These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\n
This collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\n
To celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\n
Initially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\n
This collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\n
To celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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\r\n\tCryptococcosis, caused by the opportunistic yeast Cryptococcus neoformans or Cryptococcus gattii is an important cause of morbidity and mortality in persons immunocompromised by advanced HIV disease. Cryptococcal meningitis is the leading cause of meningitis among adults with sub-Saharan Africa. In addition, C. gattii has been responsible for major outbreaks in North America. There is a growing interest in the epidemiology of cryptococcal infection and disease in HIV-negative individuals, particularly in those with poorly controlled diabetes mellitus and recipients of solid organ transplants.
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\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art in cryptococcosis and its etiologic agent Cryptococcus, featuring original research and up-to-date reviews that focuses on the most important evidence-based developments in this critically important area.
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1. Introduction
Coumarin (2H-chromen-2-one) derivatives have spawn great interest over the years because of their significant biological importance [1]. They are associated with various biological activities viz. antiviral [2, 3], antibacterial [4, 5], antimicrobial [6], anticoagulant [7], anti-inflammatory [8, 9], anticancer [10, 11], anticonvulsant [12], antioxidant [13], antifungal [14, 15], and anti-HIV [16]. They also possess the properties like inhibition of platelet aggregation [17] and inhibition of steroid 5α-reductase [18]. Besides, they are attracting considerable attention of chemists due to their wide range of applications such as optical brighteners [19], photosensitizers [20], fluorescent and laser dyes [21], and additives [22] in food, perfumes, cosmetics, and pharmaceuticals. The novel compounds are also utilized in drug and pesticidal preparations [23]. Considering these multifarious activities of coumarins, synthetic chemists are actively engaged in developing new and superior methods for the isolation of coumarin derivatives. The most widely used method for their synthesis is Pechmann reaction [24, 25, 26, 27], which involves the condensation between phenols and β-keto esters, in the presence of an acid catalyst. This method employs both homogeneous catalysts such as concentrated H2SO4 [24, 25], trifluoroacetic acid (TFA) [28], and Lewis acids (LA) such as AlCl3 [29], ZnCl2 [30], ZrCl4 [31], TiCl4 [32], etc. and heterogeneous catalysts such as cation-exchange resins [33], Nafion resin/silica composites [34], zeolite H-BEA (H-beta, SiO2/Al2O3 = 14) [35], and other solid acids.
2. Methods to synthesize coumarin derivatives
2.1 Pechmann condensation reaction
The general reaction sequence of Pechmann reaction and its mechanism, shown in Figure 1, involves an esterification/transesterification between the phenol 1 and β-keto ester 2 in the presence of protonic acid or Lewis acid (LA) catalyst to produce species 4 followed by an attack to the activated carbonyl carbon by the aromatic ring at ortho-position to yield the new ring in species 5. Finally, dehydration of species 5 affords coumarin derivative 2.
Figure 1.
Mechanism for the acid-catalyzed Pechmann condensation.
A series of substituted coumarins 8 have been synthesized in 25–77% yields by the reactions of substituted phenols 6 with ethyl acetoacetate 7 in the presence of zinc-iodine mixture in refluxing toluene (Figure 2) [36]. It is observed that phenols containing electron-donating substituent like ▬CH3 group result in higher yields compared to unsubstituted phenols and phenols having electron-withdrawing group such as NO2 group.
Figure 2.
Synthesis of substituted coumarins.
When 3-(N,N-dimethylamino)phenol 9 is subjected to react with ethyl 2-acetamide-3-oxobutyrate 10 in the presence of anhydrous ZnCl2 in absolute ethanol under reflux condition, the acetamido coumarin 11 is obtained only in 12.4% yield (Figure 3) [30].
Figure 3.
Synthesis of acetamido coumarin.
Substituted coumarins 14 have been achieved in moderate to good yields from substituted phenols 12 and methyl acetoacetate 13 under conventional and microwave heating, respectively, catalyzed by concentrated H2SO4 (Figure 4) [37]. It is found that the reactions using the latter method are faster coupled with product in better yields compared to former one.
Figure 4.
Synthesis of substituted coumarins.
Synthesis of substituted coumarins 16 in 62–98% yields has also been described by Maheswara et al. [38] via reactions of substituted phenols 1 with β-keto esters 15 in the presence of a heterogeneous catalyst, HClO4.SiO2 under solvent-free conditions (Figure 5, Condition A). The aforementioned method involves recoverable cheap catalyst and shorter reaction time with high product yields. However, relatively lower yields (35–55%) of substituted coumarins 16 have been isolated from the similar starting precursors catalyzed by Amberlyst-15 acidic catalyst [39] in toluene under refluxing condition (Figure 5, Condition B).
Figure 5.
Synthesis of substituted coumarins.
Pechmann condensation reactions for the synthesis of substituted coumarins using various homogeneous and heterogeneous catalysts have been reported in literature and some important ones are summarized in Table 1.
Table 1.
Synthesis of substituted coumarins via Pechmann condensation reactions.
From Table 1, it is quite evident that the reactions under microwave as well as ultrasound irradiation occur at a faster rate than those of the conventional methods (entries 10, 14, 15, 16, 25, 31, 32, and 39). Unsubstituted phenol produces lower yields of corresponding coumarin derivatives and/or requires longer reaction time (entries 2–4, 7, 10, 12, 13, 24, 28, 30, and 38), higher temperature (entries 2, 3, 7, and 12), and excess amount of catalysts (entries 7 and 12) than di- and trihydric phenols. This may presumably be due to the less reactivity of unsubstituted phenol toward Pechmann condensation reaction compared to di- and trihydric phenols. In addition, the substitution of an electron-donating group such as m/p-Me or p-OMe in the phenols leads to decrease of catalytic activity and, hence, requires longer reaction time and/or gives rise to lower yields of products (entry 13). The reactivity of monohydric phenols having electron-withdrawing groups such as m-NH2 and m-OMe is also lowered compared with simple di- and trihydric phenols (entries 19, 28, and 37). 1-Naphthol and 2-naphthol need longer reaction time (entries 13, 33, and 39) and/or furnish products with lower yields (entries 13, 37, and 40) compared to other phenols, due to the presence of another phenyl ring. However, better yield of benzocoumarin is obtained from the reaction between 1-naphthol and more reactive β-keto ester, ethyl 4-chloro-3-oxobutanoate (entry 37). It is interesting to note that β-keto ester having phenyl group at the β-position such as ethyl 3-oxo-3-phenylpropanoate is found to be less reactive in Pechmann condensation with resorcinol and 1,3-dihydroxy-5-methyl benzene due to the presence of conjugated keto center, which lengthens the reaction time than in the reactions of EAA and/or ethyl 4-chloro-3-oxobutanoate with resorcinol and 1,3-dihydroxy-5-methyl benzene (entries 21, 28, and 37). Besides, the reactivity of different types of phenols and β-keto esters, catalyst efficiency, and solvent effect of Pechmann condensation has also been studied. It is observed that TiCl4 (entry 5) is the most effective catalyst as far as reaction time is considered, whereas montmorillonite K-10 (entry 1) and sulfated zirconia (SZr) (entry 9) are found to be less effective. Ionic liquids (ILs) such as 1-butyl-3-methylimidazolium hexafluorophosphate [bmim]PF6 and 1,3-disulfonic acid imidazolium hydrogen sulfate (DSIMHS) have been used as effective and reusable catalysts and reaction media as well (entries 6 and 18).
Lewis acid−surfactant-combined catalyst (LASC) such as nano-TiO2 on dodecyl-sulfated silica support (NTDSS) is used as a reusable and highly effective catalyst for Pechmann condensation of phenols containing different types of substituents in water led to excellent product yields (entry 20). Other recyclable solid acid catalysts have also been employed in Pechmann condensation reactions leading to coumarin derivatives in good to excellent yields under solvent-free (entries 22–24, 26–27, 29–30, and 42), microwave irradiation (entry 25) and/or ultrasound irradiation (entry 39) conditions.
More importantly, sulfonic acid-supported silica-coated magnetic nanoparticles (Fe3O4@SiO2@PrSO3H), CuFe2O4 nanoparticles, and zirconium(IV) complex grafted silica coated magnetic nanoparticles are found to be the most efficient catalysts toward Pechmann condensation, in which case the catalyst can be effortlessly separated by external magnet after completion of the reaction and reused for 22, 6, and 5 consecutive runs, without any significant loss in catalytic efficiency (entries 33–35).
Pechmann condensation of pyrogallol and resorcinol with ethyl acetoacetate over nanosponge MFI zeolite in comparison with conventional zeolites (MFI, BEA, and USY) and other layered MFI (lamellar, pillared, and self-pillared) have been investigated. It is important to note that the nanosponge catalysts exhibit the best catalytic performance with respect to the products’ selectivity in the liquid-phase condensation reactions among all the investigated zeolites (entry 36).
On the other hand, the catalytic behavior of metal–organic frameworks such as Cu-benzene-1,3,5-tricarboxylate (CuBTC) and Fe-benzene-1,3,5-tricarboxylate (FeBTC) is investigated and compared with large-pore zeolites, beta (BEA), and ultrastable Y (USY) (entry 41). It is clear that zeolites BEA and USY are found to be more active catalysts in transformations of the most active substrates like resorcinol and pyrogallol but a low conversion of naphthol is observed. However, almost total transformation of naphthol (93–98% conversion) to the target product occurs within 23 h of the reaction time over metal–organic frameworks, CuBTC and FeBTC. Catalytic activity of many other catalysts under different reaction conditions is delineated in the recently published review [80].
2.2 Knoevenagel condensation reaction
An efficient green one-pot synthetic method for the synthesis of 3-substituted coumarin derivatives 21/22 has been observed by Knoevenagel condensation of various o-hydroxybenzaldehydes 18/19 with 1,3-dicarbonyl compounds 20 using nano-ZnO catalyst under microwave or thermal conditions, which affords moderate to good yield of the products (Figure 6) [81]. Reactions under microwave-irradiation conditions are found to be more convenient than thermal conditions.
Figure 6.
Synthesis of 3-substituted coumarins.
Various coumarin-3-carboxylic acid derivatives 25/26 have been synthesized in good yields using catalytic amounts of SnCl2.2H2O under solvent-free condition (Figure 7) [82].
Figure 7.
Synthesis of coumarin 3-carboxylic acid derivatives.
Ultrasound irradiation technique is also useful to synthesize 3-aryl coumarin derivatives. Treatment of o-hydroxybenzaldehydes 18 with aryl substituted acetyl chloride 27 in the presence of K2CO3 as a catalyst in tetrahydrofuran (THF) using ultrasound irradiation leads to the formation of 3-aryl coumarin derivatives 28 in moderate to high yields (Figure 8) [83]. This green method appears to be a convenient and simple pathway than that of conventional heating.
Figure 8.
Synthesis of 3-aryl coumarin derivatives.
Coumarin-substituted benzimidazole or benzoxazole derivatives 32 that are known as coumarin dyes have been synthesized in good yields from 4-diethylamino-2-hydroxybenzaldehyde 29, ethyl cyanoacetate 30, and ortho-phenylenediamine/phenylenehydroxyamine derivatives 31 in the presence of reusable green solid acid like HZSM-5 zeolite, heteropoly acids, e.g., tungstophosphoric acid (H3PW12O40), and/or tungstosilicic acid (H4O40SiW12) in n-pentanol or water and even solvent-free conditions (Figure 9) [84].
Figure 9.
Synthesis of coumarin-substituted benzimidazoles/benzoxazoles.
Cellulose sulfonic acid (CSA) is an efficient catalyst for the synthesis of 3-substituted coumarin via Knoevenagel condensation reaction. Thus, 3-acetyl coumarin 34 is obtained in 88% yield in the reaction between salicylaldehyde 33 and ethyl acetoacetate 7 in the presence of CSA under solvent-free conditions (Figure 10) [85].
Figure 10.
Synthesis of 3-acetyl coumarin.
Shaabani et al. [86] have described the synthesis of 3-substituted coumarins 21 in good yields via Knoevenagel condensation of 2-hydroxybenzaldehydes 18 with β-dicarbonyl compounds 35 in the presence of a recyclable ionic liquid 1,1,3,3-N,N,N′,N′-tetramethylguanidinium trifluoroacetate (TMGT) under thermal heating (Figure 11, Condition A) and/or microwave irradiation conditions (Figure 11, Condition B). 3-Substituted coumarins 21 are also synthesized from similar starting precursors using the 1,3-dimethylimidazolium methyl sulfate [MMIm][MSO4] ionic liquid in the presence of L-proline as an additional promoter under heating condition (Figure 11, Condition C) [87].
Figure 11.
Synthesis of 3-substituted coumarins.
Imidazolium based phosphinite ionic liquid (IL-OPPh2) catalyzed synthesis of 3-substituted coumarin derivatives has been reported in literature; when o-hydroxy benzaldehydes 18 are treated with active methylene containing compounds 35 in the presence of IL-OPPh2 catalyst at 60°C, 3-substituted coumarin derivatives are obtained in moderate to good yields (Figure 12) [88]. TSIL plays both the reaction media and catalyst as well.
Figure 12.
Synthesis of 3-substituted coumarins.
Reactions of o-hydroxybenzaldehydes 18 with activated methylene compounds 35 catalyzed by Bronsted acid ionic liquid (BAIL) and 1-(4-sulfonic acid)butyl-3-methylimidazolium hydrogen sulfate [(CH2)4SO3HMIM][HSO4] in water lead to 3-substituted coumarin derivatives in good yields (Figure 13) [89].
Figure 13.
Synthesis of 3-substituted coumarins.
Synthesis of substituted coumarins via Knoevenagel condensation using various organic catalysts such as piperidine, ammonia, L-lysine, L-proline, benzoic acid, etc. has been reported in literature and some are summarized in Table 2.
Table 2.
Synthesis of substituted coumarins via Knoevenagel condensation reactions.
It is quite evident that in Table 2 several methodologies for the synthesis of substituted coumarins using different organic catalysts are established. Among these, L-proline-catalyzed reactions offer high yields (entry 3), which explains synthesis of 3-substituted coumarins by the condensation of o-hydroxybenzaldehydes with a variety of active methylene compounds catalyzed by 1,3-dimethyl imidazolium methyl sulfate [MMIm][MSO4] and L-proline. Another L-proline-catalyzed synthesis of coumarins is known, but in that case, the yield is very poor (entry 4). Similar result is also observed under L-lysine-catalyzed synthesis of coumarins (entry 5).
A series of 3-phenyl substituted coumarin analogues have been achieved via a two-step process involving esterification using 1,1-carbonyldiimidazole (CDI) followed by condensation reaction in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) under mild conditions (entry 1).
Microwave-assisted synthesis of coumarins is also known, which not only reduces the reaction time but also increases the yields of the products (entries 2, 6, and 7).
Benzocoumarin derivatives have been synthesized from 1-hydroxy-4-methyl-naphthalene-2-carbaldehyde and compounds containing active methylene group via piperidine-catalyzed Knoevenagel condensation reaction (entry 8). Moreover, benzothiazolyl coumarins with isothiocyanate functionality have been synthesized from commercially available 2-hydroxy-4-nitro benzoic acid in the presence of piperidine in ethanol (entry 9).
Application of sonochemistry for the synthesis of different coumarin derivatives is also useful due to better yield and shorter reaction time compared with the classical procedures (entry 10).
6,8-Diiodocoumarin derivatives have also been synthesized in good yields by Knoevenagel condensation using piperidine as catalyst (entry 11). The reaction of 3-ethoxysalicylaldehyde with ethyl acetoacetate in the presence of piperidine leads to 3-acetyl-8-ethoxycoumarin (entry 12).
2.3 Baylis-Hillman reaction
Baylis-Hillman strategy has been employed to the synthesis of substituted coumarins as shown in Figure 14. When 2-hydroxybenzaldehydes 18 are subjected to react with methyl acrylate 39a (R2 = Me) in the presence of DABCO (1,4-Diazabicyclo[2.2.2]octane), a mixture of chromenes 40 and coumarins 41 are formed [101, 102]. However, similar reactions of 2-hydroxybenzaldehydes 18 with tert-butyl acrylate 39b (R2 = tBu) under classical method [103] and/or microwave irradiation [104] afford corresponding Baylis-Hillman adducts 42, which undergo cyclization under reflux in AcOH yielding a mixture of 3-substituted chromene 43 and coumarin 44. Treatment of the Baylis-Hillman adducts 42 with concentrated HCl in refluxing AcOH produces 3-(chloromethyl) coumarins 45 in excellent yields. Moreover, the reaction of 42 with HI under reflux in a mixture of Ac2O and AcOH furnishes 3-methyl coumarins 46, which upon further reaction with SeO2 affords the corresponding 3-formyl coumarins 47.
Figure 14.
Synthesis of 3-substituted coumarins.
The suggested mechanism for the formation of the coumarin derivatives 44/45/46 is shown in Figure 15.
Figure 15.
Possible mechanism for the formation of 3-substituted coumarins.
Kaye et al. have also demonstrated the synthesis of substituted coumarins employing Baylis-Hillman strategy in different ways as shown in Figure 16 [105, 106].
Figure 16.
Synthesis of 3-substituted coumarins.
2.4 Kostanecki reaction
4-Arylcoumarins 59 have been synthesized in good yields employing Kostanecki reaction between 2-hydroxybenzophenones 57 and acetic anhydride 58 in the presence of DBU under mild condition (Figure 17) [107].
Figure 17.
Synthesis of 4-arylcoumarins.
The mechanism of the Kostanecki reaction is outlined in Figure 18.
Figure 18.
Mechanism for Kostanecki reaction.
Similarly, 3,4-disubstituted coumarins 65 are isolated from readily available 2-acyloxybenzophenones 64 under Kostanecki reaction conditions (Figure 19) [107].
Figure 19.
Synthesis of 3,4-disubstituted coumarins.
2.5 Michael addition reaction
Michael addition could be applied [108] to the synthesis of 3-aroylcoumarins 68 in good yields from easily available 2-hydroxybenzaldehydes 66 and α-aroylketene dithioacetals (AKDTAs) 67 in the presence of a catalytic amount of piperidine in refluxing THF (Figure 20).
Figure 20.
Synthesis of 3-aroylcoumarins.
The reaction proceeds via initial Michael addition followed by intramolecular aldol condensation reaction as depicted in Figure 21.
Figure 21.
Probable mechanism for the formation of 3-aroylcoumarins.
2.6 Wittig reaction
Kumar and coworkers [109] have reported the synthesis of substituted coumarins 3 from phenolic compounds 23 containing ortho-carbonyl group and triphenyl (α-carboxymethylene)phosphorane imidazole ylide 73 via intramolecular Wittig cyclization in good yields (Figure 22). All the reactions proceed via formation of the phosphorane intermediates 74 as established by spectroscopic results.
A series of 4-carboxy(ethyl/methyl) coumarins 76 have been synthesized in good yields from substituted phenols 1 and di(ethyl/methyl)acetylene-dicarboxylate 75 in the presence of phosphinite ionic liquid (IL-OPPh2) under solvent-free microwave irradiation conditions (Figure 23) [110]. It is noticed that the diphenylphosphine group in ionic liquid accelerates the reaction.
Figure 23.
Synthesis of 4-carboxy(ethyl/methyl) coumarins.
The proposed mechanism for the formation of coumarins 76 via vinyl phosphonium salt-mediated electrophilic substitution is shown in Figure 24.
Figure 24.
Proposed mechanism for the synthesis of substituted coumarins via vinyl phosphonium salt-mediated electrophilic substitution.
4-Carboxymethyl coumarins 82 have been synthesized by Yavari et al. [111] in moderate to excellent yields from the reactions of substituted phenols 1 and dimethyl acetylenedicarboxylate (DMAD) 81 in the presence of triphenylphosphine (Figure 25) via vinyl triphenylphosphonium salt-mediated aromatic electrophilic substitution reaction as mentioned in Figure 24. Similar results are found from the given starting materials under microwave irradiation in shorter reaction time [112].
Figure 25.
Synthesis of 4-carboxymethyl coumarins.
However, reactions of di- and trihydric phenols with dimethyl acetylenedicarboxylate (DMAD) in the presence of triphenylphosphine in toluene under reflux afford polyfunctionalized coumarin analogues along with unwanted by-products in appreciable amount (Figure 26) [113].
Figure 26.
Synthesis of polyfunctionalized coumarin analogues.
Similar reactions of 2-hydroxybenzaldehydes 18 with di(ethyl/methyl)acetylenedicarboxylates 75 leads to the corresponding 4-carboxy(ethyl/methyl)-8-formyl coumarins 93 in moderate to good yields (Figure 27) [114].
Figure 27.
Synthesis of 4-carboxy(ethyl/methyl)-8-formyl coumarins.
The methodology has also been employed to the synthesis of angular pyridocoumarins 97/98 and benzo-fused 6-azacoumarin 100 as shown in Figure 28 [115].
Figure 28.
Synthesis of pyridocoumarins and benzo-fused azacoumarin.
2.8 Palladium-catalyzed reactions
Palladium-catalyzed reactions between substituted phenols 101 and ethyl propiolates 102 lead to substituted coumarins 103/104 (Figure 29) [116, 117].
Figure 29.
Synthesis of substituted coumarins.
Unsymmetrical monohydric phenols having m-OMe or m-Me substituent as respectively in 3-methoxyphenol and m-cresol show regioselectivity toward the formation of a new bond in coumarins, which occurs at the para position to the methoxy group, and therefore, the regioisomers 103 are found to be formed predominantly over 104. However, symmetrical dihydric phenol with OMe substituent like that in 5-methoxybenzene-1,3-diol affords the regioisomer 104 predominantly over 103 under the reaction condition applied. This may be due to the steric effects of the R4 group of ethyl propiolate 102, which dominates over the electronic effect of the methoxy group of the phenol.
A proposed mechanism for the formation of coumarins 103/104 is shown in Figure 30.
Figure 30.
Possible mechanism for Pd-catalyzed synthesis of coumarins.
Substituted coumarins 3 have been synthesized in moderate yields (42–69%) via Pd(OAc)2-catalyzed reaction of substituted phenols 1 with substituted propiolic acid 110 (R3 = CO2H) in TFA under mild conditions (Figure 31, Condition A) [118]. However, a mixture of catalysts FeCl3 and AgOTf showed better catalytic efficiency toward yields (60–93%) of coumarin derivatives 3 (Figure 31, Condition B). Propiolic acid ester 110 (R3 = CO2Et) also furnishes the desired products 3 upon reactions with substituted phenols 1 under specified conditions as provided in Figure 31 (Conditions C and D) [119, 120, 121].
Figure 31.
Synthesis of substituted coumarins.
4,6-Disubstituted coumarins 113 have been achieved employing palladium-catalyzed tandem Heck-lactonization of the Z- or E-enoates 112 with o-iodophenols 111 (Figure 32, Conditions A, B, and C) [122, 123].
Figure 32.
Synthesis of 4,6-disubstituted coumarins.
For Heck-lactonization, the enoate Z-112a is found to be more reactive than its E-isomer, leading to the corresponding coumarin 113 in good yields (68–84%) under all reaction conditions studied. The enoate Z-112b leads to coumarin derivative 113 in relatively lower yields (42–56%), which may be due to the presence of the bulky tBu ester group that hampers the lactonization step. Moreover, the reactivity of E-enoates depends on the β-substituent. E-enoates 112c (R2 = CH2CHMe2, R3 = CH3) and 112d (R2 = R3 = CH3) having CH2CHMe2 and CH3 group, respectively, at the β-carbon, and their double bonds are therefore less sterically hindered than that in E-enoate 112a. This reduced hindering is a major factor for the higher reactivity of E-enoates 112c and 112d than E-enoate 112a.
Palladium-catalyzed carbonylative annulation of terminal alkynes 110 (R2 = H; R3 = nPr, Ph, SiMe3, SiEt3, CO2Et, etc.) with o-iodophenols 111 affords 3-substituted coumarins 114 (R2 = H) in poor yields (18–36%) (Figure 33) [124]. On the other hand, both 3- and 4-substituted coumarins 114 (R2 = H) and 115 (R2 = H) have been synthesized from o-iodophenols 111 and terminal alkynes 110 (R2 = H; R3 = nC4H9, nC8H17) bearing long alkyl chain. In addition, a wide variety of 3,4-disubstituted coumarins 114/115 (R2, R3 ≠ H) have also been achieved in moderate to good yields (43–78%) via carbonylative annulation between o-iodophenols 111 and internal alkynes 110 (R2, R3 ≠ H) [125].
Figure 33.
Synthesis of 3, and 4-substituted and 3,4-disubstituted coumarins.
The suggested mechanism of the carbonylative annulation is presented in Figure 34. The carbonylative annulation process is believed to proceed via (a) oxidative addition of o-iodophenol 111 to Pd(0), (b) insertion of alkyne 110 into the aryl-palladium complex 116, (c) CO insertion into the resulting vinylic palladium species 118, and (d) nucleophilic attack of the phenolic oxygen on the carbonyl carbon of the acylpalladium complex 119 with simultaneous regeneration of the Pd(0) catalyst.
Figure 34.
Possible mechanism for the synthesis of coumarins via carbonylative annulation.
3,4-Disubstituted coumarins 121 are also isolated in good to excellent yields from readily available 2-(1-hydroxyprop-2-ynyl)phenols 120 via palladium-catalyzed dicarbonylation process in the presence of KI in MeOH at room temperature (Figure 35) [126].
Figure 35.
Synthesis of 3,4-disubstituted coumarins.
Furthermore, electrophilic palladium-catalyzed cycloisomerization of brominated arylpropiolates 122 followed by Suzuki coupling with arylboronic acids furnishes 4-arylcoumarins 123 in moderate to good yields (Figure 36) [127]. This strongly suggests that a single loading of catalyst Pd(OAc)2 could be used to conduct sequential reactions for the synthesis of substituted coumarins.
Figure 36.
Synthesis of 4-arylcoumarins.
2.9 Other methods
CuOAc-catalyzed hydroarylation of methyl phenylpropiolates 124 having a methoxy methyl (MOM)-protected hydroxyl group at the ortho-position with various arylboronic acids followed by acidic workup leads to 4-arylcoumarins 59 in good to excellent yields (Figure 37) [128].
Figure 37.
Synthesis of 4-arylcoumarins.
Substituted coumarins 126 are obtained in moderate to excellent yields by Yb(OTf)3-catalyzed reactions of substituted phenols 1 with alkylidene Meldrum’s acid 125 in CH3NO2 at 100°C (Figure 38) [129].
Figure 38.
Synthesis of substituted coumarins.
A series of 3-alkylcoumarins 128 are obtained in moderate yields from 2-hydroxybenzaldehydes 18 and α,β-unsaturated aldehydes 127 via generation of N-heterocyclic carbenes (NHC) in ionic liquid under conventional heating (Figure 39, Condition A) and/or microwave irradiation conditions (Figure 39, Condition B) [130].
Figure 39.
Synthesis of 3-alkylcoumarins.
3-Benzoylcoumarins 130/131 and coumarin-3-carbaldehydes 47 have also been isolated in moderate to good yields from the reactions of 2-hydroxybenzaldehydes 18/19 with phenylpropionyl chloride 129a and/or propionyl chloride 129b under esterification conditions (Figure 40) [131].
Figure 40.
Synthesis of 3-benzoyl coumarins and coumarin-3-carbaldehyde.
An electrochemical method has been developed for the synthesis of 6H-benzo[c]chromen-6-ones 133 in good to excellent yields from biphenyl-2-carboxylic acids 132 via radical arene carbon–oxygen bond formation reaction (Figure 41) [132]. The method involves DDQ as a redox mediator, inexpensive glassy carbon electrodes to facilitate an intramolecular lactonization of biphenyl-2-carboxylic acid derivatives, and 2,6-lutidine as an additive, in 0.1 M nBu4NClO4 electrolyte mixture of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP).
Figure 41.
Synthesis of 6H-benzo[c]chromen-6-ones.
3. Concluding remarks
In this chapter, we have discussed a plethora of methods for the one-pot synthesis of coumarin derivatives and their advantages and/or demerits compared to other methods. Both the Pechmann as well as Knoevenagel condensation reactions under microwave and/or ultrasound irradiation conditions, and catalyzed by ionic liquids and/or solid acids have several advantages including high products yields, diminutive reaction times, ease of isolation of products, recycle of catalysts, and green aspects by avoiding toxic catalysts and solvents. Chemo- and regioselective syntheses of 3-substituted coumarins have been reported via Baylis-Hillman reactions under mild conditions. On the other hand, vinyl phosphonium salt-mediated electrophilic substitution reactions of phenols afford 4-carboxyalkyl coumarin derivatives in good yields under neutral conditions. This method offers significant advantages for the synthesis of coumarins having acid sensitive functional groups. In contrast, the most widely used method von Pechmann condensation requires acidic conditions. Moreover, palladium-catalyzed Heck lactonization protocol has been employed for the regioselective synthesis of coumarin derivatives from o-iodophenols and enoates. It is revealed that this reaction is sensitive to steric hindrance around the double bound in the enoates. Regioselective synthesis of 3,4-disubstituted coumarins achieved from substituted 2-iodophenols and alkynes containing different substituents via palladium-catalyzed carbonylative annulative process is sensitive to the steric bulk of the alkynes, and alkynes bearing tertiary alkyl substituents generally fail to undergo annulation. Unsymmetrical alkynes produce mixtures of regioisomers with generally only modest selectivity. Kostanecki reaction protocol furnishes a notable improvement in reaction conditions for coumarin synthesis and gives rise to the advantage of its synthetic capability, especially for highly functionalized 4-arylcoumarins with structural diversity.
Acknowledgments
Dr. I. Ansary and Dr. A. Taher highly acknowledge the Department of Chemistry (Burdwan University) and Burdwan Raj College, respectively, for infrastructural facilities.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"coumarin derivatives, one-pot synthesis, methods and procedures, advantages and disadvantages",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/69675.pdf",chapterXML:"https://mts.intechopen.com/source/xml/69675.xml",downloadPdfUrl:"/chapter/pdf-download/69675",previewPdfUrl:"/chapter/pdf-preview/69675",totalDownloads:1170,totalViews:0,totalCrossrefCites:2,totalDimensionsCites:4,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:59,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"January 31st 2019",dateReviewed:"August 4th 2019",datePrePublished:"October 22nd 2019",datePublished:"February 12th 2020",dateFinished:"October 22nd 2019",readingETA:"0",abstract:"Coumarin derivatives have a myriad of applications in medical science, biomedical research, and many industrial branches. For this reason, many efforts are being dedicated to the development of novel and more practical methods for synthesizing these compounds. This chapter describes several methods of one-pot synthesis of coumarin derivatives, including von Pechmann condensation, Knoevenagel condensation, Baylis-Hillman reaction, Michael addition, Kostanecki reaction, vinyl phosphonium salt-mediated electrophilic reaction, and Heck-lactonization reaction. The methods are compared with each other, and the advantages and disadvantages of each of them are addressed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/69675",risUrl:"/chapter/ris/69675",book:{id:"8077",slug:"phytochemicals-in-human-health"},signatures:"Inul Ansary and Abu Taher",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Methods to synthesize coumarin derivatives",level:"1"},{id:"sec_2_2",title:"2.1 Pechmann condensation reaction",level:"2"},{id:"sec_3_2",title:"2.2 Knoevenagel condensation reaction",level:"2"},{id:"sec_4_2",title:"2.3 Baylis-Hillman reaction",level:"2"},{id:"sec_5_2",title:"2.4 Kostanecki reaction",level:"2"},{id:"sec_6_2",title:"2.5 Michael addition reaction",level:"2"},{id:"sec_7_2",title:"2.6 Wittig reaction",level:"2"},{id:"sec_8_2",title:"2.7 Vinyl phosphonium salt-mediated electrophilic substitution reaction",level:"2"},{id:"sec_9_2",title:"2.8 Palladium-catalyzed reactions",level:"2"},{id:"sec_10_2",title:"2.9 Other methods",level:"2"},{id:"sec_12",title:"3. Concluding remarks",level:"1"},{id:"sec_13",title:"Acknowledgments",level:"1"},{id:"sec_16",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Kumar S, Saini A, Sandhu JS. LiBr-mediated, solvent free von Pechmann reaction: Facile and efficient method for the synthesis of 2H-chromen-2-ones. 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Department of Chemistry, The University of Burdwan, India
Department of Chemistry, Bankura University, India
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1. Introduction
In the wake of the Notre Dame Cathedral fire, digital scans collected by Dr. Andrew Tallon [1] offer the hope for future restoration. One question raised is, what Level of Geometric Accuracy (LOGA) can the reconstructed digital replica achieve with respect to the physical asset? In the Architecture, Engineering and Construction (AEC) sector, operation and maintenance (O&M) costs can range between 60 and 80% of total life cycle costs, which is three times greater than the cost of design and construction [2]. This demonstrates the significance of implementing intelligent asset documentation and structural health monitoring (SHM) approaches for existing built assets. Laser scanning has been widely used to document and monitor existing conditions of real-world assets in the form of point clouds [3, 4]. A point cloud is an unstructured low-level digital representation, which by itself does not contain any meaningful information of the documented asset. A ‘twinning’ process is utilised to convert the low-level data into a high-level digital representation in a structured format, namely, a geometric Digital Twin (gDT) [5]. The gDT can be further enriched with other information, such as semantic meanings, texture, materials, damage, energy use, maintenance data and so forth from its physical twin using IoT technologies [6], to form an information enriched model over time, namely, a ‘digital twin’ (DT). ‘Geometric accuracy’ is a vital indicator that guides and describes the degree of spatial accuracy of the resulting twin. It is conventionally deemed as the Represented Accuracy [7] that denotes the standard deviation range to be achieved once the point cloud is twinned into a geometric model. Twinning a real-world asset is an interpretive process, where geometric accuracy largely depends on a modeller’s experience and discretion [5]. While in their unstructured state, point clouds contain more geometric details than a resulting gDT created from the point cloud. Therefore, the resulting ‘best-fit’ gDTs are highly unlikely to be as accurate as the measured data (e.g., a point cloud) at the end of the twinning process [8]. This is also true for the automated methods since there is a trade-off between the achieved geometric accuracy and the quantity of information used for describing existing constructive objects in arbitrary shapes [9]. This occurs because the process of twinning involves simplifications to create polygon- or mesh-based primitives so that it ‘smooths’ discontinuities and gaps in point clouds [10]. This means that almost every object is approximated in order to transform point-cloud-based descriptors (in non-parametric formats) into parametric primitives [11]. Figure 1 illustrates a series of components for a bridge asset where the point cloud is converted into bespoke gDT elements. However, since point clouds often contain defects, such as varying point density [12] and occlusions [13], it is difficult or often not feasible to achieve a desired LOGA for resulting gDTs [5]. When these conditions occur, what are realistic expectations for a modeller or of an automated method with regard to representing the reality and meeting the required accuracies for SHM?
Figure 1.
Customising shapes of bridge components and fitting them to point clusters.
Numerous specifications termed as LOX (e.g. Level of Development and Level of Detail) have been developed to guide practitioners and researchers when creating digital models [14]. What do the LOX mean? How to measure whether the specifications were met? What is the best practice approach to reflect when the employer requires ‘1 cm accuracy’ or ‘every element to be within a half centimetre’? This chapter explores these questions, aiming (1) to provide a critical review of existing specifications and twinning implementations, (2) to identify technical twinning challenges, and (3) to inform the establishment of a geometric-accuracy-based evaluation system for twinning and updating.
2. Background
2.1 Existing LOX
The term ‘LOD’ was initially introduced by Vico Software [15]. Ambiguity of defining LOD stems largely from the fact that the American Institute of Architects (AIA) later adopted this concept and kept the acronym LOD but changed it to mean ‘Level of Development’ rather than ‘Level of Detail’ [16]. It was then superseded by the document AIA G202™ [17], which defines five progressively detailed levels of completeness: LOD100–LOD500. Based on the AIA protocols, the BIMForum [18] released another LOD specification, which was identical to those published in the AIA’s Digital Practice Documents [19], but with two exceptions. First, a new LOD was designated as LOD350. Second, the LOD500 was removed from the specification. The geometric requirements of gDT elements of LOD300, LOD350, and LOD400 are defined in the same way in terms of accuracy. However, this BIMForum document does not elaborate on what is implied by ‘accurate’ or how to measure it. Bolpagni [20, 21, 22] summarised the history of the LOX classification system in Table 1. Various new classification systems have been developed to accompany and complement the BIMForum’s LOD specification. For example, New Zealand proposed a LOD specification that contains five maturity levels [23], each of which is a sum of different aspects that define the geometry and information of gDT elements. Among these, Level of Detail (LOD) and Level of Accuracy (LOA) do not specify any quantitative standards. Royal Institution of Chartered Surveyors [24] proposed a concept of building survey detail accuracy banding, which defines accuracies to be achieved for different surveyed features when an employer requires a customised geometric accuracy and confidence level. This banding, however, is tailored for designing building settings consisting of cuboids defined by length, width, and height. Similarly, Abualdenien and Borrmann [25] introduced a multi-LOD meta scheme, taking into account the geometric uncertainties by assigning quantitative fuzziness in cm. Again, the usefulness of this scheme in describing the twinning quality is unknown. To this end, Banfi [26] and Banfi et al. [27] proposed a new Grades of Generation (GoG) protocol for twinning highly complex historic structures from point clouds. LOGA was defined as the error resulting between the reconstructed objects and the point clouds using metrics such as the mean distance, median distance, and standard deviation. The USIBD specifications [7] were the first to provide the means to report twinning results of existing building conditions (from point clouds) based on standard deviation (stdev). It articulates the ‘accuracy’ as well as the five different LOAs (Figure 2) by which to represent real-world out-of-plumb geometries. Specifically, the Measured Accuracy represents the stdev range that is to be achieved to acquire a point cloud, regardless of the method used. In contrast, the Represented Accuracy represents the stdev range that is to be achieved when a point cloud is twinned. This guideline, however, does not indicate how to achieve and how to measure the Measured Accuracy and Represented Accuracy. As shown, various acronyms are used across countries and organisations. These acronyms are either identical or interchangeable, making them very challenging to be understood or adopted.
Country/region
Document
Year
LOX
Whole gDT
gDT element
Geometric data/info
Non-geometric data/info
Denmark
BIPS
2007
Information Level
√
√
√
√
Australia
CRC
2009
Object Data Levels/Level of Detail
√
√
√
USA
Department of VA
2010
Level of Development
√
√
√
USA
Vico Software
2011
Level of Detail
√
√
√
√
Australia
NATSPEC
2011
Level of Development
√
√
√
Hong Kong
HKIBIM
2011
Level of Detail
√
√
√
USA
NYC DDC
2012
Model Level of Development/Level of Development
√
√
√
√
Model Granularity
√
√
√
Penn State University
2012
Level of Development
√
√
√
USC
2012
Level of Detail
√
√
US Army Corps of Engineers (USACE)
2012
Level of Development
√
√
√
Singapore
BCA
2013
Level of Detail
√
√
√
UK
PAS 1192–2
2013
Level of Model Definition
√
√
√
Level of Model Detail
√
√
Level of Model Information
√
√
UK
CIC BIM Protocol
2013
Level of Detail
√
—
—
—
Germany
BMVBS
2013
Level of Development
√
√
√
Netherland
BIM
2014
Information Level
√
√
√
√
Canada
AEC
2014
Level of Development
√
√
France
Le Moniteur
2014
Level of Detail/Level of Development
√
√
√
Australia
BCPP
2014
Level of Development
√
√
√
Level of Detail
√
√
Level of Accuracy
√
√
√
Level of Information
√
√
Level of Coordination
—
—
—
—
China
CBC
2014
Level of Detail
√
√
√
√
Belgium
ABEB-VBA
2015
Level of Development
√
√
√
Germany
D&R
2015
Level of Development
√
√
USA
BIMForum
2015
Level of Development
√
√
√
Element Geometry
√
√
Associated Attribute Information
√
√
UK
NBS BIM Toolkit
2015
Level of Detail
√
√
Level of Information
√
√
UK
AEC (UK)
2015
Level of Definition Level of Information Grade/Level of Detail
√
√
√
√
√
√
√
China
SZGWS (Shenzhen)
2015
LOD
√
√
√
Table 1.
Comparison of the LOX classification system across countries.
Figure 2.
Measured and represented accuracy [7].
2.2 Industry applications
Leading software vendors provide advanced commercial twinning solutions, which are currently semi-automated processes at best. ClearEdge3D Edgewise software can automatically extract geometric features for industrial constructive elements and basic architectural elements using cross-sections in user-cropped regions followed by fitting 3D shapes from a library of preloaded features [28, 29]. This means, the current practice can achieve a high degree of automation of twinning if the resulting geometries are assumed to be generic or pre-defined. However, in the context of SHM, this assumption is unrealistic if a millimetre twinning accuracy is required. Twinning arbitrary geometries using point clouds is quite challenging [30]. Most authoring tools are designed to model orthogonally, or along local coordinate axes. They employ the use of rigid-body parameters to design construction elements by defining cross-sectional shapes, length, width and height parameters, whereas in the real world, as-is components are often warped, off-plumb, or contain deflections [31]. While finite element analysis and multi-physics engines can be used to predict elastic and plastic distortions in materials [32], current digitization workflows that produce parametric objects cannot capture distortion such as bowing in a beam or welding distortion in steel frames. Errors are introduced when the as-is geometries are twinned as being plumb and subjected to rigid-body physics [33]. In this case, geometry deviation analysis is important because unfitted geometries would potentially reduce the reliability of the gDT to be used for structural analysis and defect detection for SHM purposes. Current authoring applications are not capable of carrying out geometry deviation analysis for point clouds. The actual geometry deviation analysis requires third-party middleware software to interpret and investigate. FARO BuildIT Construction [34] is the most recent verification software for dimensional quality control (QC) process. Measured data collected from laser scanners can be compared against a gDT to analyse geometric deviations (Figure 3). However, it is worth noting that the nature and origin of a deviation is not identified in the analysis directly. Specifically, the analysis itself is often in the form of a ‘heat map’, where deviations are plotted in colours that correspond to a specific magnitude and direction from a perfect state (i.e. 0 mm deviation). However, point clouds contain voids and sparse measurements, which as directly classified deviations. These false positive measurements make it difficult to interpret the deviation analysis results. Users must manually inspect datasets to observe and detect gross errors or missing components. Currently, there are no available automated solutions for this in existing middleware. In addition, once deviations are identified through deviation analysis and manual interpretation, users must also manually apply changes to update the authoring gDTs. This is currently a large challenge since there is very little research into automated updating of gDT from point clouds [35, 36].
Figure 3.
Deviation analysis of a pipe assembly (point cloud data courtesy of FARO Technologies, Inc.).
2.3 Existing research methods
Automated methods have been proposed to streamline the twinning process (Table 2) [37, 38]. However, user intervention was still required for some crucial steps [44]. Zhang et al. [40] and Laefer and Truong-Hong [47] produced gDTs for bridges and industry plants, but without a geometric deviation assessment. Anil et al. [39] were among the pioneers who discussed in depth the problem of geometric deviation. They suggested using minimum Euclidean distance and thresholding [49] as metrics to evaluate the fitting quality (CAD model against point clouds). The deviation analysis at macro level (for the whole structure) was performed using a commercial software application (i.e. Polyworks v9). Bonduel et al. [46] suggested assessing the twinning results at both macro and micro levels. They used CloudCompare to analyse the deviations between a point cloud and a manually generated building floor gDT. They also discussed the achieved represented accuracy using LOAs provided by USIBD. Then, Hausdorff distance was proposed to measure the fitting deviation of a mesh-based building gDT reconstructed from a synthetic point cloud [41]. Thomson and Boehm [42] suggested using Euclidean distance and area difference based on the width and length, and angular difference to measure the fitting quality of walls. Although these measurements can assess elementwise quality, they are tailored for generic building walls in cuboid shapes. Similarly, Valero et al. [43] assessed fitting deviations of individual furniture objects and walls using orientation, dimension, positioning, and sizing metrics, assuming these objects consist of planar surfaces. Lu et al. [5] proposed an automated fitting method to twin bridge components. They gauged the fitting accuracy using Cloud-to-Cloud (C2C) distance metrics—a similar metric used by Shirowzhan et al. [51]. However, the geometric deviation evaluation was performed only at the macro level. NURBS-based methods [27, 44, 45, 48] were employed to reconstruct geometric surfaces for building, industry plant, and historic building elements. Note that the generation of compound pipes requires user intervention to group a set of cylindrical segments followed by automatically fitting surfaces [44]. Likewise, highly complex historic structures require manual surface generation, although extremely high twinning accuracy was reported [27]. Point-to-surface distance metrics were used to evaluate the fitting quality [44, 48]. In contrast, Barazzetti [45] used the commercial package Geomagic Studio to evaluate the fitting accuracy of the NURBS curves through a progressive densification (i.e. multi-resolution) approach. As shown, there is no fully automatic method to produce geometrically highly accurate twins for existing assets. Also, more comprehensive evaluation metrics need to be established for assessing twinning quality.
Point cloud authenticity real (R) or synthetic (S)
Previous sections have discussed that twinning existing assets using point clouds is restricted by current software tools which are limited in their ability to represent out-of-plumb conditions and non-rigid formations. It is also restricted by the limits of the data itself. This section discusses this problem in detail through a case study.
Laser scanning can sample an object’s surface as it exists with highly accurate spatial measurements in the form of 3D points. If the documented object is not straight or plumb, the scanner can capture its geometric status. Theoretically, a terrestrial laser scanner such as the FARO Focus 3D X330 [52] has a ranging error of ±2 mm at 10 m, equating to a systematic measurement error at around of 1σ at 10 m. However, the measured accuracy is affected by many factors, including the standard deviation of the sensor, registration methods, material type being scanned, low temperature, bad weather, and strong sunlight [53]. The overall twinning error ET can be expressed as a combination of three primary sources of error:
ET=ERA+EM+ER,E1
where ERA is the ranging error associated with the laser scanner, EM is the measured error introduced during scanning and registration, and ER is the represented error resulting from the process of scan-to-gDT. It is important to specify the error associated with each source independent of each other since they are assumed to be mutually exclusive. In this chapter, we only focus on discussing the represented error ER, which is independent of the sensor, or parameters of the documented object, or scanning and registration methods. It is related to the manner with which the measured point cloud is being transformed into the outcome, i.e. a gDT and describes the extent the gDT matches the acquired points.
As mentioned earlier, existing authoring software packages are by nature orthographic modelling tools. The challenge with using these software packages becomes how to represent a structure’s up-to-date conditions. To complicate matters further, the as-weathered, as-damaged, or as-deviated information of existing assets further increases the representation difficulty. Fitting deviations will be generated and propagated if these conditions are represented in an over-simplified fashion. In addition, sparseness, hidden, or concealed conditions are often encountered in point clouds, making it difficult or impossible to twin constructive objects with certainty. Thus, ER is the accumulated error from the geometric deviations and the propagation of data uncertainty.
Figure 4 demonstrates current efforts on parametric bridge design [54]. The essential feature for bridges is the horizontal and vertical alignments, which control the parametric relationships and dependencies between assembly systems and all components. The deck cross-sections are then driven by the bridge alignment curves. They are profiles that are used in conjunction with the alignment to derive the overall 3D shape of the bridge deck.
Figure 4.
Parametric cross section design of a slab-beam bridge with user-defined geometric constraints [54].
When SHM and retrofit planning is being performed, accurate as-is condition data is required regardless of the availability of the as-designed parametric information. Point clouds can depict the as-is geometries of an asset using thousands of data points. However, maintaining the dimensional accuracy and geometric fidelity of a given bridge point cloud is challenging because the usefulness of topological and geometric constraints is limited to very simple geometric shapes and spatial relationships. As-is geometries do not exhibit a parametric pattern with respect to the initial primitives used to create the as-designed model. Figure 5 illustrates the non-orthogonal geometries of a real-world bridge point cloud cannot be fitted using generic shapes, such as cuboids, in an orthogonal fashion. The modelled slabs do not follow the point cloud and produce fitting deviations when they are joined at sharp angles (Figure 5a). These deviations become smaller if the cross-sections are outlined with as-is 2D shapes. However, the bridge gDT does not necessarily close better and become manifold as the fitting quality is improved at the expense of broken or clashing connections (Figure 5b). This is especially true when twinning point clouds of pipes with sags, beams and columns with welding distortion or walls that are skewed. Adjacent components do not fit to properly watertight connections unless they are joined at right angles. For example, Figure 6 illustrates part of a piping system generated using point clouds. The local deviation is reduced from 30 to 1 mm when watertight connections are not used. Given the challenge with the mediation of non-parametric real-world deviations to parametric model primitives, modellers are often forced to leave objects ‘slightly off-axis’ or perform ‘unnatural shape editing’ by eliminating or ignoring as many overlapping and joint warnings as possible in order to match the points.
Figure 5.
Fitting geometric shapes to bridge point clouds. (a) Point clouds fitted by cuboids; (b) point clouds fitted by best-fit shapes.
Figure 6.
Fitting cylinders to piping point clouds (point cloud data courtesy of FARO Technologies, Inc.).
When facing occlusions and damage conditions, the geometric accuracy has a reliance on human perception followed by inferring the hidden information based on assumptions. For example, a bearing plays an important role in a bridge, but its surface is less than 1% of that of the deck slab and has a complex composition. These characteristics make it difficult to be fully captured by a laser sensor (Figure 7a). In addition, point clouds need to be down sampled before feeding into in-memory-system-based authoring tools or automated algorithms that cannot handle huge datasets. The down sampling is often performed using a third-party processing software application, which applies generic filters to evenly down sample the points without considering local geometric context. While this is certainly helpful and creates beneficial data compression, the resulting datasets often lose information along the way (i.e. sparse areas or smaller objects will have little to measurements). Thus, only a few points are retained for the bearing surface which does not provide enough information to support the twinning task and result in geometry uncertainties (Figure 7b). The interpretation of bearing shapes largely depends on modeller’s knowledge and discretion, which could introduce connection problems (e.g., clashing/gaps) (Figure 7c). Uncertainty increases when working with point clouds containing skewness and noise (Figure 7d and e). Although methods have been suggested to work under occlusions and sparseness [5, 55], the certainty of the resulting models is rarely investigated.
Figure 7.
Bearing gDT generation under uncertainty. (a) Original point cloud; (b) down-sampled point cloud; (c) bearing shapes and connection problem; (d) (e) geometry uncertainty in point clouds.
Figure 8 shows an example of a bridge where little-to-no measurements were captured in the girder areas due to a limited line of sight [56]. Like many existing works, both the manual and the automated method inferred specific girder profiles and produced gDTs with detailed dimensions using engineering knowledge. Then, Cloud-to-Cloud (C2C) distance could be used [5] to compute the deviation between the point clouds sampled from the manually generated gDTs (Manual) and the automated ones (Auto), and the real point clouds (Real):
Figure 8.
Geometric deviation with complete girder profiles in occluded areas.
C2C=maxdist¯Manual or Auto/Realdist¯Real/Manual or Auto,E2
where dist¯ is the estimated distance between a compared point cloud (i.e. Manual or Auto) and a reference point cloud (i.e. Real). Non-trivial fitting deviations occurred and raised the overall macro-level deviation (C2CAuto—12.5 cm and C2CManual—5.7 cm) [5]. These significant fitting deviations were due to the occluded areas, as no measurements were available to compare against, resulting in an incorrect gDT from a geometric accuracy standpoint. This solution is straightforward since it does not take the modelling uncertainties into account. It simply takes uncertain areas as errors. Figure 9 illustrates that the fitting deviation was drastically reduced by approximately 70% (C2CAuto—4.2 cm) if we replace the complete girder profiles with unclosed mesh-based gDTs while other parts remain unchanged. Yet still, the improved accuracy only aligns with USIBD’s LOA 20 (lower range: 15 mm, and upper range: 5 cm, at 2σ) [7], corresponding to a relatively low accuracy standard. USIBD provides different represented accuracy levels, but it does not specify how to measure it. For example, we can only use a couple of reference points to estimate the accuracy. It is the averaged fraction between pair reference-point distances in the registered scan data and the corresponding pair on-site or gDT point distances:
Figure 9.
Geometric deviation with incomplete girder profiles in occluded areas.
where M is the number of investigated pair-wise distance. Then, it is possible to acquire acc¯ that aligns with a higher LOA in USIBD. By contrast, unlike acc¯, C2C is an estimation using thousands of calculated points. Therefore, the resulting C2C-based accuracy is almost surely not going to achieve an expected ‘high accuracy’ level (e.g., ±10 mm or USIBD’s LOA 30 onwards). The C2C comparison between the Auto and Real revealed that points sampled from bottom flanges of girders were well matched with the original points while the mismatched points were mainly from the central part of the deck slab where points were not evenly distributed. This is attributed to the undulating-surfaces of the gDT generated using the proposed ConcaveHull alpha-shape algorithm (Figure 9). Local indentations or bumps are generated when alpha value is too small to smooth out the surface affected by unavoidable noise, raising the fitting deviations. However, optimising the alpha value is difficult because an indentation, for instance, could be due to a defect or a hole but could also due to localised sparse and unevenly distributed points. In addition, although the ConcaveHull alpha-shape algorithm can describe slab geometries in a 2D space, it oversimplifies a 3D space.
4. Prospective twinning methods and deviation analysis
The analysis provided in the previous section demonstrates that real-world conditions are seldom orthogonal and perfect, rendering it extremely difficult to perform high-fidelity twinning with a geometric accuracy on the millimetre scale. Commonly used representation models include but are not limited to: implicit representation such as mathematical formula-based methods [57], Boundary Representation such as polygon- and mesh-based methods [41], Constructive Solid Geometry [58], Swept Solid Representation [47], and NURBS representation [45, 48]. Depending on the nature of defects, the as-damaged geometries may be represented in different ways. Figure 10 illustrates the vision of the concept of an as-damaged bridge gDT implemented for the inspection work. The method proposed by Hüthwohl et al. [59] can be used to integrate superficial defects such as cracks, efflorescence, corrosion, and slight spalling [Figure 10a—(3) and (4)] to the affected element using the back-project technology [59] (Figure 10b). In contrast, major defects, such as severe spalling, cavity and pothole [Figure 10a—(1) and (2)], are significantly different in geometry compared to their surrounding healthy (i.e. good condition) surfaces. The method proposed by Lu et al. [5] can be used to represent healthy elements; however, it cannot describe the unhealthy areas precisely, due to the extrusion-based twinning nature. Finer representation, such as mesh-based and NURBS-based twinning techniques [50], can be employed to handle the geometry complexity of significant defects in a precise manner (Figure 10b). The more variable the defect, the greater the geometric twinning needs to rely on non-parametric representation such as mesh format. One promising solution to produce a gDT that takes the as-damage information into account is to first detect unhealthy areas [60], followed by twinning these unhealthy areas using finer twinning techniques based on their type and size. However, the mesh polygon resolution should not degrade the rendered presentation. This requires an intelligent a priori scheme to resample the point clouds based on the geometric complexity of a sampled surface [61, 62].
Figure 10.
Vision of the concept of an as-damaged bridge gDT applied for inspection. (a) actual damages or defects; (b) digital representations.
Construction elements with different scales may require different twinning techniques. For example, extrusions could be efficient for twinning slab segments; however, they cannot be directly applied to bearings. This means a gDT is highly likely to contain more than one data representation type in order to balance its resolution and the LOGA, which very few works have covered in depth. In addition, as previously mentioned, occlusions and sparseness increase the uncertainty of the resulting gDT. These problems require a more intuitive geometric deviation analysis system. The macro-level deviation analysis can provide an overview of the twinning quality whereas it does not reflect a detailed comparison at the component- or feature-level. Therefore, the dimensional QC system of geometric deviation analysis should consist of both macro- and micro-level analysis. The former, can be used to quickly localise uncertain areas, or areas with major deviations (Figures 8 and 9) while the latter can provide detailed deviation analysis at the component-level, indicating a more meaningful LOGA of specific elements. Table 3 shows an example of the C2C-based geometric deviation analysis of five bridge gDTs using an automated twinning method. The micro-level numerical indications show that the deck slab takes the bigger part of the overall deviation whereas the other components such as pier caps, piers, and girders take the smaller part. Specifically, for all these bridges except Bridge 7, the deviations stemming from deck slabs are 2.9, 3.2, 2.1, and 1.5 times bigger than that of the averaged value for the remaining components, respectively. Bridge 7 initially appears misleading since the slab deviations are only 48.8% of that of its girders. However, these abnormal deviations are due to significant occlusions in the raw data. The distribution of the deviations is not necessarily proportional to the LOGA. This can be demonstrated through the coverage area of components. The deck slab takes most of the sampled surface compared to that of the pier caps and piers, which are much smaller in size and in covered area. Specifically, pier caps, piers, and girders take 12, 10.4, 7.2, 31.7, and 15.6% of the overall sampled surface of each bridge, respectively. This means although the absolute twinning accuracy of smaller components is higher than larger ones, their relative accuracy is not necessarily better. A deviation analysis system that combines both macro- and micro-level information can better interpret the twinning accuracy.
Macro- and micro-level C2C geometric deviation analysis.
5. Conclusions
This chapter presents an exploratory analysis of the LOGA of geometric twinning for existing assets using point clouds. Twinning existing assets for monitoring the structural health is a daunting task since the as-is geometric conditions can differ from the designed status due to geometric anomalies, physical damages, deflections, and the complexity, ambiguities, and defects in the measured point cloud data. Section 2.1 reviews existing LOX systems that lack a clear elaboration on geometry accuracy. They share the same acronym but do not necessarily carry the same meaning. They are tailored for basic assumptions made in the design phase or at the beginning of a generative process, making them useless to interpret the as-is geometries of gDTs delivered for SHM purposes. Section 2.2 reviews on industry applications and reveals that there remains a gap between the accuracy requirements placed on gDTs and the capabilities of underlying twinning processes. Specifically, there are practical limitations of authoring tools with respect to the context of orthogonal (i.e. idealised parametric primitives) and real-world deviations (i.e. non-parametric data formats such as point clouds and meshes). Their ability to twin or capture non-rigid-body deformations is extremely limited. Likewise, limitations are also revealed for the deviation evaluation tools with respect to geometric accuracy interpretations. Despite the growing state of the art (Section 2.3), a fully automated twinning and updating process is still in its infancy. A major bottleneck for complete automation of the workflow is the definition of LOGA of the documented asset that covers all geometric deviations and data uncertainties. This requires a development of comprehensive LOGA-based evaluation metrics for gDTs generated in the post-construction stage. The case study (Section 3) demonstrates the technical challenges of the twinning process. High-fidelity twinning within millimetre-level geometric accuracy is challenging to achieve because each step introduces errors. This requires in-depth research on the level of the model certainty. LOGA is closely related to the tools, techniques, and process used to represent the specific object being documented. In the end, the twinning method and LOGA depend highly on what the gDT will be used for (Section 4), on the specific needs and goals of the project, and what kind of metadata is required when providing information about the geometric accuracy.
Parameterising point cloud data results in a loss of geometric accuracy along with a decrease of model certainty. This requires practitioners and researchers to effectively communicate the LOGA through a universal consensus before developing, evaluating, and using gDTs. Until there is a consensus and a universal system for describing geometric accuracy of gDTs, the following recommendations are provided. In the case where geometric accuracy requirements are very strict, such as in the O&M stage, it may be useful to store and link the initial as-is captured data along with the resulting gDT. The purpose for this is two-fold. First, it allows for an end-user to view the initial dataset that was used to create the gDT, for conducting its own unique accuracy or structural analysis. Storing the initial raw point cloud data will provide a level of confidence to an end-user when they use the geometric information from a gDT. It also alleviates some of the burden placed on individuals who create the gDT to provide a subjective global accuracy figure (which can have legal impacts depending on end-use of such gDTs). Secondly, linking the initial data capture avoids loss of geometric data. Since point cloud data contains much rawer geometric information than a resulting surface-based or solid-based gDT, data fidelity can be preserved. As twinning processes and algorithms continue to develop and improve (both in accuracy but also in computational efficiency) it will be possible to build, update, manage, and exploit gDTs in a progressive manner.
Acknowledgments
This research work is supported by the National Sciences and Engineering Research Council (NSERC), Mitacs and Edge Architects Ltd. and Cambridge Trimble Fund. We would like to thank them for their support. We also acknowledge Faro Technologies for their in-kind support, provision of sample point cloud data and access to BuildIT Construction software. Any opinions, findings, and conclusions or recommendations expressed in this work are those of the authors and do not necessarily reflect the views of the stakeholders who have supported this research.
\n',keywords:"digital twin, geometric accuracy, point clouds, bridge, structural health monitoring",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/72444.pdf",chapterXML:"https://mts.intechopen.com/source/xml/72444.xml",downloadPdfUrl:"/chapter/pdf-download/72444",previewPdfUrl:"/chapter/pdf-preview/72444",totalDownloads:880,totalViews:0,totalCrossrefCites:3,dateSubmitted:"October 22nd 2019",dateReviewed:"May 8th 2020",datePrePublished:"June 10th 2020",datePublished:"February 10th 2021",dateFinished:"June 10th 2020",readingETA:"0",abstract:"We present an exploratory analysis of the geometric accuracy of digital twins generated for existing infrastructure using point clouds. The Level of Geometric Accuracy is a vital specification to measure the twinning quality of the resulting twins. However, there is a lack of a clear definition of the Level of Geometric Accuracy for twins generated in the operation and maintenance stage, especially for structural health monitoring purposes. We critically review existing industry applications and twinning methods. To highlight the technical challenges with creating high-fidelity digital replicas, we present a case study of twinning a bridge using real-world point clouds. We do not provide conclusive methods or results but envisage potential twinning strategies to achieve the desired geometry accuracy. This chapter aims to inform the future development of a geometric accuracy-based evaluation system for use in twinning and updating processes. Since a major barrier for a fully automated twinning workflow is the lack of rigorous interpretation of ‘geometric accuracy’ outside design environments, it is imperative to develop comprehensive standards to guide practitioners and researchers in order to achieve model certainty. As such, this chapter also aims to educate all stakeholders in order to minimise risk when drafting contracts and exchanging digital deliverables.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/72444",risUrl:"/chapter/ris/72444",signatures:"Ruodan Lu, Chris Rausch, Marzia Bolpagni, Ioannis Brilakis and Carl T. Haas",book:{id:"10028",type:"book",title:"Structural Integrity and Failure",subtitle:null,fullTitle:"Structural Integrity and Failure",slug:"structural-integrity-and-failure",publishedDate:"February 10th 2021",bookSignature:"Resat Oyguc and Faham Tahmasebinia",coverURL:"https://cdn.intechopen.com/books/images_new/10028.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83881-981-1",printIsbn:"978-1-83881-980-4",pdfIsbn:"978-1-83881-982-8",isAvailableForWebshopOrdering:!0,editors:[{id:"239239",title:"Associate Prof.",name:"Resat",middleName:null,surname:"Oyguc",slug:"resat-oyguc",fullName:"Resat Oyguc"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"314007",title:"Dr.",name:"Ruodan",middleName:null,surname:"Lu",fullName:"Ruodan Lu",slug:"ruodan-lu",email:"r.lu@lboro.ac.uk",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"320099",title:"Mr.",name:"Chris",middleName:null,surname:"Rausch",fullName:"Chris Rausch",slug:"chris-rausch",email:"chris.rausch@uwaterloo.ca",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Waterloo",institutionURL:null,country:{name:"Canada"}}},{id:"320101",title:"Dr.",name:"Marzia",middleName:null,surname:"Bolpagni",fullName:"Marzia Bolpagni",slug:"marzia-bolpagni",email:"Marzia.Bolpagni@macegroup.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Mace (United Kingdom)",institutionURL:null,country:{name:"United Kingdom"}}},{id:"320102",title:"Dr.",name:"Ioannis",middleName:null,surname:"Brilakis",fullName:"Ioannis Brilakis",slug:"ioannis-brilakis",email:"ib340@cam.ac.uk",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Cambridge",institutionURL:null,country:{name:"United Kingdom"}}},{id:"320103",title:"Prof.",name:"Carl",middleName:"T.",surname:"Haas",fullName:"Carl Haas",slug:"carl-haas",email:"chaas@uwaterloo.ca",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Waterloo",institutionURL:null,country:{name:"Canada"}}}],sections:[{id:"sec_1",title:"1. 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School of Architecture, Building and Civil Engineering, Loughborough University, United Kingdom
Darwin College, University of Cambridge, United Kingdom
Department of Engineering, University of Cambridge, United Kingdom
'},{corresp:null,contributorFullName:"Carl T. Haas",address:null,affiliation:'
Department of Civil and Environmental Engineering, University of Waterloo, Canada
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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
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Extreme weather conditions and changes in humidity rates significantly affect the concrete compressive strength development. Concrete as one of the substantial material used in residential buildings and infrastructures is subjected to a massive strength change under extreme weather conditions. For understanding, the different concrete’s behavioral aspects, various commercial cement types under different temperatures, and humidity rates are investigated in this chapter. The experiments are aimed to investigate the concrete strength development over time when the material is cast at lower to mild temperatures and different humidity index rates. Results show that reducing the curing temperature more than 15° could result in 20% reduction in total compressive strength, while decreasing humidity rates by 50% leads to less than 10% drop in ultimate strength. To understand the strength developing process, maturity tests are conducted. It is shown that concrete is not able to reach to the expected ultimate strength if the temperature is significantly low regardless of curing time. The effect of temperature change during the curing process is more tangible on strength development compared to cement type and humidity rate values.",book:{id:"8757",slug:"compressive-strength-of-concrete",title:"Compressive Strength of Concrete",fullTitle:"Compressive Strength of Concrete"},signatures:"Alireza Farzampour",authors:null},{id:"51720",doi:"10.5772/64574",title:"Microstructure of Concrete",slug:"microstructure-of-concrete",totalDownloads:4833,totalCrossrefCites:15,totalDimensionsCites:19,abstract:"Concrete is a composite material that consists of a binding medium and aggregate particles and can be formed in several types. It may be considered to consist of three phases: a cement paste, the aggregate, and the interfacial transition zone (ITZ) between them. In addition to ordinary Portland cement, the essential components of the base of concrete are aggregates and water. For practical requirements, additives and admixtures can be added to these raw materials to improve some desirable characteristics. The following requirements should be considered in producing high performance concrete (HPC): (i) low water/cement (w/c) ratio; (ii) fine aggregate; (iii) large quantity of mineral additives, silica fume, and fly ash; (iv) high dosage of superplasticizer; and (v) high-pressure steam curing. The microstructure of high performance concrete (HPC) is more homogenous than that of normal concrete (NC) due to the physical and chemical contribution of the additives (silica fume and fly ash) as well as it is less porous due to reduced w/c ratio with the addition of a superplasticizer. Inclusion of additives (individually or in combination) helped in improving the strength and durability of concrete mixes due to the additional reduction in porosity of cement paste and an improved interface between it and the aggregate.",book:{id:"5214",slug:"high-performance-concrete-technology-and-applications",title:"High Performance Concrete Technology and Applications",fullTitle:"High Performance Concrete Technology and Applications"},signatures:"Ameer A. Hilal",authors:[{id:"180518",title:"Dr.",name:"Ameer",middleName:null,surname:"Hilal",slug:"ameer-hilal",fullName:"Ameer Hilal"}]},{id:"51861",doi:"10.5772/64779",title:"Concretes with Photocatalytic Activity",slug:"concretes-with-photocatalytic-activity",totalDownloads:2826,totalCrossrefCites:8,totalDimensionsCites:15,abstract:"This chapter is a short review about the modified concretes with photocatalytic activity. In the beginning, the photocatalysis process is explained; the authors are focused on the mechanism of organic contamination and nitrogen oxide decomposition. Next the three main methods for concretes modification are presented: the first group is when the concrete is covered by thin layer of TiO2 materials, e.g., paints or TiO2 suspensions. The second group is the concretes with thick layer of photoactive concrete on the top. The third group constitutes concretes modified in mass with TiO2. The two main methods for photocatalytic activity of the modified concrete determination were shown: an air purification by a nitrogen oxide decomposition and the self-cleaning properties by dyes decomposition. Also in this chapter the mechanical properties of the modified concrete are presented. In the end, the examples of the buildings made of photocatalytic concretes are shown.",book:{id:"5214",slug:"high-performance-concrete-technology-and-applications",title:"High Performance Concrete Technology and Applications",fullTitle:"High Performance Concrete Technology and Applications"},signatures:"Magdalena Janus and Kamila Zając",authors:[{id:"180824",title:"Associate Prof.",name:"Magdalena",middleName:null,surname:"Janus",slug:"magdalena-janus",fullName:"Magdalena Janus"}]},{id:"64801",doi:"10.5772/intechopen.82489",title:"Bitumen and Its Modifier for Use in Pavement Engineering",slug:"bitumen-and-its-modifier-for-use-in-pavement-engineering",totalDownloads:1544,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter focuses on bitumen specifically. This chapter consists of several parts that can be mentioned, including the history of the appearance of bitumen and the types of constituent elements, as well as its mechanical properties and chemical structure and its thermal sensitivity. In all parts, the effects of bitumen on asphalt are discussed. In the following sections, the bitumen modification mechanism, polymer modifiers, and their behavior on the bitumen resistance to asphalt failures are also discussed. This chapter is very suitable for students and researchers interested in improving polymerization asphalt and bitumen and will help them to carry out research and concepts.",book:{id:"8412",slug:"sustainable-construction-and-building-materials",title:"Sustainable Construction and Building Materials",fullTitle:"Sustainable Construction and Building Materials"},signatures:"Mehrdad Honarmand, Javad Tanzadeh and Mohamad Beiranvand",authors:[{id:"268734",title:"M.Sc.",name:"Mehrdad",middleName:null,surname:"Honarmand",slug:"mehrdad-honarmand",fullName:"Mehrdad Honarmand"},{id:"271251",title:"Prof.",name:"Javad",middleName:null,surname:"Tanzadeh",slug:"javad-tanzadeh",fullName:"Javad Tanzadeh"}]},{id:"64787",doi:"10.5772/intechopen.82525",title:"A Decade of Research on Self-Healing Concrete",slug:"a-decade-of-research-on-self-healing-concrete",totalDownloads:1448,totalCrossrefCites:7,totalDimensionsCites:9,abstract:"The main findings of a decade of research on the design and development of the first self-healing concrete are summarized in this chapter. The autonomous healing concept is introduced, and plethora of design campaigns is enlisted. Healing agent encapsulation and agent tubes vascular networks are reported as the most efficient healing configurations for laboratory-scale and real-size applications, respectively. Crack formation, closure after healing and further damage are phenomena tracked by using advanced experimental monitoring methods and their performance is critically revised. The effect of self-healing technology on concrete mechanical response, durability and long-term response to damage are critically discussed. The study contributes to the open discussion in the scientific research community regarding self-healing concrete upscaling feasibility and finally it aims to contribute as a base for the future studies dealing with concrete design optimization.",book:{id:"8412",slug:"sustainable-construction-and-building-materials",title:"Sustainable Construction and Building Materials",fullTitle:"Sustainable Construction and Building Materials"},signatures:"Eleni Tsangouri",authors:[{id:"263163",title:"Ph.D.",name:"Eleni",middleName:null,surname:"Tsangouri",slug:"eleni-tsangouri",fullName:"Eleni Tsangouri"}]}],mostDownloadedChaptersLast30Days:[{id:"70605",title:"Designing a Tunnel",slug:"designing-a-tunnel",totalDownloads:2722,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Designing a tunnel is always a challenge. For shallow tunnels under cities due to the presence of buildings, bridges, important avenues, antiquities, etc. at the surface and other infrastructures in the vicinity of underground tunnels, parameters like vibrations and ground settlements must be tightly controlled. Urban tunnels are often made in soils with very low values of overburden. Risks of collapse and large deformations at the surface are high; thus negative impact on old buildings are likely to occur if appropriate measures are not taken in advance, when designing and constructing the tunnel. For deep tunnels with high overburden and low rock mass properties, squeezing conditions and excessive loads around the excavation can jeopardize the stability of the tunnel, leading to extensive collapse. The aim of the chapter is to give details on advance computational modelling and analytical methodologies, which can be used in order to design shallow and deep tunnels and to present real case studies from around the world, from very shallow tunnels in India with only 4.5 m overburden to a deep tunnel in Venezuela with extreme squeezing conditions under 1300 m overburden.",book:{id:"7690",slug:"tunnel-engineering-selected-topics",title:"Tunnel Engineering",fullTitle:"Tunnel Engineering - Selected Topics"},signatures:"Spiros Massinas",authors:[{id:"295762",title:"Dr.",name:"Spiros",middleName:null,surname:"Massinas",slug:"spiros-massinas",fullName:"Spiros Massinas"}]},{id:"70990",title:"Engineering Geology and Tunnels",slug:"engineering-geology-and-tunnels",totalDownloads:1934,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Currently, knowledge and understanding of the role of geological material and its implication in tunnel design is reinforced with advances in site investigation methods, the development of geotechnical classification systems and the consequent quantification of rock masses. However, the contribution of engineering geological information in tunnelling cannot be simply presented solely by a rock mass classification value. What is presented in this chapter is that the first step is not to start performing numerous calculations but to define the potential failure mechanisms. After defining the failure mechanism that is most critical, selection of the suitable design parameters is undertaken. This is then followed by the analysis and performance of the temporary support system based on a more realistic model. The specific failure mechanism is controlled and contained by the support system. A tunnel engineer must early assess all the critical engineering geological characteristics of the rock mass and the relevant mode of failure, for the specific factors of influence, and then decide either he or she will rely on a rock mass classification value to characterise all the site-specific conditions. Experiences from the tunnel behaviour of rock masses in different geological environments in Alpine mountain ridges are presented in this chapter.",book:{id:"7690",slug:"tunnel-engineering-selected-topics",title:"Tunnel Engineering",fullTitle:"Tunnel Engineering - Selected Topics"},signatures:"Vassilis Marinos",authors:[{id:"298713",title:"Associate Prof.",name:"Vassilis",middleName:null,surname:"Marinos",slug:"vassilis-marinos",fullName:"Vassilis Marinos"}]},{id:"51720",title:"Microstructure of Concrete",slug:"microstructure-of-concrete",totalDownloads:4833,totalCrossrefCites:15,totalDimensionsCites:19,abstract:"Concrete is a composite material that consists of a binding medium and aggregate particles and can be formed in several types. It may be considered to consist of three phases: a cement paste, the aggregate, and the interfacial transition zone (ITZ) between them. In addition to ordinary Portland cement, the essential components of the base of concrete are aggregates and water. For practical requirements, additives and admixtures can be added to these raw materials to improve some desirable characteristics. The following requirements should be considered in producing high performance concrete (HPC): (i) low water/cement (w/c) ratio; (ii) fine aggregate; (iii) large quantity of mineral additives, silica fume, and fly ash; (iv) high dosage of superplasticizer; and (v) high-pressure steam curing. The microstructure of high performance concrete (HPC) is more homogenous than that of normal concrete (NC) due to the physical and chemical contribution of the additives (silica fume and fly ash) as well as it is less porous due to reduced w/c ratio with the addition of a superplasticizer. 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The effectiveness of adhesive application, glue bond development and glue penetration into the wood structure is becoming more and more important as more structural glued timber products are used in construction and other applications. The continued increase in utilisation of mass timber products (MTPs) such as CLT, glulam and LVL in tall timber buildings requires an accurate and in-depth understanding of adhesive roles and their performance effectiveness during the life span of any of those products in relation to the type of loading applied, environmental effects (e.g. RH and temperature) and in-service condition of elements (e.g. exposure to major wet events and degradation from decay). This review aims to provide a comprehensive summary of existing imaging and other visualisation methods used to assess the glue line properties and examine the performance of glue lines in relation to factors such as species, product type and environmental conditions during manufacture and in-service life.",book:{id:"10584",slug:"engineered-wood-products-for-construction",title:"Engineered Wood Products for Construction",fullTitle:"Engineered Wood Products for Construction"},signatures:"Maryam Shirmohammadi and William Leggate",authors:[{id:"346973",title:"Dr.",name:"Maryam",middleName:null,surname:"Shirmohammadi",slug:"maryam-shirmohammadi",fullName:"Maryam Shirmohammadi"},{id:"426650",title:"Dr.",name:"William",middleName:null,surname:"Leggate",slug:"william-leggate",fullName:"William Leggate"}]},{id:"78315",title:"Engineered Wood Products as a Sustainable Construction Material: A Review",slug:"engineered-wood-products-as-a-sustainable-construction-material-a-review",totalDownloads:389,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Engineered wood products are considered as best building materials due to environmentally friendly. Huge change to the way in which wood has been utilized in primary application of construction in the course of the most recent 25 years are in light of decreased admittance to high strength timber from growth forests, and the turn of events and creation of various new design of manufactured wood products. Engineered wood products are available in different variety of sizes and measurements like laminated veneer lumber, glued laminated timber, finger jointed lumber, oriental strand board etc. It is utilized for rooftop and floor sheathing, solid structure, beams and the hull of boats. This review objectively explores not only the environmental aspects of the use of different engineered wood composites as a building material, but also their economic aspects, to understand their effect on sustainability.",book:{id:"10584",slug:"engineered-wood-products-for-construction",title:"Engineered Wood Products for Construction",fullTitle:"Engineered Wood Products for Construction"},signatures:"Ranjana Yadav and Jitendra Kumar",authors:[{id:"335083",title:"Dr.",name:"Jitendra",middleName:null,surname:"Kumar",slug:"jitendra-kumar",fullName:"Jitendra Kumar"},{id:"354856",title:"Dr.",name:"Dr Ranjana",middleName:null,surname:"Yadav",slug:"dr-ranjana-yadav",fullName:"Dr Ranjana Yadav"}]}],onlineFirstChaptersFilter:{topicId:"284",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:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,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:112,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,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:16,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:4,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). 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