Bridge specifications.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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It is highly demanded to establish sufficient management systems for the inspection of existing concrete infrastructures in order to manage and extend their service lives. As for aging infrastructure, severe deterioration is currently reported, where it is known as a critical issue in our society, and large budgets are required to repair damaged structures. Since budgetary restrictions are often imposed, preventive and proactive maintenance techniques of infrastructure are sufficiently needed with nondestructive testing (NDT) methods. In addition to conventional NDT, innovative methods must be established to appropriately assess and evaluate damage and repair and retrofit recovery in concrete structures. Inspection techniques after crack repair methods application for existing structures to assess repair installations have not yet been practically developed, meanwhile improper repair efforts have resulted in re-deterioration. Refilling internal cracks with repair materials from the concrete surface, epoxy injection, and patch repair methods are widely implemented. In most cases, re-deterioration could be led by the unknown and remained internal defects. Consequently, it is very important to implement and establish inspection techniques which can visualize internal defects as a countermeasure with repair works.
\nFor such infrastructure as bridges and tunnels, it is generally recognized that appropriate maintenance works are necessary. Prior to extensive damage and failure in existing structures, essential issues include establishing a maintenance system for reinforced concrete (RC) members with the sufficient measures. Epoxy injection and patch repair methods have been widely and practically introduced to repair and re-strengthen RC members. However, insufficient repair works are unfortunately often reported, and these works have potentially resulted in re-deterioration because more improvement is needed for inspection techniques to estimate the quality of repair and recovery.
\nDeveloping nondestructive testing and evaluation methods is strongly demanded for concrete structures to quantify or assure the repair and retrofit recovery. The International Union of Laboratories and Experts in Construction Materials, Systems, and Structures (RILEM) launched a technical committee on innovative NDT for repair and retrofit recovery [1]. Tomography techniques are studied based on elastic wave and acoustic emission (AE) to visualize, internal defects in three-dimension concrete with the committee’s activities. These techniques applicability has already been published in terms of elastic wave tomography [2, 3] and AE tomography [4, 5].
\nUsing parameters of elastic wave such as amplitudes and elastic wave velocities, internal distributions are obtained by the tomography technique. Elastic wave velocity is specifically used as the parameter in this study. Both the location of the excitation and the excitation time are known in the mentioned elastic wave tomography. On the other hand, they are unknown for AE tomography. The elastic wave velocity in each set-element over the structure can be calculated. Elastic wave velocity is theoretically associated with elastic modulus of material. The values would vary as low-velocity zones with the presence of such internal defects as cracks and voids.
\nIn a theory of elastic wave propagation inside media, the waves are reflected, diffracted, and scattered where it has voids and cracks. Elastic wave velocity is known to be decreased by the phase divergence. The zones of lower elastic wave velocity corresponding to those of heavier deterioration can be reasonable assumed. The distribution of wave velocities can be accordingly referred to as a good indicator of the internal condition of a concrete structure. Moreover, in order to guarantee whether the injected material is properly filled into cracks by using the crack injection method, the velocity distributions of elastic waves in the applicable regions of RC structures are estimated, before and after the repair, by employing AE tomography method [6].
\nThe repair effects in concrete were evaluated with 3D elastic wave tomography in the present study by means of innovative NDT, which can visually identify the outcome from the repair condition provided by the epoxy injection and patch repair methods. 3D tomography was employed for a 50-year-old concrete pier, which was repaired by epoxy injection method, as well as to a 53-year-old concrete wall, which was repaired by the patch repair method. And, AE tomography was applied to a 46-year-old RC slabs, in which epoxy-based resin was used as the injected material to repair the internal cracks.
\nAs described here, although the epoxy injection and patch repair methods are major repair methods even without the corrosion of the reinforcing bars, there are many reports indicating re-deterioration with insufficient repairs. This study aims to validate the 3D elastic wave tomography and AE tomography technique for inspection of the internal quality of concrete after repair.
\nConcrete pier specimen, 600 mm width, 1200 mm height, and 300 mm thickness, is shown in Figure 1. About 93 components of syringe-type caulking guns were set into pots for injection and 50 kHz resonance AE sensors were arrayed to receive elastic waves before the injection and 7 days after injection, which is corresponding to the epoxy resin hardening period.
\nOverview of concrete pier.
Attached AE sensors to four sides of the pier, as shown in Figures 2 and 12 sensors were arranged on sides A and B in a 600 × 1200 mm area and 4 sensors were installed on the other sides. About 25 mm diameter steel ball was used for the excitation of elastic wave. In order to identify the impact excitation time, at the closest sensor location, each excitation point was selected.
\nSensor arrangement.
Figure 3 shows concrete wall, 600 × 600 mm, where the patch repair method was applied, following V-shaped concrete removal was conducted for 80 mm depth and 120 mm width since surface cracks with water leakage were observed on the surface of the tunnel-lining concrete. Then, polymer cement mortar with a water-to-cement ratio W/C = 25% was used to fill the crack. Employing micro-core drilling and hammering as one-sided access measurement, the wave signals generated inside the concrete were detected. A 12 mm diameter micro-coring was performed up to 200 mm depth. A curved edge 6 mm diameter steel bar was inserted into the bit hole. The head of steel bar was hit by 25 mm diameter spherical steel ball. Hammering the steel bar without touching the hole wall, elastic waves could only be generated at the hole end in the depth direction. About 60 kHz resonance AE sensors were installed to detect the elastic waves. The sensor arrangements and excitation points are shown in Figure 4.
\nOverview of concrete wall.
Locations of drilling and sensor arrangement.
Figure 5 and Table 1 show a top view of an RC bridge, and specifications for the measured deck panels. This bridge is a municipal road bridge located in the Hokuriku region, Japan and it has been in service in the last 46 years. Three panels highlighted in the figure are selected for the measurement. On all of the slab panels, web-shaped cracks were sporadically evident on the concrete surface. These cracks are thought to be caused primarily by the alkali-silica reaction in concrete. Figure 6 shows a sketch of cracks obtained through visual inspection from the bottom side of the slab. This figure also shows the area of the tomography analysis for obtaining the velocity distribution. Crack widths are not indicated in figure, but in all the slab panels, the cracks width was smaller than 0.2 mm, and over almost the entire range, the widths were in the range of 0.10–0.15 mm.
\nA top side view of subject bridge.
Type | \nRC bridge (3 span composite girder bridge) | \n
---|---|
Length | \n88.0 m | \n
Age | \n46 years | \n
Thickness | \nSlab: 250 mm and asphalt: 50 mm | \n
Condition | \nWeb-shaped cracks were sporadically evident on the concrete surface. | \n
Bridge specifications.
Sketch of cracking.
In order to determine the velocity distributions by tomography, the following analytical steps are taken.
\nFirst, the arrival time at each sensor was determined with an Akaike Information Criterion (AIC) picker [7, 8]. For the digitized wave record xk of length N, the AIC value is defined as
\nwhere var(x[1, k]) indicates the variance between x1 and xk, and var(x[k, N]) is the variance between xk and xN.
\nThe point where AIC value minimizes, applying the least-square method, corresponds to the most suitable separation point of two series of stationary time, the arrival time as the phase onset is thus reasonably determined by the AIC picker. Lower AIC values suggest noise and higher AIC values show the arrival of wave signals. Following the determination of arrival time, the elastic wave velocity is calculated. The observed time of wave propagation Tobs is obtained by [9].
\nwhere Ts is the time of excitation and To is the arrival time.
\nThe reciprocal of the velocity is referred in the elastic wave tomography algorithm to as the “slowness.” As shown in Figure 7, slowness as the initial parameter is provided into each element. Travel time of elastic wave can be computed as elastic velocity is constant in individual element on this ray path. The total of the propagation time calculated by the slowness and the distance in each element (refer to Eq. (3)) derives the propagation time Tcal. The difference between the observed propagation time (Tobs) and the theoretical propagation time (Tcal) is obtained by Eq. (4).
\nwhere lj is the length crossing each element and sj is the slowness of each element.
\nSlowness for calculation of propagation time.
si is slowness of element i, li is length of the ray path in element i. Thus, it is revealed that li is essential for the calculation of the travel time.
\nIn order to reduce the difference between the observed propagation time and the theoretical propagation time, the slowness in each element is re-calculated and renewed. The total slowness correction is determined by Eq. (5) and the revised slowness is consequently calculated by Eq. (6).
\nwhere Li is the total distance of wave propagation through the i-element.
\nProceeding the iteration based on Eqs. (5) and (6) as shown in Figure 8, the optimal slowness, eventually the velocity, in each element corresponding to the observed propagation times of multiple paths over the interested area is determined as well as the velocity distribution.
\nAnalytical procedure for 3D tomography.
In order to determine the ray path more accurately, the ray trace algorithm is applied, taking into account detours of elastic waves due to the reflection and diffraction. Following 3D ray trace algorithm, which was proposed in previous research [3], the arrival time of each wave is obtained. Correction of the slowness in each element is carried out according to the error between the observed first travel time and computed value in the element, using 3D finite elements for meshing of target space in the present algorithm. Wave velocities between 2000 and 4500 m/s are given for the tomography results as the range of wave velocities in concrete.
\nAE tomography is a method for obtaining a velocity distribution by finding the travel time from an AE source to each sensor. Thus, it is necessary to obtain the position of the transmission source as accurately as possible. With the conventional ranging technique, which assumes that the propagation velocity is fixed, considerable errors are expected in the case that the tomography technique is applied to such a heterogeneous material as concrete. Consequently, a new ranging technique incorporating with the ray tracing concept has been developed as a pre-processing technique for AE tomography [6]. The ranging technique using ray tracing is illustrated in Figure 9. As shown in the diagram, ray tracing is performed from the received point j to all other nodes i, and the theoretical travel time Tji to each node is calculated. The shortest transmission time is determined from the differences between Tji and the initial travel time Tj at the received point j. The procedure is repeated for the number of received points N, and finally the node, where the variance of estimated arrival times estimated from Eqs. (7) and (8) becomes the minimal, is taken to be the transmission point. In Eq. (7), Tmi is the mean value of the estimated transmission times at each node i, and in Eq. (8), σi is the variance of the estimated transmission times at each node i.
\nOverview of transmission source estimation using ray tracing.
Figure 10 shows the model of AE tomography analysis and the positions of receiving sensors. The shaded part at the top of the model indicates the asphalt layer (thickness: 50 mm). Analyzed regions for slab panels 1 and 3 were set to be 3600 × 1900 mm. Concerning slab panel 2, there were limitations on the sensor positions, and thus the region was set to be 3600 × 1500 mm. As elements for AE tomography analysis, the applicable region was divided by 16 × 8 in total of 128 elements. In AE tomography, elastic waves were excited by the steel ball drop. A steel ball of 5 mm diameter was dropped at several locations for 12 minutes from the asphalt surface, consciously ensuring that the distribution of impact points was as uniform as possible at the target area. The steel ball dropping is illustrated in Figure 11. In AE tomography, the measurements were performed using an acceleration measurement system (TEAC). About 15 piezoelectric accelerometers with the frequency response from 3 Hz to 15 kHz were employed as receiving sensors. The point at which AIC is the minimum is determined as the arrival time of the wave. However, when the S/N ratio is low, it is difficult to identify the minimum value of AIC. Thus, a reliability parameter is developed for reading the initial travel time. The index is proposed as a measure for the identification of the rising edge of the wave [10]. It is found that readings of the initial travel times reasonably converge if the index is 0.05 or higher. In the present chapter, elastic waves with the index of 0.1 or higher are analyzed. AIC (kmin) indicates the minimum value of AIC, that is, corresponding to the initial travel time.
\nAnalysis model for AE tomography.
Steel ball dropping.
In order to investigate the epoxy-injected situation in damaged concrete, black light (ultraviolet light) was irradiated on the cored sample so that the injected material (epoxy resin) was colored in blue as shown in Figure 12. It is confirmed that epoxy resin was successfully injected into the concrete cover (up to 10 cm) and over the depth of the reinforcing bars (from 10 to 15 cm). The injected material can penetrate cracks even smaller than 0.1 mm in width [11].
\nResults of elastic wave tomography in 3D (left: before injection and right: after injection).
Figure 12 shows elastic wave tomography results before and after epoxy injection. The overview of injection repair method is shown in Figure 13. The wave velocities after the repair indicate clearly higher values than those before. The velocities are mostly higher than approximately 3000 m/s. This result implies that the epoxy injected from the surface of the pier could be filled and hardened sufficiently inside the media via cracks. However, at the central portions of the concrete pier, wave velocities are still lower than 2500 m/s, namely, the epoxy injection only guarantees the shallow zone repair from the concrete surface. The velocity distribution given by 3D elastic wave tomography shows the conditions inside the concrete, in particular, whether the epoxy is fully penetrated into the interior, while it is noted that the tomography technique could assess the repair level, which is not visually clarified on the exterior.
\nRepair by epoxy injection.
Figure 14 shows wave velocity histogram before and after the repair consequences. The mean value after the repair is higher than that before, and the variation decreases. Since the velocities lower than 2500 m/s are rarely observed in the histogram, concrete of the pier is repaired after the injection.
\nHistogram of wave velocities.
Figures 15 and 16 respectively show the tomography results the injected epoxy amount at Side A (referred as the front surface in Figure 12) and those at Side B (referred as the back surface in Figure 12). They are only the tomograms of wave velocities at the surface layer, comparing with the amount of epoxy injection. The injection pots which added syringe refilling are colored in red because the caulking guns were replaced and refilled with epoxy until the spring-loaded gun automatically stopped the injection.
\nResults of wave velocities and amount of epoxy injection (Side A).
Wave velocity and epoxy injection result (Side B).
The velocity distribution alteration reasonably correlates with the epoxy injection amount. Concrete property improvement suggested by the velocity recovery is also roughly confirmed with the epoxy injection amount.
\nVelocity-improved areas in Figures 15 and 16 are relatively observed in the areas, where additional injection was installed because of their porous media due to heavy deterioration (red colored in Figures 15(d) and 16(d)). Less improvement of the velocity are observed even after the repair at the bottom-right corner of side A (see Figure 15), where the method did not enable to penetrate the resin sufficiently into the concrete because of their lower connectivity of internal cracks.
\n3D elastic wave tomography technique mentioned above was challengingly applied to confirm patch repair effect for concrete wall of an existing structure. In this study, the technique was introduced as a method to evaluate the retrofit recovery. There is currently no NDT technique applicable in terms of in-situ measurement.
\nIntroducing micro-core drilling, excitation of elastic waves was driven. The technique is proposed and applied usefully for one-side access inspection works. Figure 17 shows the illustration of test procedure schematically.
\nProcedures of drilling and excitation.
On the surface of concrete wall with a surface crack (a), a V-cut concrete removal is performed (b), followed by a patch repair method with polymer cement mortar grouting (c), 12 mm diameter bit hole of 200 mm depth is drilled by micro-coring (d), at each concrete surface point. With the sensor array on the surface (e), 6 mm diameter a steel bar is inserted into the hole and the steel bar head is hit by a 25 mm diameter steel sphere ball.
\nCareful hammering at the steel bar head to prevent contacting the hole wall, the excited elastic waves were generated only from the bit hole bottom into the lining concrete, so that the excited signals were detected finally at sensors located on the concrete surface.
\nThe travel time along the steel bar was measured by two sensors as shown in Figure 18. AE sensor A records the excitation time at the head by using a steel ball of 15 mm diameter and the elastic wave travel time in the bar is calculated by detecting the arrival time of the wave at AE sensor B. The arrival time difference is 69 μs as shown in Figure 19.
\nMeasurement method of travel time in the steel bar.
Waveforms at excitation and receiver.
The dominant frequency of elastic wave excited by a 15 mm diameter steel ball is known as 19.4 kHz according to [12]. Considering a steel bar is used as wave guide, a frequency analysis was conducted for the waveforms observed at A and B. Figure 20 shows the frequency spectra. Each guided wave is detected via the 38 mm length steel bar. The dominant frequency was observed at A for 22.5 kHz and the dominant frequency was 16.6 kHz at B. Since these detected frequencies are higher than the resonant frequencies of the steel bar, first flexural mode (1.1 kHz), second flexural mode (3.2 kHz), and third flexural mode (5.4 kHz), respectively, as a cantilever, the principal components of the waveform were assumed to be generated as compression wave excited by the tapping at steel bar head.
\nFrequency spectra of waveforms at A and B.
The computation for wave velocity distribution in the targeted concrete wall was implemented by the tomography technique mentioned previously. Figure 21 shows the 3D distribution of wave velocities and Figure 22 shows them at cross section A.
\nDistribution of wave velocities in 3D.
Distribution of wave velocities at cross section A.
Although the triangle-shaped (dashed line) repair area has high velocity on the surface, the V-shaped low-velocity area is observed toward the bottom, whereas high-velocity zones exist at the left side of the specimen. The high velocity may indicate the intact condition of the original concrete quality, because the interested area is enough far from the repaired area.
\nThe repaired part is denoted by high velocity, in Figure 22, meanwhile the original concrete surrounding the patched area remarkably shows low velocity. The V-shaped area with low velocity underneath the repaired part could be potentially damaged by the chipping work for concrete removal. This is generally known and described in concrete surface treatment guideline prior to repairs and overlays [13, 14]. Further investigation is needed for the consideration in the influence of the hammer drill impact on damage to the concrete behind the removal zone.
\nFigure 23 shows the results of AE tomography, before and after repair by means of the crack injection. Results show that in all the slab panels, the velocity after repair exhibits increase compared to that before repair. Further quantitatively, the histograms of velocities obtained in all the elements are shown on the right side of the figure. For all slab panels, it is evident that the velocities at the elements clearly shift to the higher regions after repair. Due to the effectiveness of injected material in filling cracks and defects, detours and dispersions in the propagation paths of elastic waves are so eliminated that apparent velocities are increased.
\nResults of velocity distribution before and after repair.
All results imply that the velocity distribution obtained by the AE tomography method has a good potential to be an indicator for ascertaining the filled situation of injected material in a concrete slab. It is confirmed that the velocity for concrete which is not damaged shows about 3500 m/s to 4000 m/s. In some areas, however, velocities of about 2600 m/s are observed even after repair. This is because injected material might not be injected well into continuous cracks, independent air bubbles could be present due to the use of the air-entraining agent, and fine cracks at the interface between coarse aggregate are nucleated due to the alkali-silica reaction. As a result, there exists a possibility that the velocity recovery does not reach to the satisfactory level even after injection. On this issue, we plan to carry out a material test in the laboratory for confirmation.
\nDesign of the injection amount for the crack injection method could be based on the estimation of the crack widths, the depths, and the length measured. It is recognized that there exists no reasonable relationship between the amounts of designed injection and actual injection. Thus, an attempt to examine the amount of injected material is made from the results of AE tomography before repair.
\nIt is considered that the amount of injection should increase, depending on the extent of damage. Namely, if the degree of damage is small, the amount should decrease. In addition, if the damage is less than a certain degree, the injected material may not work well on the damage. On the other hand, if the elastic wave velocity could reflect the degree of damage, a correlation should be evident between the amount of injection and the values of velocities. Thus, the velocities are classified into grades, as given in Table 2. These quality indicators are proposed by Whitehurst [15]. They were determined from the relationship between mechanical properties and P-wave velocity in concrete. Following these indicators, the qualities before and after repair of the panels are classified as shown in Figure 24. It is found that the number of elements with Poor decreases, while that of Unacceptable keeps almost the same from before to after repair. As discussed before, due to the presence of air bubbles and the damaged interface with aggregates by alkali-aggregate reaction, the recovery of the velocities may not be apparent. These results imply that the region where the injected material could improve the quality of concrete is mostly that of Poor. It suggests that the repair by means of injection is effective for comparatively major damage. Figure 25 shows the relationship between total area of Poor estimated by AE tomography before repair and the actual amount of injection. As the Poor area increases, the increase in the actual amount of injection is clearly observed. Thus, it is possible to estimate the amount of injection before repair by carrying out the analysis using AE tomography.
\nVP (m/s) | \nQuality | \n
---|---|
>4570 | \nExcellent | \n
3660–4570 | \nFine | \n
3050–3660 | \nAcceptable | \n
2130–3050 | \nUnacceptable | \n
<2130 | \nPoor | \n
Quality indicator (Whitehurst).
Area ratio by quality before and after repair.
Total area (Poor) vs. injection amount.
Concrete pier, concrete wall, and slab were tested on the investigation on the internal damage assessment for the repair condition by applying elastic wave tomography and AE tomography. Determining the 3D velocity distribution, the repair effects of the epoxy injection method and the patch repair method were quantitatively evaluated. From the results, the following conclusions can be drawn in this study:
3D elastic wave tomography technique can evaluate the penetration of repair epoxy injection material and qualify the repair effect with the amount of injected rexin. 3D tomography technique installed with single-side access drill hammering successfully visualizes the internal quality of concrete after the patch repair method based on the elastic wave velocity distribution.
The velocity distribution obtained by AE tomography can serve as an indicator for ascertaining the state of crack and void filling with injected material. A good correlation is found between the low velocity region before repair and the amount of injected material. The results clearly show the potential for the AE tomography technique to be used as a method for estimating the performance of the crack injection method.
As mentioned previously, the RILEM committee was launched because innovative nondestructive inspection testing to qualify repair works is strongly required worldwide. We plan to continue studies based on the evaluation method using elastic wave tomography and accelerate its standardization.
\nThe various chemical transformations catalyzed by enzymes make these catalysts a key goal for utilization by the promising biotechnology industries. In the recent years, intense research in the field of enzyme technology has provided numerous approaches that facilitate the practical application of enzymes. This chapter emphasizes the application of oxidoreductases which catalyze the exchange of electrons amid the donor and acceptor molecules, in reactions involving electron transfer, proton/hydrogen extraction, hydride transfer, oxygen insertion, or other imperative steps. Oxidoreductases acquire advantage from the inclusion of different cofactors - for instance heme, flavin and metal ions - to catalyze redox reactions [1]. Majority of oxidoreductases are nicotinamide cofactor-dependent enzymes which have a high preference for nicotinamide adenine dinucleotide phosphate (NADP) or nicotinamide adenine dinucleotide (NAD) and they are further classified in six major classes which are oxidases, dehydrogenases, hydroxylases, oxygenases, peroxidases and reductases [2]. This chapter demonstrates the potential applications of oxidoreductases on the growth of oxidoreductase-based diagnostic tests and better biosensors, in the design of inventive systems for crucial coenzymes regeneration, and in the formation of oxidoreductase-based approaches for synthesis of polymers and oxyfunctionalized organic substrates.
The diagnosis and monitoring of a variety of diseases is extremely demanding nowadays for routine examination of clinical samples and other associated tests. The diagnostic enzymes are used for the detection/diagnosis or prognosis of disease conditions due to their substrate specificity and quantitated activity in the presence of other proteins, and are preferred in diagnosis, which can be used as a diagnostic tool for disease detection [3]. Depending on the verity of the disease, diseased state often leads to tissue damage. In such conditions, enzymes specific to diseased organs are released into blood circulation with augmented enzyme activity. The measurement of corresponding enzyme activities in blood/plasma, or any other body fluid, has been exploited in the diagnosis of diseased tissues/organs [3].
Jixu Wang et al. [4] investigated the expression and significance of glucose-6-phosphate dehydrogenase (G6PD) in human gastric cancer progression and prognosis. Apoptosis and necrosis are two major types of cell death in normal and disease pathologies. A key signature for necrotic cells is the permeabilization of the plasma membrane which can be quantified in tissue culture settings by measuring the release of the intracellular enzyme lactate dehydrogenase (LDH). It has been described that the measuring LDH release is a useful method for the detection of necrosis [5]. Two dehydrogenases, specifically, sorbitol dehydrogenase (SDH) and LDH, are used for cancer prognosis [3]. Reports suggested that in prostate cancer [6], and precancerous colorectal neoplasms [7], an abnormal serum concentration of SDH has been observed. Additionally, an enhanced level of SDH can be observed in acute liver damage and parenchymal hepaticdiseases [3]. It has been reported that LDH, marker of anaerobic metabolism, is associated with highly invasive and metastatic breast cancer and suggested that the association of activity of LDH in tumor tissue with mammographic characteristics could help in defining aggressive breast cancers [8]. The gene expression of LDH is studied in several human malignant tumors, collectively among colorectal cancer [9], lung cancer [10, 11, 12], breast cancer [13], oral cancer [14], prostate cancer [15], germ cell cancer [16], and pancreatic cancer [17]. In recent times, the prognostic value of the serum LDH level in cancer patients has been considered as a significant area of research. Additionally, LDH performs as a prognostic marker in patients with acute leukemia [18] and sickle cell disease [19].
A biosensor is an analytical tool that comprises a biological or biologically derived sensing matter with close proximity to the physico-chemical transducer [3]. The chief function of such a device is to produce a discrete or uninterrupted signal that is comparative to the concentration of the analyte [20]. Enzyme-based chemical biosensors are based on biological recognition and in order to function, the enzymes must be accessible to catalyze a specific biochemical reaction and be stable under the normal operating circumstances of the biosensor [21]. Generally the function of oxidoreductase biosensors is dependent on charge transport amid the enzyme and an electrode surface by means of coenzymes or redox mediators [22].
Over the years, various enzyme-based biosensors have been developed, however only a few of them are commercialized. The majority of the published work on enzymatic biosensors focuses on targeted blood glucose monitoring based on amperometric techniques [3]. The earliest glucose biosensor based on glucose dehydrogenase from Erwinia sp. and carbon paste was generated by Laurinavicius et al. [23] where the enzyme was incorporated in a polylysine-albumin gel, and the anchoring material was a paste of chemically adapted carbon powder, fumed silica, and binding material. A cellulose dehydrogenase based glucose biosensor from a mutant of Corynascus thermophilus has been developed, and a glassy carbon electrode (GCE) was acquired by direct electrode position of gold nanoparticles (AuNPs). The biosensor was used for the detection of glucose in human saliva samples, with successful results in terms of both revival and association with glucose blood levels [24]. This proposes the development of noninvasive glucose monitoring devices. The details of different oxidoreductase enzymatic biosensors applied for clinical diagnosis are listed in Table 1. The first marketable biosensor (glucose biosensor) was commenced in 1975 which was derived from the electrochemical recognition of hydrogen peroxide, and the glucose oxidase was employed for the improvement of the biosensor [3]. Subsequently, Clemens et al. [25] established a novel amperometric glucose biosensor in a bedside artificial pancreas, and it was marked underneath the brand name “Biostator” by Miles (Elkhart, Indiana).
Enzymes | Analyte | Test sample | Disease diagnosed | References |
---|---|---|---|---|
Glucose oxidase | Glucose | Blood plasma, blood serum, urine, and saliva | Diabetes, hypoglycemia | [26, 27, 28, 29] |
Oxalate oxidase | Oxalate | Blood serum and urine | Idiopathic urolithiasis and various intestinal diseases | [30] |
Cholesterol oxidase | Cholesterol | Blood serum | Coronary heart disease, myocardial and cerebral infarction (stroke) | [31, 32, 33, 34] |
Lactate oxidase | Lactate | Blood plasma, blood serum, drug and biological samples | Hyper lactatemia, cardiac arrest, resuscitation, sepsis, reduced renal excretion, decreased extra hepatic metabolism, intestinal infarction and lacticacidosis | [35, 36, 37, 38, 39, 40] |
Oxidoreductase enzymatic biosensors as diagnostic tools.
The most of oxidoreductases for catabolism and anabolism significantly require two natural nicotinamide-based coenzymes (NAD and NADP), respectively. The most NAD(P)-dependent oxidoreductases choose one coenzyme as an electron acceptor or donor to the other depending on their diverse metabolic functions [41]. Generally coenzymes are involved in these oxidoreductase-catalyzed reactions to transport
Nicotinamide coenzymes based dehydrogenases are of emergent importance for the production of chiral compounds, either by reduction of a prochiral precursor or via oxidative resolution of their racemate [45]. Nevertheless, the oxidized and reduced nicotinamide cofactors regeneration is an extremely critical step as the employ of these cofactors in stoichiometric amounts is too expensive for function. There are very few enzymes which are appropriate for the regeneration of oxidized nicotinamide cofactors. Glutamate dehydrogenase can be utilized for the oxidation of NADH in addition to NADPH while l-lactate dehydrogenase is able to oxidize NADH only [45]. The reduction of NAD+ is carried out by formate and FDH [45]. Glucose-6-phosphate dehydrogenase and glucose dehydrogenase are proficient to reduce both NAD+ and NADP+ [45]. It has been reported that ADH from horse liver reduces NAD+ whereas ADHs from Lactobacillus strains catalyze the reduction of NADP+ [45]. These enzymes can be applied by their inclusion in entire cell biotransformations by an NAD(P)+-dependent major reaction to achieve in situ regeneration of the consumed cofactor [45]. And for the regeneration of the reduced cofactors NADH and NADPH numerous systems for instance engineered formate dehydrogenase [46, 47], phosphite dehydrogenase [48, 49], glucose dehydrogenase [50, 51] plus cosubstrate are well established and extensively used.
Johannes et al. [52] reported the engineering of a highly stable and active mutant phosphite dehydrogenase (12x-A176R PTDH) from Pseudomonas stutzeri and evaluation of its potential as an effective NADPH regeneration system in an enzyme membrane reactor. They have utilized two practically imperative enzymatic reactions including xylose reductase-catalyzed xylitol synthesis and alcohol dehydrogenase-catalyzed (R)-phenylethanol synthesis as models, and the mutant PTDH was compared to the commercially available NADP+-specific Pseudomonas sp. 101 formate dehydrogenase (mut Pse-FDH) that is extensively employed for NADPH regeneration [52]. Soluble water-forming NAD(P)H oxidases comprise a promising NAD(P)+ regeneration scheme since they only require oxygen as cosubstrate and produce water as only byproduct [53]. In addition, the thermodynamic equilibrium of O2 reduction is a significant driving force for mostly energetically unfavorable biocatalytic oxidations [53]. Petschacher et al. [53] presented the generation of an NAD(P)H oxidase with high activity for both cofactors, NADH and NADPH. Applicability for cofactor regeneration is shown for coupling with alcohol dehydrogenase from Sphyngobium yanoikuyae for 2-heptanone production.
Enzyme catalyzed oxidation reactions have achieved growing concern in biocatalysis recently, reflected also by numerous outstanding reviews on this topic reported in the last years [54, 55, 56]. The group of oxidoreductases, to which all enzyme catalyzing oxidoreduction reactions, comprises numerous groups of biocatalysts such as dehydrogenases, monooxygenases, dioxygenases, oxidases, peroxidases, etc. [55]. Moreover, the enzymatic oxidative polymerizations have advantages of using nontoxic catalysts and mild reaction conditions, and the specific enzyme catalysis affords regio- and chemoselective polymerizations to construct functional materials [57]. It has been reported that peroxidases with the use of hydrogen peroxide as oxidant efficiently induce the oxidative coupling of phenols to phenolic polymers, the majority of which are scarcely attained by conventional chemical catalysts [57]. In addition, it has been published that laccase and peroxidase are helpful for production of cross-linked polymers such as artificial urushi and biopolymer hydrogel [57]. Kobayashi [58] established that the enzymatic polymerization as to be an efficient method of polymer synthesis. The polymerization uses hydrolases and oxidoreductases as catalysts and this new method of polymer synthesis afforded natural polysaccharides like cellulose, amylose, xylan, and chitin, and unnatural polysaccharides catalyzed by a glycosidase from well-designed monomers, varied functionalized polyesters catalyzed by lipase from a variety of monomers, and poly-aromatics materials catalyzed by an oxidoreductase and an enzyme model complex from phenols and anilines [58]. Furthermore, vinyl polymerization has been initiated by oxidoreductase [58].
Marjanovic et al. [59] reviewed the oxidative oligomerization and polymerization of various arylamines, e.g., aniline, substituted anilines, aminonaphthalene and its derivatives, catalyzed by oxidoreductases, such as laccases and peroxidases, in aqueous, organic, and mixed aqueous organic monophasic or biphasic media. Owing to the nontoxicity of oxidoreductases and their elevated catalytic effectiveness, as well as high selectivity of enzymatic oligomerizations/polymerizations under gentle conditions by means of primarily water as a solvent and often resulting in minimal byproduct formation enzymatic oligomerizations and polymerizations of arylamines are environmentally friendly and considerably contribute to a “green” chemistry of conducting and redox-active oligomers and polymers [59].
It has been also established that oxidative enzymes comprise privileged catalysts in organic synthesis [60]. Environmentally benign reaction conditions with high selectivity are the most fascinating characteristic exhibited by these biocatalysts in contrast to classical metal-based reagents. de Gonzalo et al. [60] reviewed the new perspectives and concepts derived from oxidative enzymatic processes, involving oxidative C-C bond forming reactions, atroposelective oxidations, oxidative dynamic processes, interconnected reactions, cyclic deracemizations, oxidative desymmetrizations and artificial oxidative enzymes. Oxidoreductases comprise an imperative group of biocatalysts as they facilitate not merely the broadly used stereoselective reduction of aldehydes and ketones but also the less well exploited oxidation of alcohols and amines [53]. In addition, oxidoreductases catalyzed oxidations are utilized for production of chiral alcohols and amines by deracemization [54, 60, 61, 62]. It has been reviewed thoroughly that the oxidoreductases enable chemists to perform highly selective and efficient transformations ranging from simple alcohol oxidations to stereoselective halogenations of non-activated C-H bonds [63]. Mifsud et al. [64] demonstrated for the first time that catalytic water oxidation mediated by robust TiO2 semiconductors can be productively coupled to oxidoreductases achieving photobiocatalytic redox reactions.
One of the major applications of oxidoreductase is a pharmaceutical synthesis of 3,4-dihydroxylphenyl alanine (DOPA), which is employed in the treatment of Parkinson’s disease and the industrial process that synthesizes DOPA make use of the oxidoreductase polyphenol oxidase [65]. It has been reported that the enantioselective reduction of C-4-substituted 3,5-dixocarboxylates can be carried out by using alcohol dehydrogenase from Lactobacillus brevis (LBADH) over-expressed in E. coli [66]. Laccase can be employed to synthesize numerous complex medicinal agents including triazolo(benzo)cycloalkyl thiadiazines, vinblastine, penicillin X dimer, cephalosporin antibiotics, and dimerized vindo-line [67]. In addition laccase can be used to synthesize a range of functional organic compounds including polymers with specific mechanical/electrical/optical properties, textile dyes, cosmetic pigments, flavor agents, and pesticides [68]. Biocatalysis is facilitating technology to organic synthesis chemistry by providing high selectivity of enzymatic reactions under mild conditions makes it a very valuable tool for green chemistry.
Due to the specificity and bio-based nature, potential applications of oxidoreductases in various fields are attracting active research efforts [69]. Several products generated by oxidoreductases are finding applications as antimicrobial, detoxifying, or active personal-care agents [69]. One potential application is laccase-based in situ generation of iodine, a reagent extensively used as disinfectant [67]. It has been described that laccase-iodide salt binary iodine-generating system (for sterilization) can have several advantages over the direct iodine application [69]. Peroxidases may replace laccase for the application, even though they would require H2O2 as cosubstrate [69]. The ClO¯ and Mn(III) species formed by haloperoxidase and Mn-peroxidase are extremely effective oxidants and antimicrobial agents [70]. Peroxidase can also be used to cross-link collagen which is beneficial to the healing of damaged skin [71]. The physiological activities of lysyl oxidase comprise the extracellular matrix construction which can hasten wound-healing [72, 73]. A glucose oxidase, lactoperoxidase, and iodide system has been tested for dental care and the oxidase produces H2O2 to feed the peroxidase, so that it can produce iodine that can kill plaque-causing bacteria [74]. It has been reported that the haloperoxidase can be used to oxidatively modify rubber latex surfaces, making them less allergenic [75]. A secreted oxidoreductase may even be developed as a vaccine against secretor microbes such as, Aspergillus oryzae catalase A protein has been studied as a potential aspergillosis vaccine [69]. It has been reported that low-molecular-mass laccase purified from the mushroom Tricholoma giganteumis possesses significant HIV-1 reverse transcriptase inhibitory activity [76]. As nature’s own catalysts, enzymes acquire very diverse specificity, reactivity, and other physicochemical, catalytic, and biological properties highly enviable for miscellaneous industrial and medical applications [69].
Tremendous progress has been made in the recent years in the field of applications of oxidoreductases. Oxidoreductases metabolism is a fundamental bio-process that plays a pivotal role in all species, including humans, plants, animals, and microorganisms, as their specific function is to catalyze oxidation and reduction reactions that occur within the cell. Abnormality in this metabolic system leads to a number of metabolic disorders. Thus, owing to the remarkable properties of oxidoreductases, they can be used for the diagnosis of disorders. They can provide insight into the diseased state by diagnosis, prognosis, or by assessment of response therapy. It has been established that oxidoreductases as biosensors are becoming popular potential tools in biotechnology due to their high specificity. With oxidoreductases, the conversion of a variety of aliphatic/aromatic molecules can be achieved; inert hydrocarbons can be functionalized (by hydroxylation, sulfoxidation, epoxidation, etc.); regio-, enantio- (on racemic substrates); enantiotopo– (on prochiral sub-strates); and chemo-selective reactions can be accomplished; important synthons from inexpensive and renewable biomaterials can be constructed; and the negative environment impact can be reduced [69]. Since numerous chemical and biochemical transformations engage oxidation/reduction processes, developing practical biocatalytic applications of oxidoreductases has long been an imperative target in biotechnology.
The author gratefully acknowledges the Department of Chemistry, Goalpara College (Assam), India.
The author declares no conflict of interest.
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The CC BY 3.0 license permits Works to be freely shared in any medium or format, as well as the reuse and adaptation of the original contents of Works (e.g. figures and tables created by the Authors), as long as the source Work is cited and its Authors are acknowledged in the following manner:
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\\n\\nThe same principles apply to Works published under the CC BY-NC-SA 3.0 license, with the caveats that (1) the content may not be used for commercial purposes, and (2) derivative works building on this content must be distributed under the same license. The restrictions contained in these license terms may, however, be waived by the copyright holder(s). Users wishing to circumvent any of the license terms are required to obtain explicit permission to do so from the copyright holder(s).
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\\n\\nAll rights to Books and all other compilations published on the IntechOpen platform and in print are reserved by IntechOpen.
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\\n\\nPolicy last updated: 2016-06-08
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Copyright is the term used to describe the rights related to the publication and distribution of original Works. Most importantly from a publisher's perspective, copyright governs how Authors, publishers and the general public can use, publish, and distribute publications.
\n\nIntechOpen only publishes manuscripts for which it has publishing rights. This is governed by a publication agreement between the Author and IntechOpen. This agreement is accepted by the Author when the manuscript is submitted and deals with both the rights of the publisher and Author, as well as any obligations concerning a particular manuscript. However, in accepting this agreement, Authors continue to retain significant rights to use and share their publications.
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\n\nWork - a Chapter, including Conference Papers, and any and all text, graphics, images and/or other materials forming part of or accompanying the Chapter/Conference Paper.
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LICENSE | \n\t\t\tUSED FROM - | \n\t\t\tUP TO - | \n\t\t
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The CC BY 3.0 license permits Works to be freely shared in any medium or format, as well as the reuse and adaptation of the original contents of Works (e.g. figures and tables created by the Authors), as long as the source Work is cited and its Authors are acknowledged in the following manner:
\n\nContent reuse:
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\n\nRepublishing – More about Attribution Policy can be found here.
\n\nThe same principles apply to Works published under the CC BY-NC-SA 3.0 license, with the caveats that (1) the content may not be used for commercial purposes, and (2) derivative works building on this content must be distributed under the same license. The restrictions contained in these license terms may, however, be waived by the copyright holder(s). Users wishing to circumvent any of the license terms are required to obtain explicit permission to do so from the copyright holder(s).
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\n\nAll rights to Books and all other compilations published on the IntechOpen platform and in print are reserved by IntechOpen.
\n\nThe copyright to Books and other compilations is subject to separate copyright from those that exist in the included Works.
\n\nAll Long Form Monographs/Compacts are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others.
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\n\nThere must be an Attribution, giving appropriate credit, provision of a link to the license, and indication if any changes were made.
\n\nNonCommercial - The use of the material for commercial purposes is prohibited. Commercial rights are reserved to IntechOpen or its licensees.
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\n\nContent reuse:
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\n\nOriginally published in {full citation}. Available from: {DOI}
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\n\nAll Video Lectures under IntechOpen's production are subject to copyright and are property of IntechOpen, unless defined otherwise, and are licensed under the Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. This grants all others the right to:
\n\nShare — copy and redistribute the material in any medium or format
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\n\n© {year} IntechOpen. Published under CC BY-NC-ND 4.0 license. Available from: {DOI}
\n\nUsers wishing to reuse, modify, or adapt the Video Lectures in a way not permitted by the license are welcome to contact us at permissions@intechopen.com to discuss waiving particular license terms.
\n\nAll software used on the IntechOpen platform, any used during the publishing process, and the copyright in the code constituting such software, is the property of IntechOpen or its software suppliers. As such, it may not be downloaded or copied without permission.
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\n\nPolicy last updated: 2016-06-08
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