine progression. It is recommended for prophylaxis, streptococcus pneumonia, and influenza vaccination, especially in the elderly [31].
Drug repurposing is also a quick tool that creates a shortcut to find a safe and effective therapy for this exciting pandemic. It depends on the fact that their safety profile, side effects, posology, and drug interactions are well known [27]. Currently, several FDA-approved drugs are tested for their potential to treat COVID-19 infection such as lopinavir, chloroquine, azithromycin, hydroxychloroquine, favipiravir, umifenovir, ribavirin, remdesivir, and darunavir have been tested in many COVID-19 clinical experiments for hopeful use under emergency protocol. Unfortunately, none of these tested drugs showed a conclusive results and satisfactory outcomes among treated patients. Therefore, several studies used in silico tools for prediction of the ability of drugs to interact with molecular targets important for viral replications.
In that aspect, the liver research laboratory (FAB-Lab, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt) has applied several approaches for not only improving the pharmacological effect of easily accessible natural products, but also identifying new applications for them. Drug repositioning or repurposing may reveal a new approach to rediscover new uses for clinically approved existing old drugs [32].This book revealed the theory, applications, and/or hazardous outcomes on drug discovery in different disciplines in medicine; e.g. dermatology [33, 34], cancer [35, 36, 37], and neurological disorders [38].
A hopeful mechanism to cure COVID-19 patients is the reusing of trusted antiviral treatments in opposition to COVID-19. Viral loads are reduced by employing the antiviral treatments that have risen lung allocations, which is helpful to COVID-19 cases. There are a number of antiviral medications such as [39]:hr
Some results depended on molecular docking and network direct pharmacology action on COVID-19, for examples:
Kaempferol, aloe-emodin, quercetin, luteolin, forsythoside E, rutin, and hyperoside in Lianhua Qinwen might be the buoyant components in hindering COVID-19 by computer-assisted treatment design (CADD) of virtual checking and network pharmacology analysis through JAK-STAT signaling pathway [40, 41, 42]
Patchouli alcohol, saikosaponin ergosterol, 23-acetate alisol B, shionone, B (Bupleuri Radix) could act straight on the COVID-19 3CL pro to restrain infection multiplication. On differentiate, shionone (Asteris Radix et Rhizoma), tussilagone, patchouli alcohol, asarinin, ephedrine hydrochloride, and ergosterol might work on steward cells ACE2 to restrain the attack [43, 44, 45, 46]
Licorice glycoside E, (2R)-7-hydroxy-2-(4-hydroxyphenyl) chroman-4-ketone, robinin, naringenin, quercetin, kaempferol, irisolidone, and isorhamnetin from Huoxiang Zhengqi as 3CL pro restraints, which may block COVID-19 repetition by focusing on E2F1 and PIK3CG by PI3K-Akt signaling path [44]. Rosmarinic acid could block virus repetition through the PI3K-Akt signal path [47].
Quercetin, Kaempferol, luteolin, baicalein, glyasperin C, licochalcone B, and oroxylin A were suggested to tie with organizing different signals paths and ACE2, as BCL2, PTGS2, Kaposi sarcoma-related herpesvirus contagion, CASP3, hepatitis C, Epstein-Barr virus infection, measles, and human cytomegalovirus contagion.
Baicalein, kaempferol, luteolin, rhubarb wogonin, and quercetin had a great partiality with COVID-19 3CL hydrolase [48].
As previously explained, nonstructural proteins of COVID-19 and several factors and receptors in host cells are essential for viral entry and replication, which means that both should be considered in the process of the development of effective antiviral agents as depicted in Figure 1. In this section, we will address known natural products inhibitors to the key targets controlling viral entry and replication.
Different approaches for targeting viral entry and replication of the COVID-19. (1) Inhibition of S protein binding to ACE2, (2) disruption of endocytic pathways, (3) inhibition of nuclear translocation of viral RNA and protein by host cell mediators, (4) inhibition of the proteolysis of viral polyprotein to the nonstructural proteins (Nsp), (5) inhibition of transcription and replication of viral RNA.
Targeting host lipids is an intriguing antiviral strategy. Coronaviruses are a class of viruses with a lipid envelope that requires a plasma membrane fusion process mediated by endocytosis, a mechanism that involves certain cholesterol-rich microdomains and its ACE2 receptor [49] and mediates the early stages of internalization of coronaviruses [50].
Macromolecules such as methyl-β-cyclodextrin have been used to inhibit attachment of coronaviruses to host cells. These nontoxic macromolecules mimic attack sites for the enveloped virus, competing with host cell attack sites. It could also decrease ACE2 expression in the cell membrane, thereby reducing the infectivity of coronaviruses, such as SARS-CoV-2 [51].
Natural compounds including phytosterols and triterpenes (Figure 2) can exert the same action. For example, betulinic acid also has the same lipophilic properties as cholesterol, so it may therefore compete with cholesterol, replacing it in plasma membranes, or it may bind to the virus instead of raft cholesterol, acting as a soluble competitor [52].
Chemical structures of the most common phytosterols. They are considered as potential inhibitors of SARS-CoV-2 lipid-dependent attachment to host cells, a possible approach for decreasing its infectivity.
TMPRSS2, a human cell surface serine protease, results in membrane fusion. ACE2 and TMPRSS2 are essential in airway cells for SARS-CoV-2 infection [53]. ACE2 inhibition should not be tracked as a treatment strategy as ACE inhibitors upregulate the expression of ACE receptors providing more binding sites for SARS-CoV-2. On the other hand, blocking TMPRSS2 is accessible and will prevent the fusion of the envelope of the virus with host cell surface membranes. Nafamostat, an existing safe drug used for pancreatitis, may inhibit SARS-CoV-2 entry by inhibiting TMPRSS2 activity.
In this context, several reported serine protease inhibitors from nature could be repurposed to target TMPRSS2.
Potent serine protease inhibitors have been reported from filamentous marine cyanobacteria. Most of these molecules are 3-amino-6 hydroxy-piperidone (AHP-containing cyclic depsipeptides). The AHP moiety is crucial for serine protease inhibitory activity, and any structural or conformational variations to this unit will affect activity (Figure 3) [54].
Serine protease inhibitors isolated from marine cyanobacteria. Potential blockers for the requisite viral entry process (inhibition of the S protein-initiated membrane fusion by inhibiting TMPRSS2 activity).
It’s now well established that endocytosis is the nick bottle for COVID-19 entry to the host cells, thus inhibiting this pathway could reduce the infectivity of the virus dramatically. This could be achieved by increasing of the endosomal and lysosomal pH using lysosomotropism agents, which disrupt the proteolytic action of host cell proteases, which work optimally in acidic pH and prevent the cleavage of the S Protein of the virus [55]. While chloroquine (CQ) and its derivative are developed originally for treatment of malaria, but since they demonstrated potent activity by direct acting on the virus and by preventing its endocytosis, they were repurposed for treatment of several viral infection and currently used widely used in therapeutic protocol for treatment of COVID-19 [56]. Bafilomycin A1, a vacuolar-type H+−ATPase inhibitor, lies in the same category and could explain the use of azithromycin, a structurally related macrolide antibiotic for treatment of COVID-19 patients [57].
Inhibition of cysteine proteases such as cathepsins could be an important approach due to their role in viral entry, and luckily the incorporation of these protein in the pathogenesis of several diseases such as cancer, metabolic conditions, and Alzheimer’s has led to the discovery and development of several inhibitors that could be repurposed for treatment of COVID-19 infection. E-64, a compound isolated from the fungus
As addressed earlier, CME is one of the main mechanisms for viral entry; hence, its inhibition could be a reliable method for control of the infection. Ouabain and bufalin cardiotonic steroids, which are used for treatment of cardiovascular diseases, have demonstrated antiviral activity against MERS-CoV infection at nanomolar concentrations by affecting the CME pathway [59]. This is consistent with recent report by Jeon et al., where ouabain, lanatoside C, and digitoxin were able to reduce viral viability of COVID-19 in micromolar concentrations [60].
Bolinaquinone, a sesquiterpenoid derivative with quinone ring, isolated from marine
Like other viruses, COVID-19 uses the replication machinery of the host cell for transcription and replication of Viral RNA; this means that viral materials such as nonstructural proteins and negative-strand RNA should be relocated to the nucleus and endoplasmic reticulum.
Interestingly, ivermectin, an antiparasitic FDA-approved drug, has been reported to inhibit nuclear transport in host cells such as (IMP) α/β1 heterodimer preventing the translocation of viral DNA integrase in HIV-1 and other viruses. Recently, ivermectin has shown potent antiviral activity against COVID-19 [63]. In fact, such effect was linked to the broad-spectrum antiviral activity of this molecule [64].
Finally, leptomycin B (LMB), a compound isolated from
Chemical structure of compounds that inhibit endocytic pathway and translocation mechanisms.
We have addressed the role of host cells factor and protein inhibition in controlling viral infection. So, we will focus mainly on some important targets of the virus itself. The proteolysis of polypeptide to the 16 NSp is a rate-limiting step in viral replication; thus, it is obvious that targeting viral proteases could achieve significant antiviral activity.
Mpro is one of the best characterized drug targets among coronaviruses. This enzyme is essential for processing the translated polyproteins from the viral RNA. The Mpro works at not less than 11 cleavage sites on the large polyprotein 1ab (replicase 1ab, ~790 kDa); the recognition sequence at most sites is Leu-Gln↓(Ser,Ala,Gly).
The viral replication could be blocked by Mpro inhibitors [65, 66, 67]. There are no human proteases with a similar cleavage specificity. Therefore, these inhibitors are not supposed to be toxic. Peptidomimetic alpha keto-amides were reported to be potential Mpro inhibitors [68]. The natural α-keto amides such as eurystatin A and B, complestatin, and aplidine display prolyl endopeptidase inhibitor, HIV replication inhibitor, and antitumor activity, respectively [68]. Also, theaflavin-3,3′-digallate was reported as natural protease inhibitor in SARS-CoV [9]. Other flavonoids are reported to strongly block Mpro activity such as pectolinarin, rhoifolin, herbacetin [69].
PLpro has dual function, beside its role in release of other nonstructural protein, it neutralizes the immune response by the host cell due its deubiquitinating activity, so its inhibition will not only stop the replication cascade but will help the immune system to regain the ability to recognize and destroy the virus [70, 71]. Hirsutenone, a diarylheptanoid from
Chemical structure of natural compounds that inhibit viral proteases (Mpro and PLpro).
After the transcription of viral RNA to the required structural protein, the hijack of the host cell continues to make many replicas of the viral RNA that will be packed and released. The new virus, RNA helicase was found to be crucial to viral genome replication, which explains why it is a potential target for antiviral drug development. Scutellarin inhibits 90% of SARS-COV RNA helicase activity at 10 μM probably by binding to the ADP active site, myricetin showed the same activity but with much lower extent [75]. Interestingly, ivermectin has shown the ability to inhibit RNA helicase of flavivirus [76], taking in consideration that helicase are structurally conservative among most of the viruses. Ivermectin might also be able to exert the same activity in COVID-19, which in fact may explain the potent antiviral activity addressed previously. Figure 6 shows the chemical structure of the natural helicase inhibitor.
Chemical structure of the natural helicase inhibitors.
One of the hallmarks of late-phase COVID-19 infection is uncontrolled intense release of proinflammatory mediators, which is known as cytokines storm. Different types of viruses tend to activate mitogen-activated protein kinase (MAPKs) cascades, which control proliferation and inflammation in order to stimulate the replication process of the virus RNA. Since the upregulation of MAPKs was linked to several inflammatory and autoimmune diseases, it can lead to multiorgan failure and potentially death.
Clinically, in some patients, it has been reported that their immune response to the SARS-CoV-2 virus results in the increase of cytokines IL-6 and IL-10 [77].
Both hydroxychloroquine and chloroquine have immunomodulatory effects and can suppress the increase of immune factors. Bearing this in mind, it is possible that early treatment with either of the drugs may help prevent the progression of the disease to a critical, life-threatening state. In critically ill SARS-CoV-2-infected patients, the use of corticosteroids may be harmful. While the use of immunosuppressants (e.g., tocilizumab) is not ideal either as it can suppress the immune system and lead to an increased risk of infection. In this setting, hydroxychloroquine may be an ideal drug to treat SARS-CoV-2 infection as it can inhibit the virus via its antiviral effects and help mediate the cytokine storm via its immunomodulatory effects [78].
Fortunately, natural products could serve as the perfect solution in such case as they would not only work as antiviral agents but also could help to downregulate proinflammatory gene and protein expression via affecting a plethora of MAPKs and transcriptional factors. LPS-induced expression of proinflammatory cytokine could be considered as an excellent model for screening, since LPS also activates the inflammatory mediators through several pathways.
For example, diarylheptanoids, flavonoids, and triterpenes, which possess antiviral activity as mentioned earlier, were able to suppress the gene expression of TNF-alpha, IL-1β, IL-6 in different types of cells such as macrophages and HepG2 induced by LPS by modulating multiple intracellular signaling pathways in macrophages and prevent LPS-induced IL-6 production by reducing the mRNA stability via inhibiting ERK1/2 activation. This could be achieved by natural compounds such as flavokawain A, curcumin, quercetin curculigoside, syringic acid or vanillic acid, licochalcone A, chrysin, apigenin, and luteolin at transcriptional level [78, 79]. In brief, the anti-inflammatory effect of natural products is so prominent to be summarized in this chapter, and they can contribute significantly at reducing the mortality rates associated with COVID-19 complications (Figure 7).
Chemical structures for the potential natural immunomodulators for cytokine storm associated with COVID-19 infection.
Therapeutics: AI and ML in treatment discovery development and/or drug repurposing for COVID-19 based on:
EHR data and clinical guidelines
Interaction of human-AI in robotic surgery
Pharmacogenomics for directing the management of medications
AI may contribute to the advancement of resources to support doctors and ultimately enhance medical outcomes. Fuzzy logic can be used in decision support systems to replicate patient decision-making processes [80, 81, 82]. Admittedly, machine learning applied is to clinical data that are regularly collected will produce new knowledge and potentially new perspectives that clinicians lack.
Drug repurposing is hoped to offer a way to establish COVID-19 avoidance and cure policies. For instance, the researchers built a DL approach to classifying current and mercantile medicines for “drug-repurposing,” i.e., identifying a quick treatment using existing medicines that can be introduced to patients immediately. The idea that recently created treatment typically needs years to succeed is reviewed before getting to the public motivates research. Although the results are not accepted clinically, new approaches to combat COVID-19 disease are already opening up [83]. In silico medicine is suggested in [84] using the deep generative model to explore drugs (identifying new medicines). This analysis may be used for simulations and computer modeling to obtain compounds for COVID-19 coronavirus by new molecular entities.
IBM reported that it is now offering an analysis service based on the cloud using the COVID-19 dataset that has been educated [85]. Besides, IBM has implemented its proposed drug discovery AI technology, in which 3000 novel COVID-19 molecules have been produced [86]. In the year 2020, a systematic analysis was developed by Zeng et al. [87] to find drugs for COVID-19. With the support of active Amazon Web Services (AWS), a DL-based model was developed, and 41 data on drug types were validated. As for performance metrics, true-positive rate (TPR), false-positive rate (FPR), etc., have been presented, and the approach suggested by the author is explicit that DL serves as an important instrument for exploring therapeutics.
Earlier, our research team had presented the usefulness of AI and ML in diagnosis of several diseases [88, 89, 90]. However, COVID-19 diagnosis was based on AI.
Multiomics and clinical data
Records of Electronic Health (HER) data and expert knowledge
Nour et al. [91] have developed a DL model for COVID-19 detection, as CNN is applied as a feature extractor. For performance assessment, chest X-ray images dataset is taken into account. For feeding ML methods such as K-nearest neighbour (KNN), Decision Tree (DT), and
Pereira et al. [92] proposed a new model for forecasting the dynamics of COVID-19 that have cases that have happened in other countries or places with similar emission patterns. For all subregions and accessible countries, they implemented a grouping algorithm.
Big data in the administration of hospitals, epidemiology, insurance, medication interactions and complications, outcomes reviews based on quality, epidemic tracking.
Speech datasets include breath sounds and cough, which can be utilized for COVID-19 diagnoses and its prediction for illness seriousness. Machine learning, statistical techniques, and big data may be used to the datasets for prediction functions about the disease. Various open-source datasets for COVID-19 included mobility, diagnosis, contagion assessment, NPI analysis, statistic relationships, and sentiment analysis.
COVID-19 causes a gigantic load to the healthcare system, particularly in patients with preexisting conditions comorbidities. A comprehensive study is presented about COVID-19 symptoms, clinical classification (mild, moderate, severe, critical cases), and the risk indicators for COVID-19 infection with comorbidities.
Natural products (NPs) have been used for centuries for treatments of different maladies and inspired scientists to develop safer and more effective drugs. The COVID-19 is complex clinical condition that comprises inflammatory components. Although selective inhibitor could be developed for inhibiting critical molecular target in the life of cycle, compounds with multitargeting activity may be more favorable to reduce the possibility of mutation development. Optimum drug should be able to modulate host cell and viral-related mechanisms. This is where natural products could play important role since their ability to bind effectively to targets with completely different homology. Nevertheless, the anti-inflammatory attribute of NPs is another advantage that should be considered during choosing therapeutic protocol. Finally, the observed antiviral activity of different phytochemicals should initiate repurposing campaign of untested NPs to identify new antiviral compounds, which could be exploited to design more effective drugs with optimum pharmacokinetic properties. This study presents briefly the value of AI and ML as powerful tools in healthcare, clinical, drug industry, diagnosis, decision-making, and improvement of the selection criteria for the most appropriate protocol for the treatment of COVID-19.
The author would like to thank Ms. Rowida Omar (Department of Pharmacognosy, Faculty of Pharmacy, Delta University, Gamsa, Egypt) and Mr. Abdullah A. Elgazar (Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University, Egypt) for their great efforts in providing valuable materials of the first draft and Mrs. Zahraa Tarek (Computer Science Department, Faculty of Computer and Information, Mansoura University, Egypt) for providing materials on artificial intelligence section.
The authors declare no conflict of interest.
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Where a reservoir is located near an active volcano, the sedimentation will be very severe. Wlingi and Lodoyo reservoirs are severely affected by eruptions of Kelud volcano, one of the most active volcanoes in Indonesia. After the February 2014 eruption, the capacity of Wlingi and Lodoyo reservoirs decreased dramatically to 2.20 million cubic meter (Mm3) and 1.33 Mm3, respectively, just 46 and 49% of their pre-eruption capacities and 19.42 and 26.60% of their initial capacities. To cope with the extreme sedimentation problems in Wlingi and Lodoyo reservoirs, diverse sediment management strategies have been applied in these reservoirs and their catchments. Construction of many on-stream sediment control facilities (sabo works) and a sediment bypass channel has reduced sediment inflow to the reservoirs. Removal of deposited sediment by dredging and hydraulic flushing in Wlingi and Lodoyo reservoirs has also resulted in storage capacity recovery. These measures are an integral part of the Mt. Kelud Volcanic Disaster Mitigation Plan.",book:{id:"6189",slug:"sedimentation-engineering",title:"Sedimentation Engineering",fullTitle:"Sedimentation Engineering"},signatures:"Fahmi Hidayat, Pitojo T. 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This study examines the role of sedimentary processes in sediment distribution in the various geologic environments. The outcrop sections and the Afikpo River were studied by visual observation and photographing of important features during a field mapping exercise. Well log data from the Niger Delta Basin were also used to infer depositional environments based on gamma ray log motifs. These outcrop sections consist of fluvial, deltaic and shallow marine sediments that occurred as braids, point-bars, mouth-bars and beach/regressive bars. Braids and point-bar deposits also occurred within the recent Afikpo River channel, a major conduit transporting sediments to the offshore area of eastern Niger Delta. Sandstone outcrops showing a mouth-bar architecture occurred at Akpoha Town east of Afikpo Town, with a shallow marine sequence at Amasiri area, west of Afikpo Town. The Amasiri sandstone is a massive outcrop with large lateral extent covering more than 8 kilometers. 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He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. 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He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. 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His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"41",type:"subseries",title:"Water Science",keywords:"Water, Water resources, Freshwater, Hydrological processes, Utilization, Protection",scope:"