\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Mobilization activities provide the living organism with a better quality of life. Hence, smart mobilization of human beings is also the key activity to increase the standard of living to a higher state.
\r\n\r\n\tThe aim of this book is to clearly provide a comprehensive overview of the state-of-the-art on various topics in smart mobility from various perspectives. Beginning with the need for mobilization, issues, and challenges throughout the world, new solutions and the blueprint to support smart cities’ development can be discussed. In addition, the governmental perspectives of smart mobility implemented throughout the globe will be discussed and explained. Smart technology including sensors, instrumentation, cyber physical system, and internet of things will be introduced to apply the cutting edge technology inside smart mobility systems. Besides, the application of artificial intelligence and machine learning including image processing and digital signal processing methods will be discussed to provide better results in implementing big data analysis. On the other hand, smart mobility for special needs persons such as persons with disabilities (PWDs) is also one of the criteria to be fulfilled by considering accessibility and a barrier-free universal design when developing the infrastructure.
\r\n\r\n\tThis book intends to provide the reader with the impact and the future of smart mobility in terms of sustainability, social, environmental and economic impact needed to develop smart mobility infrastructure.
",isbn:"978-1-80355-712-0",printIsbn:"978-1-80355-711-3",pdfIsbn:"978-1-80355-713-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"dfbb68888e2eceead2512c37f1f6bce9",bookSignature:"Dr. Arif Sarwat, Ph.D. Student Asadullah Khalid and Dr. Ahmed Hasnain Jalal",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11189.jpg",keywords:"Implementation, Sensor, Cyber-Physical System, Internet of Things, Artificial Intelligence, Machine Learning, Image Processing, Digital Signal Processing, Mobility Need, Accessibility, Special Needs, Environmental Impact",numberOfDownloads:52,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 12th 2021",dateEndSecondStepPublish:"December 22nd 2021",dateEndThirdStepPublish:"February 20th 2022",dateEndFourthStepPublish:"May 11th 2022",dateEndFifthStepPublish:"July 10th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"6 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Arif Sarwat has been in the industry (Siemens) and academia for more than 20 years. He has published more than 200 peer-reviewed articles and multiple patents. He currently has multiple funded projects, funded by the NSF, industry and the DOE",coeditorOneBiosketch:"Dr. Asadullah Khalid obtained his Ph.D. degree in Electrical and Computer Engineering from the Florida International University, Miami, FL, USA. His research interests include battery management systems, microgrids, applied machine learning, and energy storage cybersecurity.",coeditorTwoBiosketch:"Dr. Ahmed Hasnain Jalal: Ahmed Hasnain Jalal is a Visiting Assistant Professor in the Department of Electrical Engineering at the University of Texas Permian Basin. He earned his Ph.D. and MS from Florida International University and Purdue University Northwest in 2018 and 2010, respectively.",coeditorThreeBiosketch:"Dr. Ahmed Hasnain Jalal: Ahmed Hasnain Jalal is a Visiting Assistant Professor in the Department of Electrical Engineering at the University of Texas Permian Basin. He earned his Ph.D. and MS from Florida International University and Purdue University Northwest in 2018 and 2010, respectively.",coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"440920",title:"Dr.",name:"Arif",middleName:null,surname:"Sarwat",slug:"arif-sarwat",fullName:"Arif Sarwat",profilePictureURL:"https://mts.intechopen.com/storage/users/440920/images/system/440920.jpg",biography:null,institutionString:"Florida International University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Florida International University",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:{id:"440783",title:"Ph.D. Student",name:"Asadullah",middleName:null,surname:"Khalid",slug:"asadullah-khalid",fullName:"Asadullah Khalid",profilePictureURL:"https://mts.intechopen.com/storage/users/440783/images/system/440783.png",biography:null,institutionString:"Florida International University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:{id:"440934",title:"Dr.",name:"Ahmed Hasnain",middleName:null,surname:"Jalal",slug:"ahmed-hasnain-jalal",fullName:"Ahmed Hasnain Jalal",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:"Department of Electrical Engineering, University of Texas Permian Basin",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:[{id:"80518",title:"Intersection Management, Cybersecurity, and Local Government: ITS Applications, Critical Issues, and Regulatory Schemes",slug:"intersection-management-cybersecurity-and-local-government-its-applications-critical-issues-and-regu",totalDownloads:46,totalCrossrefCites:0,authors:[null]},{id:"82256",title:"Parent Opinions of Automated Vehicles and Young Driver Mobility",slug:"parent-opinions-of-automated-vehicles-and-young-driver-mobility",totalDownloads:6,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429343",firstName:"Martina",lastName:"Ivancic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/429343/images/19998_n.jpg",email:"martina@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"52448",title:"THz QCLs Design Toward Real Applications",doi:"10.5772/65351",slug:"thz-qcls-design-toward-real-applications",body:'\nThe terahertz (THz) region in the electromagnetic spectrum has drawn much attention due to its wide range of applications in various fields such as spectroscopy, imaging, remote sensing, and communications. Compact THz semiconductor sources are also extremely promising for use in future high‐speed and large‐capacity local telecommunications applications, especially for those applications operating in the range from sub‐THz to a few THz (0.2–2 THz) [1]. The output power of conventional mature radio frequency (RF) electronic devices reduces by 4 orders of magnitude with frequency, which is close to 1 THz in the order of a few microwatts (µW). High‐output‐power continuous‐wave (CW) operation of optical semiconductor devices is very attractive for overcoming this problem. Quantum cascade lasers (QCLs) [2] are compact semiconductor light sources that utilize carrier recycling and intersubband transitions in repeating quantum well (QW) structures, and they have been demonstrated to operate successfully in the mid‐infrared (mid‐IR) [2] and THz [3] regions. They are also arguably the only THz solid‐state sources with average optical output power levels much greater than one milliwatt (mW). This property of high optical output power with a narrow emission line width is quite attractive for a wide range of THz applications.
\nThe current status of THz QCLs that operate without an external magnetic field has been reported in the spectral range from 1.2 to 5.2 THz [4, 5] with a maximum output power of around 1.01 W in pulsed mode [6]. In contrast to the room temperature operation of mid‐IR QCLs, the maximum operating temperature (
On the basis of some successful solutions in mid‐infrared QCLs, the different barrier height shows some solution to improve the device performance for different directions. For example, utilizing the height barriers to reduce the high temperature parasitic leakage currents [9, 10] and step wells for improving internal quantum efficiencies [11]. Furthermore, with the high technique of crystal growth, the optimization of the individual barrier and well\'s height at the suitable place is possible to give the solution and one more design freedom of recent stagnated structure design of THz QCLs. Considering these research and our previous studies on high Al composition AlxGa1_xAs/GaAs design [9], it indicates one of the possible directions for combining the high Al composition structure with variable well‐barrier height design [12] in order to achieve the thermoelectric cooling and higher temperature operation of THz QCLs. For this kind of modulation well‐barrier height modulation height active structure. It is also expected to utilize the further indirect injection design.
\nThe recent two methods are introduced for improving the performance of THz QCLs. We demonstrate a relative compact‐size semiconductor THz source unit by the recent fabrication of THz QCL devices for real applications. The operation temperature largely limited the real compact size potable THz applications by semiconductor‐based QCLs. A compromise solution is to capitalize on the liquid nitrogen (LN2) cooling Dewar condenser, keep the useful characteristics of THz QCLs and reduce the cooling system size, and realize the robust portable compact size THz source unit by QCLs. The output power is one of the most important characteristics required for the different real THz applications. The recently large peak output power THz QCLs are realized by a large size mesa with a semi‐insulated surface plasmon (SI‐SP) waveguide and achieved the 1 W peak power. But this still limited on the pulse operation, the average output of THz QCLs still recorded by the previous report [13]. Here, we introduce a Dewar condenser cooling system with our recent fabricated metal‐metal waveguide (MMW) modulation height active structure THz QCLs and the premier measurement results of few microwatts average power with milliwatt order peak power, larger output power THz QCLs with the peak output power of 250 mW and the average output power of 2.2 mW, indicating the further improvement in the direction of the continuous‐wave (CW) mW order average power operation. In the following paragraphs, we introduce the details of indirect injection low frequency THz QCLs, modulation height active structure design, and a Dewar condenser type THz source unit by THz QCLs.
\nAn indirect injection scheme was first reported for mid‐IR QCLs among the different kinds of injection schemes [14]. Illustrative band diagrams of typical resonant tunneling injection schemes are shown in Figure 1: (a) for a simplified three‐level system and (b) for a simplified four‐level indirect scattering‐assisted injection scheme with diagonal THz emission, which is used in this work. Improvements in performance have been successfully achieved using fast and smooth LO phonon injection without carrier accumulation. This injection scheme is also expected to circumvent the limitations of the RT injection scheme and to enable the realization of low‐frequency THz QCLs operating at high temperatures. However, the much larger radiative energy in the mid‐IR region causes different subband transport characteristics that need to be considered in designs for THz frequencies. It is difficult to implement an indirect injection design with the correct carrier injection and narrow radiative energy at THz frequencies. Even this design scheme still suffers difficulties in the THz region compared with mid‐IR QCLs. After several theoretical proposals [15–17], a few recent experimental reports [8, 18–20] of indirect injection designs show promising results and demonstrate that there is high potential for attaining low‐frequency, high‐temperature THz QCLs.
\nHere, we demonstrate an Al0.175Ga0.825As/GaAs QCL design that uses a combination of indirect injection and a less vertical diagonal for emission in the THz region. Structures were grown on semi‐insulating GaAs (100) substrates by solid‐source molecular beam epitaxy (MBE). The growth sequence started with a 250‐nm‐thick Al0.6Ga0.4As etch‐stop layer. The active/injection layers, which are sandwiched between two 100‐nm‐thick
Illustrative band diagrams of (a) resonant tunneling injection scheme with subband alignment and (b) indirect scattering‐assisted injection scheme with diagonal THz emission.
In practice, this kind of simplified four‐level indirect injection scheme depends mainly on the external electrical field. Figure 2 shows the dependence of the energy separation of the subbands on the external electric field for our structure. In the low electric field region around 12–14 kV/cm, the energy separation and band‐diagram conditions are similar to the conventional RT injection scheme, as shown in Figure 3(a): it shows a simplified three‐level‐type design including two lasing levels and one injection level with a subband alignment injection process; the band diagram related to this is shown in Figure 1(a). The injection process occurs from
Calculated energies of the subband levels in the band diagram of the designed structure with respect to the external electric field. Region 1 is similar to conventional THz QCLs using the RT injection scheme, with a radiative energy of around 5 THz. Region 2 is for the indirect injection scheme combined with diagonal emission with a radiative energy below 2 THz.
We focus only on the realization of a radiative process at high electric fields for 1.9 THz lasing. This occurs in the range of 17–19 kV/cm, as shown in Figure 2, which is related to the designed band diagram presented in Figure 3(b). Here, we utilize the LO phonon scattering process to selectively inject carriers from previous injection/extraction levels (
Self‐consistent calculations of the conduction band diagrams of the
This combination of injection with the emission process also overcomes the critical injection barrier thickness in the RT injection scheme, and achieves a wider dynamic range for the operating current density. In the RT injection design, the dynamic range of the operating current density is related to the emission energy of the QCLs because the resonant condition for lasing corresponds to the subband alignment from
When we replace the injection process by a scattering process, as shown in Figure 1(b), the injection from
Here, we demonstrate 1.9 THz Al0.175Ga0.825As/GaAs QCLs with
In order to design the further indirect injection THz QCLs with more design freedom in narrow energy THz frequency, which traditionally usual suffered from opposite thickness optimization. Here, we introduce the active structure design with different heights of barriers and wells. First, we present primary experimental results by arranging the recently recorded three‐well resonant tunneling structure design; modulate the Al the height of barriers with the different emission barrier compositions and introduce an external thin barrier in the widest extraction/injection well. This modulation barrier THz QCL sample succeeds lasing at 3.7 THz with the maximum operation temperature of up to 145K.
\nCurrently, the best performing designs are mainly based on the resonant phonon depopulation scheme for extraction utilizing the AlGaAs/GaAs material systems with one kind of Al barrier concentration 15%. The modulation Al composition barrier THz QCL samples are grown by solid‐state MBE with multiple Al cells. The thickness and Al compositions are precisely controlled within 1% difference. Then the devices are fabricated in the Cu‐Cu metal‐metal waveguide by photolithograph and dry etching. The active region structure design and band diagram are shown in Figure 4.
Band diagram of our modulation barrier THz QCLs in this paper. Based on the three‐well resonant tunneling design and arranged with one external thin barrier and lower emission barrier.
First, we follow the three‐well resonant tunneling injection design [7], achieve diagonal emission and increase the spatial separation between upper and lower lasing levels in order to reduce the parasitic injection leakage comes from nonradiative thermally activated longitudinal phonon scattering at high temperature operation. At the widest extraction/injection well, we expected to add an external thin and high layer in order to improve extraction by interface roughness (IR) scattering, which is one solution used in mid‐infrared QCL design [25]. The simulated Al composition of this external barrier with an amount of IR scattering, oscillator strength between the extraction/injection level (
Simulation of external barrier Al composition with the amount of IR scattering, oscillator strength between the extraction/injection level (
For the further design, we also would like to increase all the barrier compositions, so here we first keep this thin barrier composition the same with others barriers at 15%. The lower emission barrier between two emission wells is modulated in order to reduce the nonradiative IR scattering at the emission layers. The Al composition of the emission barrier with the amount of IR scattering and oscillator strength between two lasing levels (
Simulation of emission barrier Al composition with the amount of IR scattering, oscillator strength between two lasing levels (
We utilize the lower emission barrier to reduce the IR scattering at the emission region, add an external thin barrier to improve the injection efficiency and reduce plastic leakage current from
After introduce the recent fabricated THz QCLs toward high temperature operation at low frequency (<2 THz) and the 3–4 THz region. For THz applications, the output power is more critical than the operation temperature. Even the recent devices cannot operate at the room temperature. Utilizing some kinds of cryogenic systems, it is still possible to achieve the relatively compact size potable THz application by THz QCLs. Here, we introduce the liquid nitrogen Dewar condenser to combine the fabricated THz QCLs as mentioned above. The size of Dewar is 14 cm2 with 28 cm high without the outside external power supply (Figure 7(a)), the QCL sample array (Figure 7(c)) is fixed under vacuum conditions with cooling holder direct cooled by heat conduction from LN2. The QCL samples are combined with hyperhemispherical Si lens in front of operated mesa and an adjustable inside parabolic mirror in order to focus the output of THz QCLs (Figure 7(d)) and give the near collimated THz wave outside the measurement Tsurupica windows from the widely diverged MMW QCLs.
(a) The photograph of the Dewar condenser. (b) Far‐field pattern of the Dewar condenser measured using NEC THz camera IR/V‐T0831. (c) The photograph of fabricated THz QCL array with 9 mesas. (d) The fixed QCL array with hyperhemispherical Si lens and an adjustable parabolic mirror inside.
In our case, without the hyperhemispherical Si lens, the far‐field pattern angle of MMW QCLs is about 40°. If coupled with the Si lens, it is possible to adjust the maximum output near 0°. This is very helpful for the adjusting the THz wave from the small size measurement window and use for real applications. The far‐field pattern is also shown in Figure 7(b), which measured using the NEC THz camera IR/V‐T0831. The adjustment of the position of Si lens is also quite important for the increasing the output power, with and without the Si lens, the measured out power can be increased about 2.5–3 times. The active region design is based on the four well‐resonant tunneling injection LO depopulation scheme with the variable barrier height modulation active structure THz QCLs as discussed above, which originally toward the high temperature operation. The waveguides also use the high temperature operation MMW. The output peak power is 0.1 mW with a duty cycle of 0.02% (1 kHz repeated frequency with 200 ns pulse width). When the duty cycle increases to 5% (10 kHz repeated frequency with 5 µs pulse width), the device gives the 37 µW average power with >1 mW peak power. The changes in duty cycle by changing the repeated input pulse frequency and pulse width are related to the peak output power of THz QCLs when the pulse width is below 1 µs. The too short pulse did not supply the enough input energy for devices. The peak power is become stable when the input pulse is larger than 1 µs. But the average power can be increased continuously with the increasing duty cycle.
\n\nRecently, our stable pulse generator (AVTECH AVO‐6HZ‐B) with impedance match can only operate up to 5%. The device can possibly operate at higher duty cycle with larger average output power. But when the duty cycle increases, the heat generated from the device is quite large during the operation, comparing with the measurement condition 0.02%, even with the use of continuous flow liquid helium cryostat. The device heat sink temperature is increased up to 30 K during the operation. For the Dewar case, the duty cycle is larger than 1%. The recent contact electrode by indium ball and 0.07 mm‐thin cupper wire for electric connection is easy to be melted. It causes the difficulty for stable CW operation. The measurement spectrum and the stable operation of current density‐voltage, current density‐light output characteristics direct from the Dewar condenser, are shown in the inset of Figure 8. We can find that the Dewar gives the clear single color 3.8 THz lasing spectrum, stable milliwatt order peak power and microwatts order average power. The maximum peak power is 3.1 mW and maximum average power is 6.2 µW under recent Dewar setting conditions.
\nThe measurement lasing spectrum and the stable operation of current density‐voltage, current density‐light output characteristics direct from the Dewar condenser.
For the CW operation with milliwatt average output power, the improvement for the recent Dewar system mainly obtained by two directions: first is the THz QCL device, recently the QCLs used in this condenser are toward the high temperature operation MMW QCLs with narrow ridge width and small mesa size. The output performance of THz QCLs generally decreases when the operation temperature is above 100 K. Upon cooling with the LN2, the performance do not dramatically change to a large extent under low temperature conditions. The few tens K temperature operation is not important for this Dewar setting. The device fabrication move to the larger mesa size SI‐SP waveguide can improve the output performance with the better far‐field pattern. It is suitable for the high output 77 K Dewar condenser with the easier optical aliment in applications. Second direction is the improvement and consideration of cooling efficiency of the Dewar condenser. The recent operation duty cycle is limited by the wire connection and the electrode of the mounted sample holder not by the device itself. If we can reduce the temporary heat increase with large duty cycle by wide size heat conduction and good thermal conductivity, it is possible to improve the operation duty cycle of the Dewar condenser.
\nOn the basis of the first direction, we introduce the recent fabricated modulation active structure THz QCL cooling and setting with the active structure design by more vertical emission and large current injection. This way we achieve the large output THz QCLs with a peak power of 250 mW and an average power of 2.2 mW under the condition of duty cycle 1%. L‐I‐V characteristics, lasing spectrum, and far‐field pattern measured using THz camera are shown in Figure 9. The LN2 Dewar condense demonstrated as a robust compact size THz source unit with stable milliwatt order peak power and microwatts order average power operation by THz QCLs. And the large output power devices without high temperature operation (>100 K) also show the potential for the more powerful THz source unit toward the target of CW operation with milliwatt average output power. For further improvement of Dewar condenser, we replace the recent fabrication by SI‐SP waveguide with large mesa size and high output power active region design, increase the current duty cycle limitation comes from the power supply, cooling efficiency of connect wire and electrode.
\nThe measurement of (a) current density‐voltage, current density‐light output characteristics, (b) lasing spectrum, and (c) far field pattern of large output THz QCLs.
Here, we discuss the design and fabrication of THz QCLs toward the high temperature and large average output power operations for the real THz applications with the relatively compact portable size cryogenic cooling systems. We also describe the temperature performance parameters of THz QCLs, introduce the results of an indirect injection design scheme in the THz region and modulation height active structure design with different barriers and wells for further design direction. The recent fabricated THz QCLs are combined with the liquid nitrogen cooling Dewar condenser to demonstrate the relatively compact potable THz source unit by QCLs. The different injection schemes in THz and barrier‐well height design in the active region introduce one of the directions for the further high temperature and large output power operation of THz QCLs for real applications.
\nVitamin D plays an important role in calcium and phosphorus metabolism, which are essential for bone health and various biological functions. In vitamin D deficiency, clinical and biochemical rickets characterized by hypocalcemia (irritability, fatigue, muscle cramps, seizures), hypophosphatemia and skeletal manifestations (delayed closure of fontanelles, craniotabes, frontal bossing, bowed legs, enlarged wrists, bone pain, and short stature) in children and adolescents or osteomalacia in adults may occur. Over the past several decades, it has been reported that the efficiency of vitamin D is not limited only to maintaining bone health by managing the calcium homeostasis, but also seems to have anti-inflamatory, immune-modulating and pro-apopitothic properties [1]. There are two different precursor molecules of vitamin D. The first is vitamin D3, or cholecalciferol, which is the main source of vitamin D in the body and is synthesized from the skin by exposure to sun. Vitamin D3 can also be obtained from dietary animal foods (fish, egg yolks) or medicines (vitamin supplements). The second precursor is vitamin D2, or ergocalciferol, which can be used as a source of vitamin D via oral medication or through enriched foods. Vitamin D3 differs in molecular structure from vitamin D2 in that it has a double bond between the 22nd and 23rd carbon atoms and a methyl group on the 24th carbon atom [2]. These structural differences in vitamin D2 affect its catabolism. Compared to vitamin D3, vitamin D2 has a lower affinity for vitamin D-binding protein (VDBP), which leads to its easy removal from the circulation, a reduced formation of 25-hydroxy vitamin D2 (25OHD2) by the 25-hydroxylase enzyme, and increased inactivation by the action of 24-hydroxylase [3, 4, 5]. Although both vitamin D2 and D3 are used as drugs, studies have shown that a higher serum 25OHD2 vitamin level is obtained when vitamin D3 is used in treatment compared to vitamin D2 [6]. In addition, it has been shown that active vitamin D obtained from vitamin D3 has a higher affinity for the vitamin D receptor (VDR) [4]. Despite these differences, vitamins D2 and D3 are both metabolized in substantially the same way and are commonly referred to as vitamin D. Vitamin D is a prohormone and inactive, and to be activated, it must go through a series of enzymatic and non-enzymatic steps.
Formation of vitamin D3, which is the first step of vitamin D synthesis, takes place in the epidermis by a non-enzymatic process (Figure 1). Vitamin D3 is the most important source of vitamin D in the body. 90–95% of vitamin D3 in the human body is produced from the skin with the effect of sunlight. Therefore, sunlight is the main source of vitamin D synthesis, and if there is sufficient exposure to sunlight, there is no need to take additional vitamin D. The mechanism of non-enzymatic photolysis of vitamin D by ultraviolet B (UVB) rays with wavelengths in the range of 290–315 nm involves the breaking of a bond in the B ring of 7-dehydrocholesterol (pro-vitamin D3), resulting in pre-vitamin D3 formation in the epidermis. Subsequently, two different double bonds are formed between the broken carbon atoms in the B ring by thermo-sensitive non-enzymatic process, and the formation of vitamin D3 from pre-vitamin D3 is completed (Figure 2) [7].
Vitamin D metabolism.
Vitamin D3 synthesis from 7-dehydrocholesterol in the epidermis.
The synthesis of vitamin D3 from pro-vitamin D3 in the skin is adjusted according to the needs of the organism. In a period of just fifteen minutes, pre-vitamin D3 is synthesized from pro-vitamin D3 with the effect of ultraviolet light. Conversion from pre-vitamin D3 to vitamin D3 occurs by isomerization in a rather slow and thermo-sensitive manner. In the case of exposure to UV rays or solar radiation for a long period, pre-vitamin D3 converts to a number of photolyzed inactive by-products, such as lumisterol (irreversible) or tachysterol (which can be converted back to pre-vitamin D3). These by-products have no biological effects (Figure 2). In other words, once pre-vitamin D3 is formed in the skin, it turns into either vitamin D3 or inactive metabolites. This is a physiological control mechanism that protects the body from vitamin D intoxication by preventing unnecessary vitamin D synthesis [8, 9].
Some conditions that prevent UVB rays from reaching the skin cause a decrease in vitamin D production. One of these reasons is the ozone (O3) layer surrounding the atmosphere, which reflects some of the sun’s rays, preventing them from reaching the Earth and their harmful carcinogenic effects on the skin. The peak UVB wavelength required for optimal vitamin D synthesis from the skin is 297 (290–315) nm [1, 8]. In addition, air pollution, aerosols, water vapors, and increased nitrogens in the air also play a role in preventing sunlight reaching the Earth, and consequently result in a potential reduced synthesis of vitamin D [8]. Another factor affecting the effectiveness of UVB rays in the synthesis of vitamin D in the skin is the solar zenith angle, which affects how UVB rays reach the world quantifiably. When the sun moves in a path closer to the horizon, which occurs in the northern latitudes in the winter season, vitamin D synthesis is more adversely affected (or reduced). In the summer time in the northern latitudes, a normal biosynthesis is more propitious or favorable. The narrowing of this angle indicates that the sun rays reach the Earth more steeply and intensely. The solar zenith angle is closely related to sunbathing time during the day, the seasons and the geographic region (latitude). Sunlight reaches the Earth most intensely in the “mid-day” when it is summer in the northern latitudes and the weather is clear. Finally, it is thought that sunlight exposure is sufficient for vitamin D synthesis in all geographic regions below 35 degrees north or south latitude all year round. In regions beyond this latitude toward the poles, especially in winter, sunlight is not sufficient for vitamin D synthesis. For example, UVB rays are not sufficient for vitamin D synthesis between October and April in Rome, which is located on 41.9 degrees north latitude, and between November and February in Berlin and Amsterdam, which are located on 52 degrees north latitude. For the reasons mentioned above, it is difficult to predict how much UVB rays reach the skin and how much of this increases serum vitamin D levels. In experimental studies, it has been reported that UVB rays that will cause minimal erythema in 25% of the skin are equivalent to 1000 units of oral vitamin D intake [2, 3, 8].
UVB rays are also affected by the individual’s clothing style, use of sunscreen, and skin colour determined by pigmentation with melanin. In dressing style, especially the type of the clothing fabric used is of great importance [10]. Non-synthetic, light-colored, and linen garments play a less preventive role in UV rays reaching the skin than do garments made of silk, nylon, polyester, and wools. For example, black-dyed cotton clothing prevents 98.6% of UVB rays from reaching the skin compared to white (undyed) cotton clothing, which blocks 47.7% of UVB. Topical sunscreens also prevent UVB rays from reaching the skin by absorbing, reflecting or dispersing them. Topical creams with a sun protection factor of 8 or higher block vitamin D synthesis above 95% [11]. Melanin is a large, opaque polymer synthesized by melanocytes in the skin through the stimulus of exposure to UVB rays. Melanin competes with dehydrocholesterol 7 in the skin to absorb UVB photons and thus inhibits vitamin D synthesis [12]. Individuals with dark skin colour have more melanin pigment in their epidermis than light-skinned individuals and require higher concentrations of sunlight for the same amount of vitamin D synthesis [12]. In addition, the 7-dehydrocholesterol level (provitamin D) in the epidermis can also affect the serum vitamin D concentration. For example, 7-dehydrocholesterol levels in scar tissue caused by the burn are reduced by 42.5% of normal. In these cases, progressive vitamin D deficiency develops, especially if supplemental dietary vitamin D is not provided. Moreover, the content of provitamin D in the skin decreases with age. Skin temperature is also important for vitamin D synthesis. Vitamin D from pre-vitamin D by isomerization whose rate of formation is temperature- dependent. The rate decreases as the skin temperature decreases. In a healthy person, the skin temperature is lower than the central body temperature and varies between 29 and 35 degrees Celcius. When the skin temperature is 37 degrees Celcius, the isomerization of vitamin D from pre-vitamin D occurs within 2.5 hours [13, 14].
Vitamin D3 synthesized in the skin is released into the systemic circulation and all forms are transported by binding to VDBP in serum. A portion of vitamin D, a fat-soluble vitamin, is stored in adipose tissue for use when necessary. The ability of vitamin D to be stored in adipose tissue extends its total half-life in the body up to approximately 2 months. When vitamin D3 is transported to the liver, it is first converted into 25OHD3 by the cytochrome P450 25-hydroxylase enzyme. 25OHD3 is the main circulating form of vitamin D, and it is the parameter that provides the best estimation about the body’s vitamin D pool [15]. Various enzymes that show 25-hydroxylase properties have been described in the body. Among these, the first one is CYP27A1 located in mitochondria, and the second is microsomally located CYP2R1 [1, 6, 16]. CYP27A1 also exerts 27-hydroxylase effect and is involved in bile acid synthesis. Although CYP27A1 is expressed in different tissues of the body, the tissues where it is most commonly found are liver and skeletal muscle tissues [1, 2]. In experimental studies, it was reported that the serum 25OHD3 levels were increased in mice which possess an inactivated CYP27A1 gene, and that rickets did not occur in these mice [17]. Interestingly, in this study, it was shown that CYP2R1 expression increased after CYP27A1 gene inactivation, and consequently 25-hydroxylation activity increased [17]. In addition, individuals with a CYP27A1-inactivating mutation develop a cerebrotendinous xanthomatosis disease with bile and cholesterol synthesis disorders, but without rickets manifestation [18]. Besides CYP27A1, different CYP-450 enzymes with 25-hydroxylase activity (CYP2D25, CYP2J2, CYP2J3, and CYP2C11) have been identified in humans and animals, with the most important one in human being CYP2R1. It is assumed that enzymes other than CYP2R1 have effects only on serum 25OHD3 levels [2].
Studies have suggested that CYP2R1 is the major enzyme responsible for 25-hydroxylation in the human body. This enzyme is expressed in many tissues, mainly liver, skin, and testis [1, 2, 17]. The 25-hydroxylase encoded by the CYP2R1 gene was first described by Cheng et al. [19]. It was first reported by Chen et al. [20] that homozygous inactivating mutations of this gene lead to clinically observed rickets (vitamin D-dependent rickets type IB) in Nigerian families. It has been reported that these cases gave suboptimal response to standard vitamin D (inactive vitamin D2 or D3 forms) treatment [21]. The CYP2R1 enzyme has equal affinity for the different forms of vitamin D precursors (D2 or D3) [19]. Studies have shown that 25-hydroxylase effect increased in male rats given estrogen, whereas this activity decreased in female rats given testosterone [21]. Despite experimental studies, the effect of sex steroids on 25-hydroxylase enzyme activity in humans is unknown. It has been shown that in CYP2R1-null mice, the level of 25OHD3 decreases by 50%, when both CYP2R1 and CYP27A1 are inactivated, and that serum 25OHD3 levels decrease by 70%, and serum 25OHD3 level remains at a measurable level in both cases [2, 17]. This supports the view that serum vitamin D level is compensated by other enzymes with recruitable 25-hydroxylase enzyme activity.
The final step of active vitamin D formation takes place in the proximal tubules of the kidney, led by the enzyme 1-alpha hydroxylase. 25OHD3, which is bound to VDBP, is taken into tubule cells and metabolized (1-alpha hydroxylation) through megalin and cubilin, which are transmembrane proteins located in renal tubules and act as surface receptors for VDBP in tubules. 25OHD3, which then undergoes 1-alpha hydroxylation [1, 2]. The 1-alpha hydroxylase enzyme hydroxylates the first carbon atom in the A ring of 25OHD3, resulting in the formation of 1,25 (OH) 2D3 [1]. CYP27B1 is the only enzyme that has 1-alpha hydroxylase activity. This enzyme, which belongs to the cytochrome P-450 enzyme system, is located in the inner mitochondrial membrane and carries out electron transport to NADPH via ferrodoxin-ferrodoxin reductase [1, 2]. The gene for the enzyme consists of nine exons and is located 12q14.1 chromosomal region. Four different groups reported the cloning and sequencing of the gene from rats, mice and humans [22, 23, 24, 25, 26]. In biallelic inactivating mutations of this enzyme, which is highly homologous to some mitochondria located cytochrome P-450 enzymes (CYP27A1 and CYP24A1), 25OHD3 cannot be converted to 1.25 (OH) 2D3, which is the active vitamin D form. In this case, the clinical picture of vitamin D-dependent rickets type 1A (also called pseudo-vitamin D deficiency rickets) occurs [23]. This disease is typically characterized by rickets, with clinically observed very low 1.25 (OH) 2D3, low serum calcium/phosphorus, and high parathyroid hormone (PTH) levels. CYP27B1 is expressed mainly in the renal proximal tubules and in the placenta during pregnancy [27]. While the expression of the gene encoding this enzyme increases with the effect of PTH, it decreases with FGF23 (fibroblast growth factor 23) and 1.25 (OH) 2D3. CYP27B1 gene is also expressed in lung, brain, breast and intestinal system epithelial cells, immune system cells (macrophage, T/B lymphocytes and dendritic cells), osteoblasts, chondrocytes, and some tumor cell types [1, 2]. The regulation of the extra-renal localized 1-alpha hydroxylase enzyme differs. In some granulomatous diseases where monocyte/macrophage cells play an important role (sarcoidosis, tuberculosis, Chron’s disease, etc.), with the effect of IL-1, TNF-α, IFN-γ, 1-alpha hydroxylase enzyme activity increases and 1,25 (OH) 2D3 is synthesized in greater quantities than normal, and consequently, hypercalcemia and hypercalciuria emerge [28, 29, 30]. Additionally, since cells in these tissues do not have PTH receptors, it is not yet understood how PTH exerts its enhancing effect on the 1-alpha hydroxylase enzyme activity in these cells. In one study, it has been suggested that this enhancing effect of PTH may have occurred through post-transcriptional effects [31]. Moreover, 1-alpha hydroxylase enzyme in these cells is not inhibited by 1,25 (OH) 2D3 or hypercalcemia, unlike the renal tubules.
The 24-hydroxylase enzyme is located in the mitochondrial inner membrane of the cells located in the proximal kidney and, like CYP27B1, uses the electron transport system that enables electron transport to NADPH via ferrodoxine-ferrodoxin reductase. It is known that CYP24A1, which is the only enzyme showing 24-hydroxylase enzyme activity in humans, can also exhibit 23-hydroxylase enzyme activity [2]. Which enzyme will be more prominent varies according to the species [32]. The 23-hydroxylase, another enzyme that degrades vitamin D, is the first step activity in the conversion of 1,25 (OH) 2D3 to 1,25 (OH) 2D3-23,26-lactone.
The CYP24A1 enzyme, encoded in 20q13 chromosomal region and having 24-hydroxylase enzyme activity, initiates catabolic processes that lead to the inactivation of vitamin D by hydroxylating the 24th carbon atom. This enzyme can use both 25OHD3 and 1.25 (OH) 2D3 as substrates, but has a higher affinity for 1.25 (OH) 2D3. As a result of a series of enzymatic reactions, calcitroic acid is formed, which becomes biologically inactive. On the other hand, it has been suggested that the 1,25 (OH) 2D3-23,26-lactone, which is formed in the 23-hydroxylase pathway, lowers serum calcium level, inhibits bone resorption induced by 1.25 (OH) 2D3, and stimulates the formation of collagen tissue in bone tissue [33]. In addition, it has been suggested that 24,25 (OH) 2D3 is not only a degradation product, but has an important role in bone metabolism, especially in endochondral bone formation [34].
There are two vitamin D response elements (VDRE) in the promoter region of the CYP24A1 gene [35]. When active vitamin D is bound to the these one of VDRE after heterodimerization with various molecules, thus initiates the inactivation process of vitamin D. In addition, it has been shown that CYP24A1 gene expression decreases with the effect of PTH, whereas it increases with increased FGF23 concentrations [1, 32, 36, 37]. Inactivating mutations in CYP24A1 lead to an idiopathic infantile hypercalcemia clinic characterized by hypercalcemia, hypercalciuria, nephrocalcinosis, low PTH, low 24.25 (OH) 2D3 and high 1.25 (OH) 2D3 levels [37]. As a result, CYP24A1 is a critical enzyme that protects the body from excessive accumulation and possible intoxication of vitamin D.
3-epimerase activity was first demonstrated in 2001, with the detection of the 3-epi form of 1,25 (OH) 2D3 in keratinocytes [38]. In the following years, epimer forms of 25OHD3 and other vitamin D metabolites were discovered. However, the enzyme or enzymes involved in epimerization has not yet been identifiedpurified or cloned. This enzyme changes the hydroxyl group in the 3rd carbon of the A ring from the alpha orientation to the beta orientation, causing the three-dimensional structure to change and consequently alter the activity of CYP27B1 and CYP24A1 enzymes on vitamin D metabolism. These epimers can be detected by special liquid chromatography-mass spectroscopy (LC-MC) measurement methods [2]. C-3 epimer forms of 25OHD3 and 1,25 (OH) 2D3 have been shown to have lower affinity for VDR and VDBP compared to non-epimer forms [38]. The C-3 epimer form of 1,25 (OH) 2D3 has been shown to cause PTH suppression similar to the non-epimer form, but its effects on bone tissue are not clear. In addition, epimer forms have also been shown to have non-calcium effects (anti-proliferative effect, surfactant synthesis) [39]. It has been shown that the serum levels of vitamin C-3 epimer forms are found to be 60% higher in the period between the neonatal period and one year old, and decrease after one year of age and decrease to very low levels in adulthood [2, 38]. The reason why epimer forms with limited biological activity are important is that they cause interference and false high results in serum 25OHD3 and 25OHD2 measurement. Therefore, it is important to prefer the method (especially LC–MS / MS) that can exclude this effect of epimer forms that cause serum vitamin D measurement interference. However, the use of LC–MS/MS method in the measurement of vitamin D has not become widespread in the world, and the use of this method is only recommended in selected cases.
The largest part of the circulating vitamin D is in the form of 25OHD3, and its serum concentration is in equilibrium with the level of vitamin D stored in muscle and adipose tissues. The parameter that gives the best information about the whole vitamin D pool in the body is 25OHD3 and its known half-life of 15–20 days. Most of all forms of vitamin D in circulation (85–88%) are transported by binding to VDBP and the remaining part (12–15%) to albumin [2, 40]. The serum concentration of VDBP is 4–8 nM and only 2% of it is bound with vitamin D metabolites [2]. Moreover, the affinity of VDBP to 25OHD3 is 20 times higher than 1.25 (OH) 2D3 [3]. 0.03% of 25OHD3 and 0.4% of 1.25 (OH) 2D3 are in free form [2]. In chronic liver disease or nephrotic syndrome, VDBP and albumin levels and thus total serum 25OHD3 and 1.25 (OH) 2D3 levels decrease, but the levels of free forms are not affected [41]. Likewise, since the VDBP level may decrease during the acute disease period, evaluating the body’s vitamin D pool by measuring the serum 25OHD3 level with standard immunoassays may lead to misinterpretations [42]. In conclusion, while the total levels of vitamin D forms are affected by the VDBP level, there is no relationship between VDBP and free vitamin D forms, which are essential for biological activity. It was shown that both 25OHD3 and 1.25 (OH) 2D3 levels in VDBP-null mice were lower than wild type mice, but serum PTH and calcium levels were similarly normal in both groups [43]. This supports the view that serum vitamin D level measured by the standard method may not be an indicator of biologically active vitamin D pool. In addition, the predisposition of VDBP-null mice to the development of osteomalacia after a vitamin D-restricted diet suggests that VDBP may play a role in maintaining the existing vitamin D pool [44]. In addition, some single nucleotide polymorphisms (GC1F, GC1S, GC2) in the
Vitamin D provides its biological effect in two different ways. The first is by directly affecting gene transcription (genomic effect) as other steroid hormones. This effect is relatively slow and usually occurs within hours or days. The second is the non-genomic pathway whose biological effect is relatively faster (within minutes). Vitamin D exerts its non-genomic effect by directly altering the trans-membrane passage of some ions (Ca, Cl) or by affecting intracellular signaling pathway activities (cAMP, PKA, PLC, PI-3 kinase and MAP kinase) [1, 2]. Genetic studies on vitamin D support that active vitamin D directly or indirectly regulates 0.8–5% of the total genome, suggesting the role of active vitamin D in many actions such as regulation of cellular growth, DNA repair, differentiation, apoptosis, membrane transport, cellular metabolism, adhesion and oxidative stress [1, 2, 3, 47].
The active form of vitamin D displays this effect through the vitamin D receptor (VDR). VDR is a member of the nuclear hormone receptor superfamily, which includes steroid, thyroid hormone, and retinoic acid receptors [48]. The VDR gene located on chromosome 12 consists of 427 amino acids encoded by. The structure of the VDR consists of a relatively short N-terminal domain compared to other nuclear receptors, two zinc-fingers that allow the receptor to bind to DNA, and a highly variable C-terminal region, and the hinge region connecting binding these domains (Figure 3) [2]. The DNA-binding region of the receptor is rich in cysteine, and the sequence of this region is largely conserved between species. The zinc-finger structure close to the C-terminal part of VDR determines the specificity for the VDRE (vitamin D response element), which is the binding site on the DNA. The other zinc-finger structure is involved in the heterodimerization of VDR with RXR (retinoid X receptor) [1, 2]. The ligand-binding part of the receptor consists of 12 α-helix structures (H1-12; the H12 part is also called AF2) and 3 β-sheet structures (S1-3) [49]. The AF-2 region located at the end of the C-terminal is the binding site of co-activator complex structures such as SRC (steroid receptor coactivator) and DRIP (vitamin D receptor interacting protein). Transcription is initiated by binding co-activators to this region [50]. Apart from these functional domains, there are NLS (nuclear localization signal) regions within the DNA binding region of VDR, which are necessary for maintaining transcriptional activity [2]. In addition, there is a hinge region between the ligand-binding and DNA-binding domains of the VDR that ensures molecule stabilization.
The structure of the Vitamin D receptor (VDR).
After active vitamin D crosses the target cell membrane, it interacts with the ligand-binding domain of its own receptor (VDR) in the cytoplasm of the cell. Vitamin D is embedded in the ligand-binding domain, and subsequently, in the H12 alpha-helix H12 (AF-2) region, which is located at the end of the ligand binding part [51]. This critical conformational change of AF-2 facilitates the binding of co-activators in later stages [52]. In the next step, vitamin D-bound VDR binds to RXRα to form a VDR/RXR heterodimer structure that binds to cognate VDR elements (VDRE) in the promoter region in the target genes with a high affinity to initiate gene activation or inhibition. There are many gene-specific VDREs associated with bone metabolism, xenobiotic detoxification, drug resistance, cell growth and differentiation, angiogenesis, mammalian hair growth cycle, lipid synthesis regulation, apoptosis, and immune functions, suggesting that vitamin D has numerous regulatory roles in various organs or tissues in the body [53].
After active vitamin D-VDR-RXR-VDRE interaction, the progression of transcription is controlled by co-activator and co-repressors. The best known co-activators are the p160 co-activator family (eg CBP/p300 and p/CAF) and SRC 1,2,3. Both bind to the AF-2 part and have histone acetyl transferase (HAT) activity, which enables the opening of the histone structure and thus facilitates gene expression [54]. The SRC complex has three NR regions that facilitate binding and contain LxxLL (L, leucine; x, any amino acid) motifs. Likewise, the DRIP complex (Mediator) also has NR regions with LxxLL motifs consisting of 15 or more amino acids [55]. Unlike SRC, DRIP complex does not have HAT activity. This suggests the fact that both protein complexes play a complementary role in the initiation of transcription. The mediator multi-protein complex DRIP205/MED1 (also known as MED1) accumulates around RNA polymerase 2of the initiation complex. This complex then interacts with the TATA region in the promoter region and enables transcription to be initiated [56]. Co-repressors (eg SMRT and NCoR) have histone de-acetylase activity and inhibit transcription by preventing unfolding of the histone core.
Some of the hormones that act on the nuclear hormone receptor can also exert their biological effects on the membrane receptor without the need for additional gene regulation [2]. The non-genomic effect occurs through messenger-mediated pathways. Estrogen, progesterone, testosterone, corticosteroids and thyroid hormones have been reported to exert their effects by using both genomic and non-genomic pathways [2]. Vitamin D has been shown to directly regulate the activation or distribution of various ion-transport channel proteins (for calcium and chloride) and of enzymes (protein kinase C and phospholipase C) through the membrane receptor in osteoblast, liver, muscle, and intestinal cells (Figure 4) [57, 58, 59, 60, 61, 62]. In order to demonstrate the non-genomic effect of vitamin D, many studies have been conducted on intestinal calcium absorption. Rapid vesicular calcium absorption (also called transcaltachia) has been shown in the chick intestinal tract [63]. Further experimental studies have shown that intestinal calcium transport cannot be blocked by the administration of actinomycin D (which inhibits the genomic effect) [64], whereas calcium absorption can be blocked by inhibition of voltage-gated L-type calcium channel proteins [65] or by protein kinase C [66].
Representation of the signal transduction pathways where Vitamin D has its non-genomic effect (2). After vitamin D binds to the membrane receptor, GDP in the G protein α-subunit turns into GTP and activation occurs. The α-subunit of the G protein is separated from other subunits and binds to phospholipase C (PLC). The PLC is then activated to convert phosphoinositol bisphosphate (PIP2) to inositol triphosphate (IP3) and diacylglycerol (DAG). Calcium release from the endoplasmic reticulum via the IP3 receptor (IP3R); DAG activates PKC. PKC, on the other hand, provides calcium entry into the cell via the L-type calcium channel in the membrane.
Apart from the intestinal system, it has been suggested that the non-genomic effect also occurs in chondrocytes in the growth plate and keratinocytes in the skin [67, 68]. Vitamin D is believed to exert its non-genomic effects through VDR analog and MARRS (also known as ERp57/GRp58/ERp60) receptors located on the cell membrane [69, 70]. These membrane receptors are located within the caveolar lipid layer [71]. In addition, research findings indicate that VDR is also necessary for the expression of membrane receptors that involve in the emergence of non-genomic effect [1, 2]. In studies evaluating the effects of vitamin D analogs (6-s-cis or 6-s-trans conformations), the 6-s-cis form can activate intestinal rapid calcium entry even though the VDR affinity is very low, whereas the 6-s-trans form has been shown to be ineffective in calcium metabolism [67].
One of the most important functions of vitamin D is to increase calcium absorption from the intestines. Calcium absorption from the intestinal tract occurs trans-cellular and para-cellular processes mediated through genomic and non-genomic effects. Among these, the trans-cellular pathway largely utilized by the intestinal system, which is regulated by vitamin D [2]. The absorption effect of vitamin D with non-genomic effect of calcium occurs directly on the membrane (transcaltachia). The channel-mediated calcium absorption effect of vitamin D occurs more slowly [2].
Calcium enters the epithelian cell by the effect of an electrical and chemical gradient via calcium channel protein TRPV6 (which has significant sequence homology to TRPV5 in the kidney), the transmembrane protein at the lumenal brush border edge of the intestinal epithelial cell. The expression of TRPV6 is activated by vitamin D [72]. Reduced intestinal calcium transport is observed in TRPV6 null mice [73]. Calcium entering the cell binds to calmodulin (CaM), which is bound with myosin 1A (also known as brush border myosin I). This formed complex allows calcium to be transported across the microvilli. Subsequently, the transport of calcium up to the basolateral membrane occurs inside the vesicle via calbindin-D9k (CaBP). The affinity of calcium for calbindinin is greater than for calmodulin, and better facilitates calcium transport inside the cell [74]. The calcium reaching the basolateral membrane is pumped out of the cell to systemic circulation via the Ca-ATPase (PMCA1b) pump located on the membrane [1, 2]. In addition, although it is less important, NCX (sodium/calcium exchanger), located in the basolateral region, also plays a role in excretion of calcium [2, 75]. Vitamin D shows its increasing effect on intestinal calcium absorption by inducing expression of TRPV6, CaBP and PMCAb and increasing the binding affinity of CaM to myosin 1A [1, 2].
Intestinal calcium absorption, serum calcium level and bone mineral content in Kalbindin D9k null mice (regardless of dietary calcium level) have been shown to be similar to normal mice [76]. Intestinal calcium absorption was found to be normal in calbindin D9k and TRPV6 null mice when a diet containing the daily requirement for calcium was given [77]. These findings indicate there is a mechanism other than the genomic effect through which vitamin D exerts its action (a non-genomic effect) in calcium absorption in the intestines when the amount of calcium in the diet is sufficient.
While trans-cellular calcium absorption is effective in compensating for a low-calcium diet, para-cellular calcium transport becomes important with the increase in calcium content in the diet [1]. Paracellular transport occurs through the extracellular space between the layer of the epithelial cells in the intestine. Although it was previously thought that vitamin D does not affect para-cellular calcium absorption, studies conducted in recent years indicate otherwise, with vitamin D still affecting calcium absorption by increasing levels of various transmembrane and adhesion proteins that control the extracellular space between cells [78, 79]. However, it is not clear at what stage of the paracellular pathway these proteins are involved.
Phosphate, another important molecule for bone mineralization, is actively absorbed mostly in the jejunum, with absorption influenced by vitamin D [2]. This absorption is provided by sodium-phosphate co-transporter IIb (NaPi IIb). In experimental studies, it has been shown that phosphate absorption is blocked when cycloheximide, which inhibits protein synthesis, is given [80]. This situation supports that phosphate absorption occurs by genomic effect. Vitamin D increases NaPi-IIb expression and thus phosphate absorption [2].
Most of the calcium that reaches the kidney tubules is absorbed from the proximal and distal tubules and approximately 1–2% of it is excreted through urine. Approximately 65% of calcium absorption in the kidney is passively absorbed para-cellularly from the proximal tubules with the sodium gradient and independent of vitamin D direct action [1]. The rest of the calcium is absorbed from the ascending limb of the loop of Henle (20%), the distal tubules (15–20%), and the collecting ducts (5%) [81]. Vitamin D plays an important role in calcium absorption in the distal tubules and provides active calcium absorption via the trans-cellular pathway with the help of an electrochemical gradient [1]. Calcium is taken into the cell by TRPV5 channel on the surface of the tubular cell and is transported inside the cell by calbindin-D9k and D28k. Transported to the basolateral part of the cell, calcium is released into the systemic circulation by NCX1 (sodium/calcium exchanger) and PMCA1b. This mechanism is similar to that in the intestinal tract. Vitamin D increases the expression of TRPV5, calbindin, NCX and PMCA1b.
Phosphate is reabsorbed by sodium-dependent phosphate carrier proteins (NaPi-IIa and NaPi-IIc) in proximal tubular cells under vitamin D control. In addition, for phosphate reabsorption, a Na/K-ATPase channel located in the basolateral membrane is also needed [1, 2]. The impact of vitamin D on transport channels is not clearly known. While PTH increases the lysosomal degradation of phosphate transport channels, FGF23 causes a decrease in the expression of these channels [1, 2, 82].
Calcium, phosphorus and vitamin D are important molecules for bone metabolism and health. Calcium is one of the most abundant minerals in the body and is obtained entirely from dietary sources. In addition to its various biological effects in the body, it is also essential for bone metabolism [83]. More than 99% of the total body calcium is found in the bone tissue as a calcium-phosphate mineral complex, while the remaining <1% is distributed between the intracellular and extracellular compartments [83]. While 40% of calcium outside bone tissue is bound to protein, 9% forms ionic complexes, and the remaining 51% is found as free ions [84, 85]. Ionized calcium balances the calcium pool in the intracellular-extracellular area and plays an important role in bone metabolism. This balance is provided by the cooperation of various hormones (PTH, vitamin D) and the organs they affect (kidney, bone and intestinal system) [83, 84, 85]. Where there is vitamin D deficiency (nutritional or genetic) or VDR-inactivating mutations, serum levels of calcium and phosphate, which play an important role in bone development and growth, are reduced and thus rickets/osteomalacia emerge. Rickets is a disease characterized by excessive osteoid tissue accumulation and defective mineralization of the epiphyseal plate, which occurs as a result of insufficient mineralization in the epiphyseal plates of growing bones [1, 2]. Osteomalacia is a disease characterized by a deterioration in the mineralization of the newly formed osteoid and a decrease in bone turnover.
There is a continuous remodeling cycle consisting bone tissue resorption and mineralization. When calcium, phosphorus, and vitamin D are sufficient, this cycle continues in a balanced manner. In the case of negative calcium balance caused by insufficient calcium intake with diet or increased renal calcium loss, vitamin D increases bone resorption in osteoblasts through VDR signaling, resulting in calcium passage from bone to blood, which leads to impaired bone mineralization. Vitamin D increases the expression of RANKL (receptor activator of NF-κB ligand), which is an osteoclastogenic factor from osteoblasts [86, 89]. RANKL stimulates osteoclastogenesis and increases osteoclast formation by binding to its related receptor, RANK [87]. In conclusion, in the case of negative calcium balance, vitamin D tries to keep the serum calcium level in a certain balance by increasing resorption and decreasing mineralization [1].
In the case of a positive calcium balance, the osteoblastogenic activity of vitamin D is prominent. In this situation where anti-resorbtive effect is in the predominant, bone mineral density increases. The occurrence of this effect has been associated with a decrease in the RANKL/OPG (osteoproteogerin) ratio and an increase in LRP-5 (LDL receptor related protein 5) expression [1]. LRP-5 is controlled by the VDR and is a necessary co-receptor for the anabolic effect of osteoblasts [88]. In addition, vitamin D plays a role in the proliferation of chondrocytes in the growth plate through genomic action.
Pro-vitamin-D3, pre-vitamin D3 and then vitamin D3 (cholecalciferol) conversion in the skin is under the control of UV radiation. Serum vitamin D concentration reaches its highest level 24–48 hours after exposure to UV radiation and then shows a gradual decrease. The half-life of serum vitamin D is 36–72 hours. Vitamin D, which is a fat-soluble vitamin, is stored in adipose tissue for later use. The ability of vitamin D to be stored in adipose tissue extends its total half-life in the body up to approximately 2 months.
There is little information on how this enzyme is regulated because of the few studies performed. What is known is that serum vitamin D level is inversely related to the rate of 25-hydroxylation in the liver, and the synthesis of 25OHD3 from vitamin D (cholecalciferol) is regulated by the 25-hydroxylase enzyme
Serum active vitamin D levels in healthy adults vary within extremely narrow ranges, so that even in cases of vitamin D intoxication, serum levels may remain normal. 1-alpha hydroxylation activity in the kidney is controlled by PTH, calcium and phosphorus. Hypocalcemia, increased PTH, and hypophosphatemia will stimulate increases in active vitamin D production through renal 1-alpha hydroxylase enzyme activation, while hypercalcemia, FGF-23 secreted from osteoblasts, and active vitamin D itself have an inhibitory effect on active vitamin D synthesis through the renal 1-alpha hydroxylase enzyme. Active vitamin D increases FGF23 synthesis from osteoblasts. FGF23 suppresses the 1-alpha hydroxylase enzyme and increases the activity of 24 hydroxylase enzymes. In addition, hypercalcemia suppressing PTH and hyperphosphatemia by increasing FGF23 levels results in 1-alpha hydroxylase enzyme activity inhbition [1, 2, 3]. It is also suggested that calcium and phosphate have a direct regulatory effect on 1-alpha hydroxylase enzyme [89].
Calcitonin is known to reduce serum calcium levels through osteoclast inhibition. In addition, this hormone has been shown to increase the expression of CYP27B1, the gene encoding the 1-alpha hydroxylase enzyme, in normocalcemic pregnant women due to the increase in calcium need. In this way, active vitamin D synthesis and consequently intestinal calcium absorption is increased [1, 90]. Apart from calcitonin, it has been suggested that prolactin also increases CYP27B1 expression, especially during lactation, and thus contributes to the increased calcium demand of the body [1, 91].
CYP3A4 enzyme in the liver and intestinal system has also been shown to be effective in the inactivation of 25OHD3 and reduction of active vitamin D [92]. Long-term use of drugs such as phenytoin, rifampicin, and carbamazepine may lead to up-regulation of the CYP3A4 enzyme and thus to a decrease in serum 25OHD3 and active vitamin D levels.
When serum calcium, phosphate and PTH levels are within normal levels, 25OHD3 and 1–25 (OH) 2 D3 are metabolized into biologically inactive forms by activation of 24-alpha hydroxylase enzyme in the kidneys (24–25 dihydroxy vitamin D3 and 1,24, 25 trihydroxy vitamin D3). This enzyme preferably binds to 1–25 (OH) 2 D3, thus limiting the effect of active vitamin D in tissues through inactivation [2]. The low level of 24-hydroxylase enzyme activity leads to high levels of 1–25 (OH) 2D3 and thus hypercalcemia. In addition, it has been suggested that a decrease in this enzyme activity may lead to impairment in intra-membranous bone mineralization [1, 2]. On the other hand, when 1–25 (OH) 2 D3 synthesis decreases, 1-alpha hydroxylase enzyme activity increases and 24-hydroxylase enzyme activity decreases. It is also known that FGF23 increases the activity of 24 hydroxylase enzymes [1, 2].
Numerous studies have shown active vitamin D synthesis by 1-alpha hydroxylase enzyme is not only a renal feature [2, 93]. The gene encoding the 1-alpha hydroxylase enzyme and the vitamin D receptor gene can be expressed in many cells or tissues such as skin, placenta, prostate, parathyroid, bone tissue, colon, lung, breast tissue, monocytes and macrophages, as well as renal cells. It has been reported that active vitamin D synthesized in the aforementioned tissues functions mostly as an intracrine or paracrine factor in the tissues where they are located, and does not contribute to the active vitamin D levels in the circulation, except for some special cases [1, 2]. Since PTH and FGF-23 receptors are not found in these tissues, they are not directly involved in controlling active vitamin D synthesis. However, it is propable that PTH increases the effect of vitamin D through posttranscriptional modification [31]. Unlike in other tissues, in activated macrophages, there is also no negative feedback of active vitamin D on 1-alpha hydroxylase enzyme [91]. Moreover, although the 24-hydroxylase enzyme is expressed in these cells, its function is not fully understood. Cytokines such as IL-1, TNF-α, IFN-γ induce the synthesis of active vitamin D in keratinocytes. Unlike macrophages, keratinocytes have a fully functional 24-hydroxylase enzyme activity and is induced by active vitamin D. In this way, active vitamin D limits its own synthesis in the epidermis through alternative catabolism [1, 2, 93].
Measurement of serum levels of vitamin D, which plays an important role in calcium and phosphorus metabolism and bone mineralization, is routinely performed worldwide. For this, it is preferred to measure the 25OHD level, which has a longer half-life (24–36 hours), can be taken exogenously, and can be synthesized endogenously. The half-life of the 1–25 (OH) 2D3 form is short (4–6 hours), and its serum levels are 1000 times lower than 25OHD. For these reasons, the active form is not preferred for routine measurement. In this section, the measurement methods of 25OHD vitamin are discussed.
To date, many methods have been developed for measuring serum vitamin D levels. These methods are basically divided into two groups. One methodology is the use of competitive binding and immunoassays: radioimmunoassay (RIA), enzyme immunoassay (EIA/ELISA), chemiluminescent immunoassay (CLIA), electrochemiluminescence assay (ECLIA), and competitive protein binding assay. The other methodology involves chemical methods. Chemical methods are based on the non-immunological direct detection methods typically after preparative chromatographic separation. Chemical methods include high performance liquid chromatography (HPLC) and LC/MS (liquid chromatography-mass spectrometer).
The first method used in the measurement of vitamin D is the competitive binding method in which VDBP binds. This method was first reported in 1971 and identifies 25OHD2 and 25OHD3 forms equally [94]. Limitations of this method include the incubation period of 10 days and its inability to separate some polar vitamin D metabolites [24,25(OH)2D, 25,26 (OH)2D ve 25,26 (OH)2D-26,23--lactone] [94]. In the late 1970s, the HPLC method was developed that can exclude the effect of polar vitamin D metabolites causing interference to the chromatographic method [95]. The advantages of this method, which uses a UV absorption technique, include the absence of lipid and polar vitamin D metabolite interference, the ability to measure 25OHD2 and 25OHD3 separated at high resolution, and a high specificity and reliability. Its disadvantages include the use of excess sample amounts, equipment cost, a need for preparative chromatography, and interference by other UV-absorbing compounds, and that the method is somewhat complex and not easily practical. It would not be considered a routine diagnostic test, as it is used in only about 2% of laboratories in the world) [94, 95]. With the later development of the RIA method, the value of quantifying vitamin levels improved. The advantages of this method type are that sample amount can be small and not pre-analytical preparative purification process is required. The assay is economical and easily applicable, and results reliable. As to the disadvantages, chemical and radioactive (with the RIA) waste are issues, and there is cross-reactivity with polar vitamin D metabolites as in the earlier competitive binding type assays. The RIA also is 100% specific for 25OHD3 and 75% specific for 25OHD2, so the final calculation requires an adjustment [94, 96]. Nonetheless automated immunoassay methods are widely used in our country and all over the world (approximately 76% of laboratories in the world) [97]. Requiring less sample volume, not requiring sample preparation, easy equipment supply, easy application, fast results, no cross-reactivity with C3-epimer forms, and low user error are among the reasons why this method is used more widely in the world [97, 98]. Despite its widespread use, this method has some significant disadvantages. In this method, 25OHD2 and 25OHD3 cannot be distinguished and both are measured as total of 25OHD. This may lead to misinterpretation in countries that use ergocalciferol in treatment (eg America) [97]. In addition, automated immunoassay results can be affected by pregnancy, whether sampled from intensive care patients, the presence of chronic disease and liver diseases, all of which affect the amount of VDBP synthesized from the liver [99, 100]. In addition, it has been reported that there is a high probability of interferences involving automated immunoassay measurement methods [97, 101].
Due to the low reliability of immunoassay measurements, this method has begun to be replaced by LC–MS/MS, which is considered to be the “gold standard” method. This method is used in approximately 18% of laboratories around the world, and it is estimated that its prevalence will increase due to its more accurate and precise results [97]. This method provides distinguishing quantitative measurements of both 25OHD2 and 25OHD3 forms in both serum and plasma [102]. Hence, 25OHD2 can be easily monitored in countries where ergocalciferol is widely used. In addition, with this method, C-3 epimer forms of vitamin D, which are present in high levels in serum in the first year, can be separated from other forms, and these metabolites are prevented from causing vitamin D measurement interference [97, 102].
In recent years, instead of measuring the level of vitamin D bound to VDBP, there is a strong belief in the need to measure free vitamin D levels as that is the form that accounts for the principal bioactivity. Routine methods measure the level of 25OHD vitamin bound to VDBP and provide information about the total body pool. In parallel with this, if the total body pool is sufficient, free vitamin D level is estimated to be sufficient. However, the situation is somewhat complex in obese patients, where a negative correlation between the amount of adipose tissue and serum vitamin D levels has been reported. In these cases, it has been reported that serum 25OHD level is lower than those with normal body weight, since large adipose tissue creates a larger pool for vitamin D sequestration [101, 102, 103, 104, 105]. In other words, serum 25OHD level in obese patients may not provide information about the body pool of vitamin D. It is thought that it would be more valuable to measure vitamin D levels that are not bound to binding protein in these cases. However, there is a serious standardization problem in the measurement of free 25OHD [103]. Also, Bikle et al. [106] proposed a method by which free 25OHD vitamin can be calculated. However, studies have shown that the results obtained with this method are not reliable [107]. Finally, direct measurement or indirect calculations of free forms of vitamin D are not yet suitable for routine use.
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All published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Therefore, it is necessary to evaluate the effectiveness of determining the age of deposition using zircon age data. We carried out U–Pb dating of detrital zircons from sandstone at eight sites in the Cretaceous Shimanto accretionary complex on Kii Peninsula, Japan, with the aim of evaluating the accuracy of U–Pb zircon ages as indicators of the depositional age of sedimentary rocks by comparing zircon ages with radiolarian ages. Our results reveal zircons of late Cretaceous age, and the youngest peak ages are in good agreement with depositional ages inferred from radiolarian fossils. In addition, the youngest peak ages become younger as tectono-structurally downwards, and this tendency is clearer for the zircon ages than for the radiolarian ages. These results indicate that newly crystalized zircons were continuously supplied to the sediment by constant igneous activity during the late Cretaceous and that zircon ages provide remarkably useful information for determining the age of deposition in the Cretaceous Shimanto accretionary complex.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Tetsuya Tokiwa, Makoto Takeuchi, Yusuke Shimura, Kazuho Shobu,\nAkari Ota, Koshi Yamamoto and Hiroshi Mori",authors:[{id:"150531",title:"Dr.",name:"Koshi",middleName:null,surname:"Yamamoto",slug:"koshi-yamamoto",fullName:"Koshi Yamamoto"},{id:"194144",title:"Dr.",name:"Tetsuya",middleName:null,surname:"Tokiwa",slug:"tetsuya-tokiwa",fullName:"Tetsuya Tokiwa"},{id:"204259",title:"Dr.",name:"Makoto",middleName:null,surname:"Takeuchi",slug:"makoto-takeuchi",fullName:"Makoto Takeuchi"},{id:"204260",title:"Mr.",name:"Yusuke",middleName:null,surname:"Shimura",slug:"yusuke-shimura",fullName:"Yusuke Shimura"},{id:"204261",title:"Mr.",name:"Kazuho",middleName:null,surname:"Shobu",slug:"kazuho-shobu",fullName:"Kazuho Shobu"},{id:"204262",title:"Ms.",name:"Akari",middleName:null,surname:"Ota",slug:"akari-ota",fullName:"Akari Ota"},{id:"204263",title:"Dr.",name:"Hiroshi",middleName:null,surname:"Mori",slug:"hiroshi-mori",fullName:"Hiroshi Mori"}]},{id:"55296",doi:"10.5772/68112",title:"Alteration Reaction and Mass Transfer via Fluids with Progress of Fracturing along the Median Tectonic Line, Mie Prefecture, Southwest Japan",slug:"alteration-reaction-and-mass-transfer-via-fluids-with-progress-of-fracturing-along-the-median-tecton",totalDownloads:1218,totalCrossrefCites:1,totalDimensionsCites:8,abstract:"We have analyzed mass transfer in the cataclasite samples collected from the Median Tectonic Line, southwest Japan, in which the degree of fracturing is well correlated with the bulk rock chemical compositions determined by the X-ray fluorescence (XRF) analysis. The results of “isocon” analysis indicate not only a large volume increase up to 110% but also the two-stage mass transfer during cataclasis. At the first stage from the very weakly to weakly fractured rocks, the weight percents of SiO2, Na2O, and K2O increase, while those of TiO2, FeO, MnO, MgO, and CaO decrease. At the second stage from the weakly to moderately and strongly fractured rocks, the trend of mass transfer is reversed. The principal component analysis reveals that the variation of chemical compositions in the cataclasite samples can be mostly interpreted by the mass transfer via fluids and by the difference in chemical composition in the protolith rocks to lesser degree. Finally, the changes in the modal composition of minerals with increasing cataclasis analyzed by the X-ray diffraction (XRD) with the aid of “RockJock” software clearly elucidate that the mass transfer of chemical elements was caused by dissolution and precipitation of minerals via fluids in the cataclasite samples.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Yumi Kaneko, Toru Takeshita, Yuto Watanabe, Norio Shigematsu\nand Ko‐Ichiro Fujimoto",authors:[{id:"194157",title:"M.Sc.",name:"Yumi",middleName:null,surname:"Kaneko",slug:"yumi-kaneko",fullName:"Yumi Kaneko"},{id:"204607",title:"Prof.",name:"Toru",middleName:null,surname:"Takeshita",slug:"toru-takeshita",fullName:"Toru Takeshita"},{id:"204608",title:"MSc.",name:"Yuto",middleName:null,surname:"Watanabe",slug:"yuto-watanabe",fullName:"Yuto Watanabe"},{id:"204609",title:"Dr.",name:"Norio",middleName:null,surname:"Shigematsu",slug:"norio-shigematsu",fullName:"Norio Shigematsu"},{id:"204610",title:"Dr.",name:"Ko-Ichiro",middleName:null,surname:"Fujimoto",slug:"ko-ichiro-fujimoto",fullName:"Ko-Ichiro Fujimoto"}]},{id:"54870",doi:"10.5772/67559",title:"Deposition and Deformation of Modern Accretionary-Type Forearc Basins: Linking Basin Formation and Accretionary Wedge Growth",slug:"deposition-and-deformation-of-modern-accretionary-type-forearc-basins-linking-basin-formation-and-ac",totalDownloads:1773,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Since a comprehensive review of forearc basins was published by Dickinson more than 20 years ago, a significant amount of new data about them have been published. These recent studies revealed details of depositional and deformation styles in the forearc basins, suggesting the formation processes were not unique. In this chapter, we reviewed modern forearc basins to understand how is the basin stratigraphy related with growth of accretionary wedges. The results indicate forearc basin can be classified into two (single‐ and two‐wedge models) plus one (strike‐slip model): (1) the single‐wedge model which is characterized by landward tilting of the basin strata ascribed to asymmetrical doubly vergent (single‐vergent) uplift of the outer arc high with forethrusts (seaward‐vergent thrusts in the pro‐wedge); (2) the two‐wedge model which is marked by contractional deformation caused by symmetrical doubly vergent uplift of the wedge with forethrusts in the prowedge and back‐thrusts (landward‐vergent thrusts) in the retro‐wedge; and (3) the strike‐slip model which is an additional one being represented by transpressional and/or transtensional deformations due to oblique subduction. We speculate that these models spatially and temporally depend on material fluxes at the plate interfaces that affect geometry and mechanical strength of backstops.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Atsushi Noda and Ayumu Miyakawa",authors:[{id:"161716",title:"Dr.",name:"Atsushi",middleName:null,surname:"Noda",slug:"atsushi-noda",fullName:"Atsushi Noda"},{id:"204603",title:"Dr.",name:"Ayumu",middleName:null,surname:"Miyakawa",slug:"ayumu-miyakawa",fullName:"Ayumu Miyakawa"}]},{id:"54596",doi:"10.5772/67960",title:"Paleomagnetic Studies on Miocene Sequences of Hokutan and Tottori Groups in Southwest Japan: Implications for Middle Miocene Rotational Movement of Southwest Japan Block Associated with the Japan Sea Opening",slug:"paleomagnetic-studies-on-miocene-sequences-of-hokutan-and-tottori-groups-in-southwest-japan-implicat",totalDownloads:1524,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Miocene sequences composed of volcanic rocks and overlying marine sediments distributing at the Japan Sea side of Southwest Japan have been considered to form related to the rifting and subsequent spreading of the Japan Sea back-arc basin in Miocene time. We performed paleomagnetic investigations on the sequences in the eastern San’in district, the Hokutan and Tottori Groups. Paleomagnetic analyses on samples from 33 sites indicated that characteristic magnetic components from five sites of volcanic rocks in the Hokutan Group and from four sites of marine sediments in the Tottori Group were regarded as primary components. An obtained paleomagnetic direction of the volcanic rocks has an easterly deflected declination (D = 23.9° ± 20.2°), while that of the marine sediments shows no significant deflection in declination (D = 17.8° ± 19.1°). Through the comparison with paleomagnetic data from the Miocene sequences in Southwest Japan, it is suggested that magnetic polarities of the volcanic and sedimentary sequences are assigned to C5Cn and C5Br-C5Bn, respectively, and that the eastern San’in district suffered a clockwise rotation of 24° at around 16 Ma after the early Miocene volcanic activity and before the middle Miocene marine transgression in the whole clockwise rotation process of Southwest Japan related to the Japan Sea opening.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Naoto Ishikawa, Takashi Suzuki and Shiro Ishida",authors:[{id:"194180",title:"Dr.",name:"Naoto",middleName:null,surname:"Ishikawa",slug:"naoto-ishikawa",fullName:"Naoto Ishikawa"},{id:"204504",title:"Dr.",name:"Takashi",middleName:null,surname:"Suzuki",slug:"takashi-suzuki",fullName:"Takashi Suzuki"},{id:"204505",title:"Prof.",name:"Shiro",middleName:null,surname:"Ishida",slug:"shiro-ishida",fullName:"Shiro Ishida"}]},{id:"54454",doi:"10.5772/67669",title:"Structural Features Along the Median Tectonic Line in Southwest Japan: An Example of Multiphase Deformation on an Arc‐Bisecting Fault",slug:"structural-features-along-the-median-tectonic-line-in-southwest-japan-an-example-of-multiphase-defor",totalDownloads:1280,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"A geological survey for the Late Cretaceous Izumi Group distributed on the Median Tectonic Line (MTL) active fault system in the central part of southwestern Japan has revealed varied deformation styles. Among the confined deformation zones found in the western and central parts of the study area, some are located far from the active trace of the MTL (Negoro Fault), at distances of up to 300–350 m. Such kink zones may have been generated during a contraction phase of the MTL from the end of the Pliocene to the early Pleistocene. We identified clear active foldings in a narrow zone sandwiched between a north dextral and a south reverse active fault. Western and eastern upheavals of the crustal sliver show ridge and domal active morphologies, respectively. Structural analysis was extended to the north of the MTL, where the Izumi Group has suffered multiphase deformation since the Cretaceous. The phase stripping method was introduced to extract the neotectonic trend, which successfully delineated complicated deformation zones related to the morphological divergence of the MTL active fault system.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Yasuto Itoh and Tomotaka Iwata",authors:[{id:"46893",title:"Dr.",name:"Yasuto",middleName:null,surname:"Itoh",slug:"yasuto-itoh",fullName:"Yasuto Itoh"},{id:"203882",title:"Prof.",name:"Tomotaka",middleName:null,surname:"Iwata",slug:"tomotaka-iwata",fullName:"Tomotaka Iwata"}]}],mostDownloadedChaptersLast30Days:[{id:"54840",title:"Effectiveness for Determination of Depositional Age by Detrital Zircon U–Pb Age in the Cretaceous Shimanto Accretionary Complex of Japan",slug:"effectiveness-for-determination-of-depositional-age-by-detrital-zircon-u-pb-age-in-the-cretaceous-sh",totalDownloads:1473,totalCrossrefCites:8,totalDimensionsCites:13,abstract:"Detrital zircon U–Pb ages indicate the crystallization age. Therefore, it is necessary to evaluate the effectiveness of determining the age of deposition using zircon age data. We carried out U–Pb dating of detrital zircons from sandstone at eight sites in the Cretaceous Shimanto accretionary complex on Kii Peninsula, Japan, with the aim of evaluating the accuracy of U–Pb zircon ages as indicators of the depositional age of sedimentary rocks by comparing zircon ages with radiolarian ages. Our results reveal zircons of late Cretaceous age, and the youngest peak ages are in good agreement with depositional ages inferred from radiolarian fossils. In addition, the youngest peak ages become younger as tectono-structurally downwards, and this tendency is clearer for the zircon ages than for the radiolarian ages. These results indicate that newly crystalized zircons were continuously supplied to the sediment by constant igneous activity during the late Cretaceous and that zircon ages provide remarkably useful information for determining the age of deposition in the Cretaceous Shimanto accretionary complex.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Tetsuya Tokiwa, Makoto Takeuchi, Yusuke Shimura, Kazuho Shobu,\nAkari Ota, Koshi Yamamoto and Hiroshi Mori",authors:[{id:"150531",title:"Dr.",name:"Koshi",middleName:null,surname:"Yamamoto",slug:"koshi-yamamoto",fullName:"Koshi Yamamoto"},{id:"194144",title:"Dr.",name:"Tetsuya",middleName:null,surname:"Tokiwa",slug:"tetsuya-tokiwa",fullName:"Tetsuya Tokiwa"},{id:"204259",title:"Dr.",name:"Makoto",middleName:null,surname:"Takeuchi",slug:"makoto-takeuchi",fullName:"Makoto Takeuchi"},{id:"204260",title:"Mr.",name:"Yusuke",middleName:null,surname:"Shimura",slug:"yusuke-shimura",fullName:"Yusuke Shimura"},{id:"204261",title:"Mr.",name:"Kazuho",middleName:null,surname:"Shobu",slug:"kazuho-shobu",fullName:"Kazuho Shobu"},{id:"204262",title:"Ms.",name:"Akari",middleName:null,surname:"Ota",slug:"akari-ota",fullName:"Akari Ota"},{id:"204263",title:"Dr.",name:"Hiroshi",middleName:null,surname:"Mori",slug:"hiroshi-mori",fullName:"Hiroshi Mori"}]},{id:"54341",title:"Oki-Dozen Dike Swarm: Effect of the Regional Stress Field on Volcano-Tectonic Orientations",slug:"oki-dozen-dike-swarm-effect-of-the-regional-stress-field-on-volcano-tectonic-orientations",totalDownloads:1504,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"This article presents new field, geochronological, and geochemical data for the Late Miocene Oki-dozen dike swarm (ODS), southwest Japan. This swarm is part of a volcanic suite comprising mafic and silicic dikes, sills, and pyroclastic cones from which we obtained structural measurements at a various genetic orders and scales. The mafic magmas generated three dike swarms with dikes oriented to NW-SE, N-S, and NE-SW. In comparison, the silicic intrusions do not have a preferred orientation but instead appear to radiate from the center of the volcanic suite. Comparison of the maximum thickness of 37 dikes with SiO2 content (wt%) yielded a critical thickness (T\ncr\n) value of T\ncr\n = 0.2 × (SiO2 − 40). These data indicate that the orientations of dikes were controlled by the magnitude of dike tip pressure and magma overpressure, both of which positively correlate with SiO2 concentrations. The silicic units yield estimated pressures (up to 15–60 MPa) that are large enough to have counteracted the regional stress field, whereas the mafic dike swarm only yielded lower pressures. This result suggests that comparative analysis at a range of scales is essential for the accurate determination on the tectonic stress field by igneous rocks.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Daisuke Miura, Kiyoshi Toshida, Ken-ichi Arai, Takeshi Wachi and\nYutaka Wada",authors:[{id:"194873",title:"Dr.",name:"Daisuke",middleName:null,surname:"Miura",slug:"daisuke-miura",fullName:"Daisuke Miura"},{id:"203853",title:"Mr.",name:"Kiyoshi",middleName:null,surname:"Toshida",slug:"kiyoshi-toshida",fullName:"Kiyoshi Toshida"},{id:"203854",title:"Mr.",name:"Ken'Ichi",middleName:null,surname:"Arai",slug:"ken'ichi-arai",fullName:"Ken'Ichi Arai"},{id:"203856",title:"Prof.",name:"Yutaka",middleName:null,surname:"Wada",slug:"yutaka-wada",fullName:"Yutaka Wada"},{id:"204024",title:"Mr.",name:"Takeshi",middleName:null,surname:"Wachi",slug:"takeshi-wachi",fullName:"Takeshi Wachi"}]},{id:"54596",title:"Paleomagnetic Studies on Miocene Sequences of Hokutan and Tottori Groups in Southwest Japan: Implications for Middle Miocene Rotational Movement of Southwest Japan Block Associated with the Japan Sea Opening",slug:"paleomagnetic-studies-on-miocene-sequences-of-hokutan-and-tottori-groups-in-southwest-japan-implicat",totalDownloads:1524,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Miocene sequences composed of volcanic rocks and overlying marine sediments distributing at the Japan Sea side of Southwest Japan have been considered to form related to the rifting and subsequent spreading of the Japan Sea back-arc basin in Miocene time. We performed paleomagnetic investigations on the sequences in the eastern San’in district, the Hokutan and Tottori Groups. Paleomagnetic analyses on samples from 33 sites indicated that characteristic magnetic components from five sites of volcanic rocks in the Hokutan Group and from four sites of marine sediments in the Tottori Group were regarded as primary components. An obtained paleomagnetic direction of the volcanic rocks has an easterly deflected declination (D = 23.9° ± 20.2°), while that of the marine sediments shows no significant deflection in declination (D = 17.8° ± 19.1°). Through the comparison with paleomagnetic data from the Miocene sequences in Southwest Japan, it is suggested that magnetic polarities of the volcanic and sedimentary sequences are assigned to C5Cn and C5Br-C5Bn, respectively, and that the eastern San’in district suffered a clockwise rotation of 24° at around 16 Ma after the early Miocene volcanic activity and before the middle Miocene marine transgression in the whole clockwise rotation process of Southwest Japan related to the Japan Sea opening.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Naoto Ishikawa, Takashi Suzuki and Shiro Ishida",authors:[{id:"194180",title:"Dr.",name:"Naoto",middleName:null,surname:"Ishikawa",slug:"naoto-ishikawa",fullName:"Naoto Ishikawa"},{id:"204504",title:"Dr.",name:"Takashi",middleName:null,surname:"Suzuki",slug:"takashi-suzuki",fullName:"Takashi Suzuki"},{id:"204505",title:"Prof.",name:"Shiro",middleName:null,surname:"Ishida",slug:"shiro-ishida",fullName:"Shiro Ishida"}]},{id:"55296",title:"Alteration Reaction and Mass Transfer via Fluids with Progress of Fracturing along the Median Tectonic Line, Mie Prefecture, Southwest Japan",slug:"alteration-reaction-and-mass-transfer-via-fluids-with-progress-of-fracturing-along-the-median-tecton",totalDownloads:1218,totalCrossrefCites:1,totalDimensionsCites:8,abstract:"We have analyzed mass transfer in the cataclasite samples collected from the Median Tectonic Line, southwest Japan, in which the degree of fracturing is well correlated with the bulk rock chemical compositions determined by the X-ray fluorescence (XRF) analysis. The results of “isocon” analysis indicate not only a large volume increase up to 110% but also the two-stage mass transfer during cataclasis. At the first stage from the very weakly to weakly fractured rocks, the weight percents of SiO2, Na2O, and K2O increase, while those of TiO2, FeO, MnO, MgO, and CaO decrease. At the second stage from the weakly to moderately and strongly fractured rocks, the trend of mass transfer is reversed. The principal component analysis reveals that the variation of chemical compositions in the cataclasite samples can be mostly interpreted by the mass transfer via fluids and by the difference in chemical composition in the protolith rocks to lesser degree. Finally, the changes in the modal composition of minerals with increasing cataclasis analyzed by the X-ray diffraction (XRD) with the aid of “RockJock” software clearly elucidate that the mass transfer of chemical elements was caused by dissolution and precipitation of minerals via fluids in the cataclasite samples.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Yumi Kaneko, Toru Takeshita, Yuto Watanabe, Norio Shigematsu\nand Ko‐Ichiro Fujimoto",authors:[{id:"194157",title:"M.Sc.",name:"Yumi",middleName:null,surname:"Kaneko",slug:"yumi-kaneko",fullName:"Yumi Kaneko"},{id:"204607",title:"Prof.",name:"Toru",middleName:null,surname:"Takeshita",slug:"toru-takeshita",fullName:"Toru Takeshita"},{id:"204608",title:"MSc.",name:"Yuto",middleName:null,surname:"Watanabe",slug:"yuto-watanabe",fullName:"Yuto Watanabe"},{id:"204609",title:"Dr.",name:"Norio",middleName:null,surname:"Shigematsu",slug:"norio-shigematsu",fullName:"Norio Shigematsu"},{id:"204610",title:"Dr.",name:"Ko-Ichiro",middleName:null,surname:"Fujimoto",slug:"ko-ichiro-fujimoto",fullName:"Ko-Ichiro Fujimoto"}]},{id:"54454",title:"Structural Features Along the Median Tectonic Line in Southwest Japan: An Example of Multiphase Deformation on an Arc‐Bisecting Fault",slug:"structural-features-along-the-median-tectonic-line-in-southwest-japan-an-example-of-multiphase-defor",totalDownloads:1280,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"A geological survey for the Late Cretaceous Izumi Group distributed on the Median Tectonic Line (MTL) active fault system in the central part of southwestern Japan has revealed varied deformation styles. Among the confined deformation zones found in the western and central parts of the study area, some are located far from the active trace of the MTL (Negoro Fault), at distances of up to 300–350 m. Such kink zones may have been generated during a contraction phase of the MTL from the end of the Pliocene to the early Pleistocene. We identified clear active foldings in a narrow zone sandwiched between a north dextral and a south reverse active fault. Western and eastern upheavals of the crustal sliver show ridge and domal active morphologies, respectively. Structural analysis was extended to the north of the MTL, where the Izumi Group has suffered multiphase deformation since the Cretaceous. The phase stripping method was introduced to extract the neotectonic trend, which successfully delineated complicated deformation zones related to the morphological divergence of the MTL active fault system.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Yasuto Itoh and Tomotaka Iwata",authors:[{id:"46893",title:"Dr.",name:"Yasuto",middleName:null,surname:"Itoh",slug:"yasuto-itoh",fullName:"Yasuto Itoh"},{id:"203882",title:"Prof.",name:"Tomotaka",middleName:null,surname:"Iwata",slug:"tomotaka-iwata",fullName:"Tomotaka Iwata"}]}],onlineFirstChaptersFilter:{topicId:"657",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"1",title:"Oral Health",coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",isOpenForSubmission:!0,editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",slug:"sandra-marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",biography:"Dr. Sandra A. Marinho is an Associate Professor and Brazilian researcher at the State University of Paraíba (Universidade Estadual da Paraíba- UEPB), Campus VIII, located in Araruna, state of Paraíba since 2011. She holds a degree in Dentistry from the Federal University of Alfenas (UNIFAL), while her specialization and professional improvement in Stomatology took place at Hospital Heliopolis (São Paulo, SP). Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). Dr. Marinho's experience in Dentistry mainly covers the following subjects: oral diagnosis, oral radiology; oral medicine; lesions and oral infections; oral pathology, laser therapy and epidemiological studies.",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"2",title:"Prosthodontics and Implant Dentistry",coverUrl:"https://cdn.intechopen.com/series_topics/covers/2.jpg",isOpenForSubmission:!0,editor:{id:"179568",title:"Associate Prof.",name:"Wen Lin",middleName:null,surname:"Chai",slug:"wen-lin-chai",fullName:"Wen Lin Chai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHGAQA4/Profile_Picture_2022-05-23T14:31:12.png",biography:"Professor Dr. Chai Wen Lin is currently a lecturer at the Department of Restorative Dentistry, Faculty of Dentistry of the University of Malaya. She obtained a Master of Dental Science in 2006 and a Ph.D. in 2011. Her Ph.D. research work on the soft tissue-implant interface at the University of Sheffield has yielded several important publications in the key implant journals. She was awarded an Excellent Exchange Award by the University of Sheffield which gave her the opportunity to work at the famous Faculty of Dentistry of the University of Gothenburg, Sweden, under the tutelage of Prof. Peter Thomsen. In 2016, she was appointed as a visiting scholar at UCLA, USA, with attachment in Hospital Dentistry, and involvement in research work related to zirconia implant. In 2016, her contribution to dentistry was recognized by the Royal College of Surgeon of Edinburgh with her being awarded a Fellowship in Dental Surgery. She has authored numerous papers published both in local and international journals. She was the Editor of the Malaysian Dental Journal for several years. Her main research interests are implant-soft tissue interface, zirconia implant, photofunctionalization, 3D-oral mucosal model and pulpal regeneration.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorTwo:{id:"479686",title:"Dr.",name:"Ghee Seong",middleName:null,surname:"Lim",slug:"ghee-seong-lim",fullName:"Ghee Seong Lim",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003ScjLZQAZ/Profile_Picture_2022-06-08T14:17:06.png",biography:"Assoc. Prof Dr. Lim Ghee Seong graduated with a Bachelor of Dental Surgery from University of Malaya, Kuala Lumpur in 2008. He then pursued his Master in Clinical Dentistry, specializing in Restorative Dentistry at Newcastle University, Newcastle, UK, where he graduated with distinction. He has also been awarded the International Training Fellowship (Restorative Dentistry) from the Royal College of Surgeons. His passion for teaching then led him to join the faculty of dentistry at University Malaya and he has since became a valuable lecturer and clinical specialist in the Department of Restorative Dentistry. He is currently the removable prosthodontic undergraduate year 3 coordinator, head of the undergraduate module on occlusion and a member of the multidisciplinary team for the TMD clinic. He has previous membership in the British Society for Restorative Dentistry, the Malaysian Association of Aesthetic Dentistry and he is currently a lifetime member of the Malaysian Association for Prosthodontics. Currently, he is also the examiner for the Restorative Specialty Membership Examinations, Royal College of Surgeons, England. He has authored and co-authored handful of both local and international journal articles. 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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. 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He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"22",type:"subseries",title:"Applied Intelligence",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence",scope:"This field is the key in the current industrial revolution (Industry 4.0), where the new models and developments are based on the knowledge generation on applied intelligence. 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His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. 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He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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