Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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She worked at Neutec Ltd. as Arge Analyst. As a lecturer Dr. Yasemin Yıldız received an invitation from the University of Pristina to study at the Chemistry Department, Faculty of Education at Prizren University in 2014. During her visit her research was related to membrane preparation, extraction and metals separation, membrane stability and lifetime. She now works at Sakarya University.",institutionString:"Sakarya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Sakarya University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"208159",title:"Dr.",name:"Aynur",middleName:null,surname:"Manzak",slug:"aynur-manzak",fullName:"Aynur Manzak",profilePictureURL:"https://mts.intechopen.com/storage/users/208159/images/system/208159.jpeg",biography:"Aynur Manzak received her B.S (1999) and Ph.D. (2005) degrees in Physical Chemistry from Sakarya University. Aynur Manzak worked on a post-doctoral in United States. During the research visit, she researched extraction and polymer electrodes. She later continued her work at Sakarya University.",institutionString:"Sakarya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Sakarya University",institutionURL:null,country:{name:"Turkey"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"950",title:"Solid-State Chemistry",slug:"metals-and-nonmetals-solid-state-chemistry"}],chapters:[{id:"69224",title:"Introductory Chapter: Cobalt Compounds and Applications",doi:"10.5772/intechopen.89404",slug:"introductory-chapter-cobalt-compounds-and-applications",totalDownloads:761,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Aynur Manzak and Yasemin Yildiz",downloadPdfUrl:"/chapter/pdf-download/69224",previewPdfUrl:"/chapter/pdf-preview/69224",authors:[{id:"208129",title:"Dr.",name:"Yasemin",surname:"Yıldız",slug:"yasemin-yildiz",fullName:"Yasemin Yıldız"}],corrections:null},{id:"67215",title:"Cobalt Phosphates and Applications",doi:"10.5772/intechopen.86215",slug:"cobalt-phosphates-and-applications",totalDownloads:908,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Cobalt phosphates with open framework present various physical performances in relation to their structures. In fact, the development of new materials that could potentially be ionic conductors or ion exchangers led us to examine the Co-P-O and A-Co-P-O crystallographic systems (A: monovalent cation) and their different methods of synthesis. This work consists first of all in highlighting the crystalline phases of cobalt phosphates. Indeed, many works related to the discovery of some of these materials with interesting properties, in particular ionic conductivity, motivated our research and encouraged us to collect several cobalt phosphates and to correlate structure-physical properties in particular electrical properties.",signatures:"Riadh Marzouki, Mahmoud A. Sayed, Mohsen Graia and Mohamed Faouzi Zid",downloadPdfUrl:"/chapter/pdf-download/67215",previewPdfUrl:"/chapter/pdf-preview/67215",authors:[{id:"290142",title:"Dr.",name:"Riadh",surname:"Marzouki",slug:"riadh-marzouki",fullName:"Riadh Marzouki"},{id:"297176",title:"Prof.",name:"Mohsen",surname:"Graia",slug:"mohsen-graia",fullName:"Mohsen Graia"},{id:"297177",title:"Prof.",name:"Mohamed Faouzi",surname:"Zid",slug:"mohamed-faouzi-zid",fullName:"Mohamed Faouzi Zid"},{id:"304250",title:"Dr.",name:"Mahmoud",surname:"Sayed",slug:"mahmoud-sayed",fullName:"Mahmoud Sayed"}],corrections:null},{id:"68723",title:"The Cobalt Oxide-Based Composite Nanomaterial Synthesis and Its Biomedical and Engineering Applications",doi:"10.5772/intechopen.88272",slug:"the-cobalt-oxide-based-composite-nanomaterial-synthesis-and-its-biomedical-and-engineering-applicati",totalDownloads:881,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:"The magnetic nanoparticles (NPs) are offering a wide range of applications in medical and engineering fields. Among all the magnetic nanoparticles, cobalt oxide (Co3O4) nanoparticles and its composite-based nanoparticles are attracting more interest from researchers because of its unique mechanical, thermal, and magnetic properties. The aim of this book is to bring together a number of recent contributions regarding the cobalt oxide-based composite nanoparticles from several researchers all over the world. The latest research results, innovations, and methodologies are reported in the book in order to support the discussion and to circulate ideas and knowledge about the applications of these materials in medical and engineering applications. This chapter presents the methodology for the synthesis and characterization and applications of cobalt oxide-based composite nanoparticles. The detailed analysis related to toxicity of these nanocomposite materials is also included in this book chapter.",signatures:"Lingala Syam Sundar, Manoj K. Singh, António M.B. Pereira and Antonio C.M. Sousa",downloadPdfUrl:"/chapter/pdf-download/68723",previewPdfUrl:"/chapter/pdf-preview/68723",authors:[{id:"290177",title:"Dr.",name:"Syam Sundar",surname:"Lingala",slug:"syam-sundar-lingala",fullName:"Syam Sundar Lingala"}],corrections:null},{id:"68787",title:"Cobalt-Based Catalysts for CO Preferential Oxidation",doi:"10.5772/intechopen.88976",slug:"cobalt-based-catalysts-for-co-preferential-oxidation",totalDownloads:718,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this work, catalysts based on cobalt supported on ZrO2 and CeO2 and CoCeMnOx were studied for the CO preferential oxidation (COPrOx) in hydrogen-rich stream able to feed fuel cells. Among them, the CoCeMnOx formulation showed the highest CO conversion at low temperatures, while the cobalt oxide supported on ceria presented the best selectivity toward CO2. The Co3O4 spinel was the active phase for the CO preferential oxidation detected in all catalysts. However, the CoOx-CeO2 and CoCeMnOx catalysts resulted more active than cobalt oxide supported on zirconia. The presence of ceria close to cobalt species promotes the redox properties and enhances the catalytic activity. In the CoCeMnOx catalyst prepared by coprecipitation, the incorporation of Mn represented an additional positive effect. The presence of Mn promoted the reoxidation of Co2+ to Co3+ and, consequently, the activity increased at low temperature. By X-ray diffraction (XRD) of CoOx-ZrO2 and the CoOx-CeO2 catalysts, the Co3O4 spinel and ZrO2 or CeO2 were identified in agreement with laser-Raman spectra. At the same time, the CoCeMnOx catalyst, prepared by coprecipitation of precursor salts, showed an incipient development of a new phase (Mn,Co)3O4 mixed spinel, due to the intimate contact between elements.",signatures:"Leticia E. Gómez and Alicia V. Boix",downloadPdfUrl:"/chapter/pdf-download/68787",previewPdfUrl:"/chapter/pdf-preview/68787",authors:[{id:"282809",title:"Prof.",name:"Alicia",surname:"Boix",slug:"alicia-boix",fullName:"Alicia Boix"},{id:"282816",title:"Dr.",name:"Leticia",surname:"Gomez",slug:"leticia-gomez",fullName:"Leticia Gomez"}],corrections:null},{id:"70124",title:"Cobalt Single Atom Heterogeneous Catalyst: Method of Preparation, Characterization, Catalysis, and Mechanism",doi:"10.5772/intechopen.85773",slug:"cobalt-single-atom-heterogeneous-catalyst-method-of-preparation-characterization-catalysis-and-mecha",totalDownloads:917,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Transition metal nanoparticles and metal oxide have been used extensively for a wide range of applications in electrochemical reactions (HER, ORR, OER) and energy storage (supercapacitors batteries). To make less expensive, the use of transition metal at minimum metal contents without compromising the catalytic activity could be one way. Most of the catalytic process takes place on the surface and reaction dynamic can be manipulated by changing the particle size and shape. For a long time, single metal atom organometallic compounds have been used as a catalyst at the industrial level. However, problems with the homogeneous catalyst to recover back at the end of the process lead to development of heterogeneous single-atom catalysts with equal activity like a homogeneous catalyst. Cobalt single atom has received a tremendous interest of the scientific community due to its excellent catalytic activity and recyclability. Cobalt single-atom catalyst has shown better performance compared with sub-nanometer nanoparticles catalyst for ORR, OER, and HER. This chapter is conferring method of preparation of carbon-based single Co atoms heterogeneous catalyst, their application for ORR, OER, HER reactions, and mechanistic investigations through DFT calculations. The role of single Co metal atoms and anchoring using N or heteroatoms is discussed and compared.",signatures:"Baljeet Singh, Surender Kumar and Archana Singh",downloadPdfUrl:"/chapter/pdf-download/70124",previewPdfUrl:"/chapter/pdf-preview/70124",authors:[{id:"283756",title:"Dr.",name:"Surender",surname:"Kumar",slug:"surender-kumar",fullName:"Surender Kumar"},{id:"284102",title:"Dr.",name:"Baljeet",surname:"Singh",slug:"baljeet-singh",fullName:"Baljeet Singh"}],corrections:null},{id:"67173",title:"Perovskite-Type Lanthanum Cobaltite LaCoO3: Aspects of Processing Route toward Practical Applications",doi:"10.5772/intechopen.86260",slug:"perovskite-type-lanthanum-cobaltite-lacoo-sub-3-sub-aspects-of-processing-route-toward-practical-app",totalDownloads:1024,totalCrossrefCites:3,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Lanthanum cobaltite (LaCoO3) perovskite-type oxide is an important conductive ceramic material finding a broad range of technical applications. Physical and chemical properties of the final lanthanum cobalt oxide powder material obtained are strongly dependent on the method of preparation. Taking in account these considerations, we focus our investigation on the solid state reaction process. The characterization of prepared lanthanum cobalt oxide material was studied by using X-ray diffractometry (XRD), scanning electron microscopy (SEM), thermogravimetry-differential scanning calorimetry (TG-DSC), and conduction properties. Following the experimental results, it can be concluded that with proper improvement, the solid state reaction process may also provide an efficient preparation method for perovskite-type LaCoO3 powder. Important to mention is that we looked into the aspects to produce again same which showed consistently reproducibility of batch to batch powder properties. This is a key factor to overcome a successful commercialization of new material synthesis development.",signatures:"Mirela Dragan, Stanica Enache, Mihai Varlam and Konstantin Petrov",downloadPdfUrl:"/chapter/pdf-download/67173",previewPdfUrl:"/chapter/pdf-preview/67173",authors:[{id:"243884",title:"Dr.",name:"Mihai",surname:"Varlam",slug:"mihai-varlam",fullName:"Mihai Varlam"},{id:"288747",title:"Dr.",name:"Mirela",surname:"Dragan",slug:"mirela-dragan",fullName:"Mirela Dragan"},{id:"290510",title:"Dr.",name:"Stanica",surname:"Enache",slug:"stanica-enache",fullName:"Stanica Enache"},{id:"290513",title:"Dr.",name:"Konstantin",surname:"Petrov",slug:"konstantin-petrov",fullName:"Konstantin Petrov"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3129",title:"Physics and Technology of Silicon Carbide Devices",subtitle:null,isOpenForSubmission:!1,hash:"8635479660e93cb1129f0a92cf15a124",slug:"physics-and-technology-of-silicon-carbide-devices",bookSignature:"Yasuto Hijikata",coverURL:"https://cdn.intechopen.com/books/images_new/3129.jpg",editedByType:"Edited by",editors:[{id:"18137",title:"Dr.",name:"Yasuto",surname:"Hijikata",slug:"yasuto-hijikata",fullName:"Yasuto Hijikata"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6215",title:"Graphene Materials",subtitle:"Advanced Applications",isOpenForSubmission:!1,hash:"3a921aba41351ab84fd7a9b4ea63914d",slug:"graphene-materials-advanced-applications",bookSignature:"George Z. 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\n
1. Introduction
\n
Biomedical application of EPR has gained momentum in recent times. All atoms and molecules cannot be studied by EPR technique. Atoms and molecules with electronic magnetic moment and angular momentum can be studied with this method. Four classes of compounds with biological properties stand out in EPR studies:
odd molecules and free radicals,
biradicals,
triplet electronic states and
transition element ions.
\n
In these, single molecules and free radicals can occur biologically in the following situations: univalent redox reactions, enzymatic oxidizations (dehydrogenations), radiation damage and photosynthesis. The biomedical application of electron paramagnetic resonance (EPR) has been grouped together under five headings:
The study of free radicals in living tissue.
The relation between free radicals and carcinogenic activity.
The study of oxidation-reduction systems and enzyme interaction.
Photosynthesis and optical absorption studies.
X-irradiation of biological material.
\n
\n
\n
2. The EPR study of free radicals in living tissue
\n
The first study of free radical concentration in living tissues by EPR was conducted by Commoner et al. [1]. The presence of water in biological materials poses difficulties in EPR studies. The interaction of the large dipole moment with the microwave electric field in the liquid phase causes a large quenching and a Q factor decrease. This can be corrected using smaller samples (e.g. sample tubes of 1-mm diameter instead of the normal 5-mm diameter). Working with a high radiofrequency instead of microwaves region can be useful to obtain high sensitivity for aqueous studies. The loss due to the dipole interaction falls with a decreasing frequency. At lower frequencies, a larger volume should be used to increase sensitivity. Such a situation is suitable for free radical concentration studies.
\n
If the experiments are carried out in the microwave area, the loss from water can be removed by freezing the sample and by making the measurements at liquid nitrogen temperatures, or by freezing and drying the material before it is placed in the cavity. Radicals can be adversely affected in both methods. In this case, studies with smaller sample tubes should be preferred at room temperature. Commoner et al. [1] prepared their first samples by free-drying by taking them from many different tissues. Thus, the powder samples were run on an X-band EPR spectrometer. The first results are given in Table 1. In metabolically active tissues such as green leaves, liver and kidney, it was noticed that there was a higher content of free radicals. In addition, the free radical concentration was found to be associated with protein components. It has also been shown by fractionation experiments that protein denaturation destroys the radical concentration.
\n
\n
\n
\n\n
\n
Material
\n
Radical concentration (10−8 mole/g of dry weight)
\n
\n\n\n
\n
Nicotiana tabacum, leaf
\n
65
\n
\n
\n
Nicotiana tabacum, roots
\n
10
\n
\n
\n
Coleus, leaf
\n
180
\n
\n
\n
Barley, leaf
\n
25
\n
\n
\n
Digitalis, germinating seeds
\n
10
\n
\n
\n
Carrot, root
\n
8
\n
\n
\n
Beet, root
\n
6
\n
\n
\n
Rabbit, blood
\n
25
\n
\n
\n
Rabbit, muscle
\n
20
\n
\n
\n
Rabbit, brain
\n
25
\n
\n
\n
Rabbit, liver
\n
60
\n
\n
\n
Rabbit, lung
\n
30
\n
\n
\n
Rabbit, heart
\n
35
\n
\n
\n
Rabbit, kidney
\n
55
\n
\n
\n
Frog, eggs
\n
200
\n
\n
\n
Drosophila, entire
\n
4
\n
\n\n
Table 1.
Radical concentration in different tissues.
\n
According to the results obtained from studies done with ungerminated and germinated seeds and with leaves exposed to varying amounts of illumination, increasing the free radical concentration is associated with a high metabolic activity. For this reason, although no measurable free radical concentration was found in samples prepared from digitalis seeds before germination, a free radical concentration of 10−7 moles/g was obtained from the seeds obtained by the emergence of the primary root.
\n
These radical concentrations are associated with proteins, reach concentrations varying according to the level of metabolic activity and have the magnitudes consistent with the total electron-transporting content of the tissues [2].
\n
Commoner et al. [1] identified the presence of a high free radical concentration in melanin, a pigmentation found in various biological tissues, Melanin formation in animals by UV or ionizing radiation [3]. This is evidence that free radical production takes place with irradiation of living tissue.
\n
\n
\n
3. EPR study of free radicals and carcinogenic activity
\n
Some researchers have acknowledged that free radicals participate in carcinogenic activity [4, 5]. Lipkin et al. [5] suggested that the carcinogenic activities of some large ring structures, together with mild reductive agents, could create negative ion-free radicals. Non-carcinogenic hydrocarbons, such as naphthalene, have also been shown to require very strong reducing agents before such radicals can be formed. Electron paramagnetic resonance is a powerful technique to test the accuracy of these findings.
\n
Several experiments have recently been carried out on the radical concentration in cigarette smoke [6]. The arrangement in which the cigarettes are fixed to a filter pump [7] is shown in Figure 1. Existing active radicals remain unchanged in the frozen state in the apparatus. After the freezing process is done, when the tube and the contents are processed in the EPR spectrometer for the radical concentration measurement process, it is possible to differentiate between short-lived active radicals and stabilizing radicals.
\n
Figure 1.
An apparatus for trapping cigarette smoke at low temperatures.
\n
The concentration of radicals obtained in the frozen smoke condensate before warming was of the order of 1015 free electrons per gram. It should be noted that this condensate contains large amounts of solid carbon dioxide and ice. On warming, the condensate separated into an aqueous and an organic or a tarry phase. No radical concentration at all could be detected in the aqueous phase, and that in the organic phase was reduced by a factor of approximately six. The radicals that could still be detected in the latter were found to be highly stabilized, and no diminution of their concentration was found after several days. It would therefore appear from these experiments that the tar constituents of cigarette smoke contain about 6 × 1015 free electron/gram. Some of these radicals, being relatively short-lived, disappear when the condensate is warmed to 60°C for some minutes. The remainder, however, appears to be very stable and long-lived. It is probable that these stable radicals are very similar to those formed by pyrolysis of other organic matter.
\n
These experiments therefore show that there is a relatively high concentration of both active and stabilized free radicals in cigarette smoke when it is first formed, and it is possible that either or both of these might act as carcinogenic agents. It is important to note in this connection that most bioassays in tobacco carcinogenesis have been carried out using relatively old condensates, and it is now evident that these will be deficient in the unstable free radicals initially present in the smoke.
\n
The subject of carcinogenesis still needs to be resolved and understood. When the effects of various carcinogenic agents such as sodium hydroxide, ultraviolet and ionizing radiation and thousands of organic compounds are examined, a free radical intermediate always plays a role. Although there is no direct evidence to date, smog studies and recent work by Lyons et al. [6] have found that soot and tobacco smoke contain highly active radicals and signaled possible links with lung cancer.
\n
The concentration of stable free radicals in atmospheric soot is about 100 times larger than in cigarette smoke, but as with the polycyclic hydrocarbons [8], adsorption on comparatively larger particles and further stabilization as a result are likely to render them inaccessible to the cells. It is evident that a large amount of systematic work will have to be performed before the correlation between free radical concentration and carcinogenic activity is established, but these initial experiments show that electron resonance should be of considerable help in these studies.
\n
\n
\n
4. EPR study of oxidation: reduction and enzyme systems
\n
It has already been seen that free radicals have been postulated as necessary intermediates in biological oxidation-reduction systems [9] and that the preliminary measurements of Commoner et al. [1] appear to support this hypothesis. Free radical processes have also been postulated as taking part in most enzyme reactions [10], and kinetic studies often show that chain processes are present. A large number of electron resonance studies of enzyme reactions are now in progress to investigate the details of these reaction mechanisms. At the time of writing, no detailed results on actual enzyme systems have been published, but some preliminary basic work on simpler oxidation-reduction systems has been reported.
\n
One series of organic compounds closely related to biologically important molecules are the phthalocyanines. These are large planar molecules consisting of a conjugated ring system very similar to that of the porphyrin ring and containing either two protons or a divalent metal atom at the center. If these are oxidized by such agents as ceric sulfate, a two-stage oxidation process takes place via a transient intermediate stage which often gives the solution a markedly different color for a few seconds. There has been considerable speculation [11] as to whether this intermediate oxidation stage involved a change of valency of the central metal atom or the liberation of an unpaired electron in the ring system. Electron resonance studies are able to give a very direct answer to such a problem as this, since different valence states of the central metal atom will have characteristic g-values well displaced from the free-spin value, whereas a mobile electron in the ring system will have a narrow ‘free radical’ resonance line very close to g = 2.0.
\n
It was found experimentally [12] that all the phthalocyanines studied had intermediate oxidation states that gave a narrow resonance line with a g-value very close to that of a free spin. This was therefore conclusive proof that the oxidation process involved mobile electrons in the conjugated ring system. In some cases [12], it was possible to follow the oxidation process through its different stages and watch the growth and decay of the intermediate on the oscilloscope of the resonance spectrometer.
\n
Another oxidation system of considerable biological importance is the oxidation of ferrihemoglobin to its metastable state. This system has been studied in some detail [13, 14] by electron resonance. The systematic analysis of these results is a good illustration of the fact that it is important to consider all possible interactions when investigating biological systems. As in the case of the phthalocyanines, the oxidation intermediate will either involve an unpaired electron in the conjugated ring system or a change in the valency state of the central iron atom. Chemical investigations [15] give inconclusive evidence as to which of these mechanisms is actually present.
\n
In the initial electron resonance studies [13], it was found that a strong narrow free radical line with a g-value of 2.0023 was obtained; methemoglobin or metmyoglobin was oxidized by hydrogen peroxide or periodate. By analogy with the results obtained from the phthalocyanines, it was therefore assumed that the oxidation involved electron removal from the π-orbitals of the porphyrin ring. Furthermore detailed and systematic investigations of this system [14] confirmed that there is a close connection between the free radical and the peroxide compound, as shown by four separate sets of results. First, the formation of the free radical is specific for the methemoglobin peroxide reaction, since it does not occur in model systems such as serum albumin-Fe-H2O2 or metmyoglobin cyanide-Fe-H2O2. Secondly, the removal of excess peroxide by catalase does not affect the free radical. Thirdly, the amount of free radical is proportional to the initial concentration of metmyoglobin, under comparable conditions. Fourthly, the free radical is destroyed by substances reducing the peroxide compound (ferrocyanide, nitrite, iodide, p-cresol).
\n
In spite of the above conclusions, however, there are further results which show that the free radical cannot be identified with the peroxide compound itself. The reasons for this can be summarized as follows. First, the calculated concentration of free radical in most favorable case was only 9% of the peroxide compound. Secondly, its concentration varied widely under conditions in which the amount of peroxide compound remained approximately constant. Thus, an increase of pH from 6 to 10 decreased the free radical concentration by 80%, while the peroxide compound was formed equally well at these pH values. Thirdly, the preaddition of stoichiometric quantities of ferrocyanide to the metmyoglobin before the formation of peroxide compound almost eliminated the free radical. Such treatment has been found [15] to remove the first oxidizing equivalent of hydrogen peroxide lost during the formation of the peroxide compound.
\n
These experiments therefore suggest that the free radical is not the peroxide compound itself, but a product of oxidation by the first oxidizing equivalent, which is likely to be a hydroxyl radical [15]. The free radical signal is thus probably due to oxidation of part of the globin molecule, and although it takes place at the same time as the peroxide compound is formed, it is not associated directly with this oxidation mechanism. It is nevertheless of considerable interest as it is an example of a reversible univalent oxidation state in a biological system which does not involve valence changes of a transition metal. The fact that the formation of the actual peroxide compound involved a change in the binding of the iron atom was demonstrated conclusively by observing the metmyoglobin resonance at g = 6.0 [16] as oxidation occurred. This resonance was found to decrease as the peroxide compound was formed, indicating a change from ionic to covalent binding [17] as the oxidation took place.
\n
It may be noted in this connection that a detailed study of the different derivatives of hemoglobin by electron resonance not only allows the actual orbitals involved in the binding to be determined [17] but also gives detailed structural information on the porphyrin and histidine planes [16, 17, 18, 19, 20].
\n
This work on the oxidation states of hemoglobin and myoglobin indicates the necessity for careful systematic studies if the electron resonance spectra of these biological systems are to be correctly interpreted. This remark will apply with an even greater force to the catalase and peroxidase [14] and other complex enzyme systems that are being currently investigated.
\n
It may be noted that a kinetic study of these enzyme reactions not only allows the variation of free radical concentration to be followed but also enables correlations to be made between this and the concentration of any paramagnetic atoms that are present. The exact role of different metallic ions in enzyme reactions has been a matter of speculation for some time, and in some cases, they are assumed to play an essential step in the oxidation-reduction mechanism, and in others, they appear to enter only as impurities. If the concentration of the metallic ions is monitored [21] at the same time as that of the free radicals, these effects can be clearly distinguished.
\n
The idea that free radicals can participate in biological processes has recently been explored. It has been suggested by Haber and Willstatter [22] that free radical intermediates form a large part of the enzymatic dehydrogenations. In the single electron transfer hypothesis of biological oxidation, most of the reactants in metabolic redox systems are double molecules. In this case, all the electrons in these molecules are found in pairs. Thus, it is considered that all of the electron transfers must be in pairs. In the two-electron transfer, certain molecules must be present which proceed by a one-electron step. An example of this is the process of delivering an electron under oxidation or reduction to metallo-organic substances of cytochrome. It has been suggested by Michaelis that all the oxidation of organic molecules proceeds in two successive stages and that free radical is an intermediate state [23]. Michaelis proved this experimentally.
\n
Spectrophotometric kinetic studies have shown that various biologically active substances such as free radicals are present as intermediates between fully reduced and fully oxidized states. Prior to the discovery of the electron paramagnetic resonance technique, static susceptibility measurements have been a direct method of detecting more than 10−6 moles of paramagnetic molecule solution. Brill [24] has recently successfully carried out an experiment that can detect a 10−7 molar solution of paramagnetic molecules. However, Pauling and Coryell [25] gave many values for the magnetic susceptibility of hemoglobin. The hypothesis of Michaelis was not confirmed with complete success due to this low sensitivity. Thus, EPR has greatly contributed to the distinction between paramagnetic ions, odd molecules and free radicals through increased sensitivity.
\n
There are many EPR studies related to non-enzymatic reduction of quinone and quinoid compounds [26]. Two consecutive one-electron transfers occur in these compounds. Furthermore, the lifetime of paramagnetic semi-quinone radicals depends on the isomeric form which is compatible with the differences in oxidation potentials and pH of the solution. While the free radical generated by the dehydrogenation of the hydroxyl group is stabilized in the alkaline solution, the free radical generated by the dehydrogenation of the amino group is stabilized in the acid solution. The compounds which give free radical concentrations are as follows:
If the lifetime of the free radical intermediate such as the parabenzoquinone redox reaction shown in Figure 2 is short, the probability of a polymeric reaction is reduced.
\n
Figure 2.
Quinone-hydroquinone redox reaction.
\n
Beinert [27], Commoner et al. [28] and Ehrenberg and Ludwig [29] conducted a number of studies on EPR studies of free radicals resulting from enzymatic oxidation-reduction reactions. Beinert has shown that the EPR signals observed for flavin enzyme and fatty acyl (CoA) dehydrogenase are associated with the re-oxidation of the enzyme-substrate complex by molecular oxygen [27]. However, more studies should be done to determine whether they will be confronted with other double flavin enzymes. Beinert could be shown by comparison with optical kinetics that the radicals observed in a single flavin enzyme and cytochrome reductase are intermediates in the enzyme substrate reaction itself.
\n
In enzyme chemistry, the detection of paramagnetic ions in enzymatic reactions is important. In this subject, EPR plays an important role. Bray et al. [30] investigated the role of molybdenum in xanthine oxidase reactions, despite the oxidation state; Malmstrom et al. [31] investigated the role of Mn++ in enolase reactions; Malmstrom et al. [32] investigated the role of Cu++ in laccase; Beinert and Sands [33] investigated the role of Cu++ in cytochrome oxidase and the role of Fe++ in cytochrome-reductase [34]. In addition, after all the iron reduction (28 per cent), Beinert and Sands [33] showed that no free radical signal reduced by DPNH was produced. Because DPN shows a reaction sequence in which the electron flow sequence progresses in the form of substrate→flavin→iron. The answer to whether or not the iron is in contact with other electron receivers can only give EPR.
\n
\n
\n
5. EPR studies on photosynthesis and optical absorption
\n
The free radicals play an important role in photosynthesis, and it had been proposed previously that the excitation of chlorophyll during photosynthesis involved mono- [9] or bi-radical [35] formation. In the initial experiments [1], the leaves were lyophilized before insertion into the cavity, and hence kinetic studies on the specimens were not possible. In a more recent series of experiments, however, Commoner, Heise and Townsend [36] were able to study aqueous suspensions of chloroplasts, in situ in the cavity, under different conditions of illumination. This was achieved by the use of very small specimen tubes in conjunction with a high-sensitivity 100-kc/s field modulation spectrometer.
\n
The chloroplasts, which are known to be responsible for the essential steps of photosynthesis [35], were prepared from leaves of Nicotiana tabacum by gentle hand maceration in an ice bath in a buffer solution of pH 8. After filtration and centrifugation, the chloroplasts were resuspended in 55% sucrose and stored in the cold. The spectrometer employed a reflection-type cavity and had a 2-mm diameter hole in the shorting end through which the light from a car headlamp was focused. In this way, the free radical concentration in the chloroplast suspension could be studied under different conditions of illumination, and the rate of growth and decay was measured accurately.
\n
It was found that there was only a very small radical concentration in the absence of any illumination, but that this increased by about sixfold as soon as the 50 c.p. headlamp was switched on. Rapid tracing of the signal enabled an accurate plot of the growth of radical concentration to be obtained. It was found that the concentration rose exponentially to a steady value after the onset of illumination with an exponential time constant of 12 s. The decay of radical concentration when the lamp was switched off was also of an exponential form, but with a somewhat longer constant of 45 s. These results show conclusively that a steady-state radical concentration was being measured and not a system of trapped or stabilized radicals.
\n
The variation of radical concentration with intensity and the wavelength of the incident illumination were also studied [36]. The concentration was found to rise with an increasing intensity but reached a saturation value at high levels, and this is also true of the photosynthetic activity of both chloroplasts and whole cells. It was also shown that the free radical concentration was produced by the same wavelength range 4000–7000 Å, which is responsible for photosynthesis. These experiments therefore provide conclusive evidence that one-electron intermediates with unstable molecular configurations are produced during photosynthetic reactions.
\n
Further measurements on illuminated chloroplasts were then made by Sogo et al. [37]. In particular, they studied the variation of radical rise and decay time with the temperature of the specimen. Their results are summarized in Table 2, and the most striking feature of these results is that the signal growth time is approximately the same when the chloroplasts are frozen at −140°C as when they are at room temperature. This fact would appear to rule out the ordinary enzymatic oxidation-reduction reactions as the free radical intermediates in photosynthesis. The longer decay time at −140°C also suggests that excitation to the triplet state is not responsible for the observed signal, and it is unlikely that this would be observed in any case. It would therefore seem that the intermediate associated with photosynthesis is some form of electron produced by a dissociated bond or trapped in a quasi-crystalline lattice. It is noticeable [37] in this connection that the lines at room temperature show evidence of exchange narrowing, but are wider at the lower temperatures, indicating a reduced mobility of the unpaired electrons.
\n
\n
\n
\n
\n
\n
\n\n
\n
Substance
\n
Light intensity (quanta/sec.)
\n
Temperature (°C)
\n
Signal growth time
\n
Signal decay time
\n
\n\n\n
\n
Dried leaves
\n
1015
\n
25
\n
Minutes
\n
Hours
\n
\n
\n
Dried whole chloroplasts
\n
1015
\n
25
\n
Minutes
\n
Hours
\n
\n
\n
60
\n
Seconds
\n
Seconds
\n
\n
\n
Wet whole chloroplast
\n
1015
\n
25
\n
Seconds
\n
1 minute
\n
\n
\n
−140
\n
Seconds
\n
Hours
\n
\n
\n
Wet small chloroplast fragments
\n
1015
\n
25
\n
Seconds
\n
Minutes
\n
\n
\n
Wet large chloroplast fragments
\n
1015
\n
24
\n
30 s
\n
30 s
\n
\n
\n
1016
\n
25
\n
6 s
\n
30 s
\n
\n
\n
1016
\n
−140
\n
10 s
\n
Hours
\n
\n\n
Table 2.
Growth and decay time of radical concentration in photosynthesis material.
\n
Tollin and Calvin [38] have also performed detailed studies of the luminescence of similar chloroplast samples and have correlated these results with the electron resonance measurements. As a result of this, it would appear that the hypothesis of electron trapping and the production of holes is the most plausible theory of photosynthetic reaction. This semi-conductor theory of chloroplast action has been proposed by several investigators [39, 40] and is also supported by glow-curve and resistance measurements [40]. In this theory, the luminescence that occurs immediately after illumination ceases will be largely due to radiative recombination of nearly free electrons and holes. Following this, the thermal excitation of electrons and holes from the shallowest traps will produce further emission, and the decay constant will be a function of the trap depth and the temperature. The close correlation of the luminescence and electron resonance is explained in this way, and also the much longer decay times obtained at low temperatures, when the thermal excitation energy is much smaller while the trap depth remains more or less the same.
\n
These initial electron resonance studies of photosynthesis are only of a preliminary nature, however, and the interpretation of the results must still be considered as somewhat speculative. They do illustrate very well, however, the kind of information that can be obtained, and the technique should prove to be a very powerful complement to all the normal luminescence and phosphorescence studies.
\n
Photosynthesis, the biochemical process in which photoenergy transforms into chemical energy, involves steps of oxidation reduction. Thus, EPR is one of the important methods that clarify the photosynthesis process. Calvin and Sogo [41] and Commoner et al. [28] observed light-sensitive EPR signals on the chlorophyll system. Other important work in this regard was carried out by Sogo et al. [37] and Tollin and Calvin [38].
\n
\n
\n
6. EPR study of X-irradiation of biological material
\n
A study of the breakdown processes that occur in living tissue as a result of X- or γ-ray irradiation is one of the most important problems in modern medical physics. Electron resonance is one of the most direct and sensitive methods of investigation in this particular field, and the initial results have already shown that a large variety of different spectra can be obtained from different specimens. The energy of the incident quanta is not only great enough to break a very large number of different bonds but the secondary radical and nonradical species can also produce further change in the cell structure. Thus, most biological specimens contain a large percentage of water, and it is known that the OH˙ radicals formed in this by primary photolysis will combine and produce relatively high concentrations of hydrogen peroxide. This is very toxic for a large number of cellular reactions and may easily produce breakdown processes, the products of which can then be further attacked by primary or secondary radicals. Deductions of the mode of breakdown from the observed electron resonance spectra should therefore be made very tentatively until all possible mechanisms have been considered.
\n
Electron resonance studies of this kind can be divided into two broad categories:
quantitative studies of free radical production as a function of radiation dosage and
qualitative analysis of the types of radical structure formed in the breakdown process.
\n
In quantitative studies, it is possible to study either the dynamic concentrations which are formed in situ in the resonator, or the larger concentrations obtained in a solid or a viscous medium by a suitable trapping technique. In order to obtain dynamic concentrations of sufficient intensity, it is necessary to employ very powerful radiation sources, and this often requires pulse techniques. The use of pulsed irradiation can also give useful additional information. Thus, it is possible, in principle, to trigger the electron resonance spectrometer at a specified time delay after the irradiation pulse and hence obtain a series of measurements on the free radical decay between successive pulses. A high sensitivity detection with long-time constants is not feasible under such conditions, however, and this is another reason why high radiation dosages must be employed. Several laboratories are working on systems suitable for these quantitative dynamic studies, but to date, most information has come from the qualitative analysis of the different radical structures present in the breakdown process.
\n
The identification of different radical species from the hyperfine pattern of their electron resonance spectra has been considered at some length. It was seen there that is often possible to pick out the presence of specific groups in the presence of other free radicals, and this method of analysis can now be extended to the more complex biological compounds. The results of Gordy et al. [40] on X-irradiated cystine and various fibrous proteins may be taken as a specific example of this. The electron resonance spectra of cystine, hair, nail and feather are obtained [42], and they are seen to be very similar. This similarity is even more striking when it is found that the spectra are not symmetrically placed around g = 2 and have splittings that vary with the strength of the external field. It would therefore appear that in each case, the free radicals must have an unpaired electron strongly localized on a sulfur or an oxygen atom with an associated anisotropic g-factor. It is noticeable in this connection that the spectra are very similar to those obtained from frozen solutions of sulfur in oleum [42].
\n
Gordy et al. [43] in fact explain these spectra as due to an unpaired electron localized on the S-S bond of the cystine. Thus, if an electron is ejected by the irradiation from some point in the molecule, the vacancy probably moves to the S atoms to form an additional lower energy three-electron bond.
\n
There is thus now a hole shared by the two sulfur atoms through exchange of their electrons, and the loss of an electron from the sulfur lone pair orbitals tends to strengthen rather than weaken the bond in this case.
\n
From the marked similarity of the spectra of the irradiated hair, feather and toe-nail, it would appear that the radicals in these proteins must also be associated with their cystine content. The above hypothesis also explains why only the cystine spectrum is observed although the cystine group is a small fraction of the total amino acid content of the protein. If the three-electron S▬S bond represents a lower energy state, the cystine is likely to donate an unpaired electron to any other ionized group formed by the irradiation. In this way, the two sulfur atoms of the cystine molecule act as an electron reservoir and supply electrons to fill vacancies at other points in the protein molecule, and such a mechanism should very much reduce the damage produced by the irradiation. It is therefore evident that in these particular cases, the electron resonance spectra have not only shown that the cystine type grouping is present in these proteins, but have also indicated that the breakdown process is transferred to the S▬S bond, and molecular fracture is therefore not so likely to take place in these compounds.
\n
These results indicate the type of reasoning that is used when deducing radiation effects from resonance spectra of complex molecules. Another example is given by the spectra observed from irradiated glycylglycine, silk, cattle hide and fish scale [43]. A symmetrical doublet with a frequency-independent splitting of 12 gauss is obtained in all of these cases. This is attributed to the direct dipole-dipole interaction between the hydrogen bonding proton and the unpaired electron localized on an oxygen atom of the adjacent polypeptide chain.
\n
This method of analysis by ‘correlation of similar spectra’ will have to be employed in most of the biological studies in the immediate future. The conclusions deduced in this way must be considered as tentative and often as just one possible explanation among several others. As further results are obtained, however, a greater background of information will be built up on the most likely type of hyperfine interaction present in any particular system.
\n
Gordy et al. [44, 45] have started a series of measurements on the electron resonance spectra observed from various X-irradiated proteins, to try and build up some systematic data for this purpose. With this in mind, the simpler peptide and polypeptides were studied first [44], so that their spectra could then be compared with those obtained from the more complex proteins. These investigations included X-irradiated glycylglycylglycine, DL-alanyl-DL-alanine, acetyl-DL-alanine, glycyl-DL-valine, acetyl-DL-leucine, and DL-alanylglycylglycine. The electron resonance spectra of the more complex proteins such as histone, insulin, hemoglobin and albumin were then investigated [45] and compared with those of the simpler proteins. It was found that two types of pattern were obtained in each case. One of these is very similar to that obtained from the irradiated cystine, and the other is a doublet similar to that obtained from the irradiated glycylglycine. It would therefore appear that the electron-donating power of the S-S bonds and the hydrogen bonding across the polypeptide chains may be general features in most protein structures. The work is also being extended to irradiated hormones and vitamins [44] such as progesterone parathyroid, vitamin A, vitamin K, ascorbic acid and also to irradiated nucleic acids [45] such as DNA, RNA, adenosine, cytidine and inosine. These measurements are all of a preliminary nature at the moment, and much careful and systematic work will have to be done before any definite conclusions can be established. The field is a very wide one, however, and when sufficient systematic measurements have been made, some detailed information on the different mechanisms associated with irradiation damage should emerge.
\n
Free radical reactions in a biological system are controlled by both pH and antioxidants. The effect of antioxidants on radiation damage in the biological system is a known fact. Contrary to this effect, it is formed by sensitizers, which are good oxidants. The best examples are O2 and quinones. In addition, various organic compounds can form active free radicals after reduction. An experiment showing free radical production as a secondary process in radiation damage can be summarized as follows: water and a mixture of 3% alcohol-riboflavin were reduced to 10−5 M riboflavin by ethyl alcohol radicals, resulting from OH and H radicals generated by 650 kV X-rays. This experiment was performed by Gordy et al. [43]. Information on the level of antioxidant can be obtained by titrating against a standard free radical solution and using EPR. Quantitative determinations of reduced free radical and therefore antioxidant concentrations are described by Blois et al. [46]. At this point, it is necessary to make more detailed studies on the clinical applications of EPR. EPR spectroscopy allows the observation of free radical intermediates in vivo. Commoner et al. [1] performed the first experiments with lyophilized samples. EPR studies were carried out for samples such as yeast, blood, rabbit organs, germinated digitalis seeds and barley leaves [47]. In the EPR spectrum of whole human blood, partial conversion of hemoglobin to methemoglobin was observed, and physical damage to both molecules was observed by lyophilization. In addition, a free radical signal associated with the breakdown of porphyrin ring structures of hemoglobin was recorded.
\n
Electron paramagnetic resonance (EPR) spectroscopy is the most reliable technique for relationship between reactive oxygen species and disease (or aging), the measurement of biological free radicals and redox states. It has been used in vitro to measure oxygen radicals such as hydroxyl radical and superoxide anion radical in combination with the spin-trapping technique [48]. The measurement of EPR is nondestructive and is unaffected by the turbidity of the sample, so people are interested in using EPR for the in vivo measurement of biological radicals. However, there are difficulties with this. First, steady concentrations of biological radicals are too low to detect directly with EPR spectroscopy during their very short half-life. Second, water in the body of the animal causes dielectric loss of the electromagnetic waves used for EPR measurement [49].
\n
EPR spectra of some biological samples are shown in Figure 3 [50] and Figure 4 [51].
\n
Figure 3.
EPR spectrum of whole blood of healthy person contains the signals from Cu2+ in ceruloplasmin (g = 2.05), high spin Fe3+ in transferrin (g = 4.14), high spin Fe3+ in methemoglobin (g = 5.85), low-spin ferriheme complex (g = 2.21) and cytochrome (g = 3.03). Spectrum recorded at 170 K.
\n
Figure 4.
EPR spectrum of the γ-irradiated single crystal of 2-thiothymine.
\n
\n
\n
7. Conclusion
\n
Free radicals play a role in biological oxidation-reduction reactions, radiation damage, photosynthesis and carcinogenesis. Electron paramagnetic resonance is a very good technique to directly observe free radical intermediates in most of these reactions. In particular, there are many environmental factors that affect human life. It is inevitable that this technique is guiding in discussing the effects of these factors and taking various measures accordingly.
\n
\n\n',keywords:"electron paramagnetic resonance (EPR), free radical, paramagnetic ion, oxidation, organic molecule, enzymatic dehydrogenation, carcinogenic agent",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/62327.pdf",chapterXML:"https://mts.intechopen.com/source/xml/62327.xml",downloadPdfUrl:"/chapter/pdf-download/62327",previewPdfUrl:"/chapter/pdf-preview/62327",totalDownloads:942,totalViews:133,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:34,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"February 26th 2018",dateReviewed:"June 4th 2018",datePrePublished:"November 5th 2018",datePublished:"February 13th 2019",dateFinished:"June 27th 2018",readingETA:"0",abstract:"Free radicals may participate in biological processes. An enzymatic dehydrogenation involved free radical intermediates. The oxidations of organic molecules, although they are bivalent, proceed in two successive steps, the intermediate state being a free radical. In an attempt to correlate the action of such a variety of carcinogenic agents as sodium hydroxide, ultraviolet and ionizing radiations and thousands of organic compounds, a free radical intermediate always suggests itself. Electron paramagnetic resonance (EPR) has brought sufficient sensitivity and discrimination to observe free radical intermediates directly in many of these reactions. EPR is aided by an increased sensitivity in many cases and has made a much greater contribution by distinguishing among paramagnetic ions, odd molecules and free radicals.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/62327",risUrl:"/chapter/ris/62327",book:{id:"7330",slug:"topics-from-epr-research"},signatures:"Betül Çalişkan and Ali Cengiz Çalişkan",authors:[{id:"199110",title:"Dr.",name:"Betül",middleName:null,surname:"Çalişkan",fullName:"Betül Çalişkan",slug:"betul-caliskan",email:"bcaliska@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199110/images/system/199110.jpg",institution:{name:"Pamukkale University",institutionURL:null,country:{name:"Turkey"}}},{id:"208732",title:"Dr.",name:"Ali Cengiz",middleName:null,surname:"Çalişkan",fullName:"Ali Cengiz Çalişkan",slug:"ali-cengiz-caliskan",email:"alicengizcaliskan@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The EPR study of free radicals in living tissue",level:"1"},{id:"sec_3",title:"3. EPR study of free radicals and carcinogenic activity",level:"1"},{id:"sec_4",title:"4. EPR study of oxidation: reduction and enzyme systems",level:"1"},{id:"sec_5",title:"5. EPR studies on photosynthesis and optical absorption",level:"1"},{id:"sec_6",title:"6. EPR study of X-irradiation of biological material",level:"1"},{id:"sec_7",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Commoner B, Townsend J, Pake GE. Free radicals in biological materials. Nature. 1954;174:689-691. DOI: 10.1038/174689a0\n'},{id:"B2",body:'McIlwain H. The magnitude of microbial reactions involving vitamin-like compounds. Nature. 1946;158(4025):898-902\n'},{id:"B3",body:'Blum HF. Light and the melanin pigment of human skin. Annals of the New York Academy of Sciences. 1948;4:388-398\n'},{id:"B4",body:'Kensler CJ, Dexter SO, Rhoads CP. 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Proceedings of the National Academy of Sciences of the United States of America. 1936;22(3):159-163. DOI: 10.1073/pnas.22.3.159\n'},{id:"B26",body:'Adams M, Blois MS Jr, Sands RH. Paramagnetic resonance spectra of some semiquinone free radicals. The Journal of Chemical Physics. 1958;28(5):774-776. DOI: 10.1063/1.1744269\n'},{id:"B27",body:'Beinert H. Evidence for an intermediate in the oxidation-reduction of flavoproteins. The Journal of Biological Chemistry. 1957;225(1):465-478\n'},{id:"B28",body:'Commoner B, Lippincott BB, Passonneau JV. Electron-spin resonance studies of free-radical intermediates in oxidation-reduction enzyme systems. Proceedings of the National Academy of Sciences of the United States of America. 1958;44(11):1099-1110\n'},{id:"B29",body:'Ehrenberg A, Ludwig GD. Free radical formation in reaction between old yellow enzyme and reduced triphosphopyridine nucleotide. Science. 1958;127(3307):1177-1178\n'},{id:"B30",body:'Bray RC, Malmström BG, Vänngård T. The chemistry of xanthine oxidase. 5. Electron-spin resonance of xanthine oxidase solutions. The Biochemical Journal. 1959;73(1):193-197\n'},{id:"B31",body:'Malmstrom BG, Vanngard T, Larsson M. An electron-spin-resonance study of the interaction of manganous ions with enolase and its substrate. Biochimica et Biophysica Acta. 1958;30(1):1-5\n'},{id:"B32",body:'Malmstrom BG, Mosbach R, Vanngard T. An electron spin resonance study of the state of copper in fungal laccase. Nature. 1959;183(4657):321-322\n'},{id:"B33",body:'Sands RH, Beinert H. On the function of copper in cytochrome oxidase. Biochemicaland Biophysical Research Communications. 1959;1(4):175-178. DOI: 10.1016/0006-291X(59)90013-0\n'},{id:"B34",body:'Beinert H, Sands RH. On the function of iron in DPNH cytochrome c reductase. Biochemical and Biophysical Research Communications. 1959;1(4):171-174. DOI: 10.1016/0006-291X(59)90012-9\n'},{id:"B35",body:'Hill R, Whittingham CP. Photosynthesis. London: Methuen; 1955\n'},{id:"B36",body:'Commoner B, Heise JJ, Townsend J. Light-induced paramagnetism in chloroplasts. Proceedings of the National Academy of Sciences of the United States of America. 1956;42(10):710-718\n'},{id:"B37",body:'Sogo PB, Pon NG, Calvin M. Photo spin resonance in chlorophyll-containing plant material. Proceedings of the National Academy of Sciences of the United States of America. 1957;43(5):387-393\n'},{id:"B38",body:'Tollin G, Calvin M. The luminescence of chlorophyll-containing plant material. Proceedings of the National Academy of Sciences of the United States of America. 1957;43(10):895-908\n'},{id:"B39",body:'Bradley DF, Calvin M. The effect of thioctic acid on the quantum efficiency of the hill reaction in intermittent light. Proceedings of the National Academy of Sciences of the United States of America. 1955;41(8):563-571\n'},{id:"B40",body:'Arnold W, Sherwood HK. Are chloroplasts semiconductors? Proceedings of the National Academy of Sciences of the United States of America. 1957;43(1):105-114\n'},{id:"B41",body:'Calvin M, Sogo PB. Primary quantum conversion process in photosynthesis: Electron spin resonance. Science. 1957;125(3246):499-500. DOI: 10.1126/science.125.3246.499\n'},{id:"B42",body:'Ingram DJE, Symons MCR. Solutions of Sulphur in oleum. Part I. Electron-spin resonance of solutions of Sulphur in oleum. Journal of the Chemical Society. 1957:2437-2439. DOI: 10.1039/JR9570002437\n'},{id:"B43",body:'Gordy W, Ard WB, Shields H. Microwave spectroscopy of biological substances. I. Paramagnetic resonance in X-irradiated amino acids and proteins. Proceedings of the National Academy of Sciences of the United States of America. 1955;41(11):983-996. DOI: 10.1073/pnas.41.11.983\n'},{id:"B44",body:'Rexroad HN, Gordy W. Electron-spin resonance studies of radiation damage to certain lipids, hormones, and vitamins. Proceedings of the National Academy of Sciences of the United States of America. 1959;45(2):256-269\n'},{id:"B45",body:'Shields H, Gordy W. Electron-spin resonance studies of radiation damage to the nucleic acids and their constituents. Proceedings of the National Academy of Sciences of the United States of America. 1959;45(2):269-281\n'},{id:"B46",body:'Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958;181:1199-1200. DOI: 10.1038/1811199a0\n'},{id:"B47",body:'Sands RH, Weaver HE, Franken PA. Paramagnetic ions in blood sera. In: Proceedings First Annual Conference of the Biophysical Society. Columbus, Ohio; 1958\n'},{id:"B48",body:'Buettner GR. Spin trapping: ESR parameters of spin adducts. Free Radical Biology & Medicine. 1987;3(4):259-303. DOI: 10.1016/S0891-5849(87)80033-3\n'},{id:"B49",body:'Takeshita K, Ozawa T. Recent progress in in vivo ESR spectroscopy. Journal of Radiation Research. 2004;45(3):373-384. DOI: 10.1269/jrr.45.373\n'},{id:"B50",body:'Kubiak T, Krzyminiewski R, Dobosz B. EPR study of paramagnetic centers in human blood. Current Topics in Biophysics. 2013;36(1):7-13. DOI: 10.2478/ctb-2013-0006\n'},{id:"B51",body:'Bešić E, Gomzi V. EPR study of a sulfur-centered π radical in γ-irradiated single crystal of 2-thiothymine. Journal of Molecular Structure. 2008;876(1-3):234-239. DOI: 10.1016/j.molstruc.2007.06.033\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Betül Çalişkan",address:"bcaliska@gmail.com",affiliation:'
Department of Physics, Faculty of Arts and Science, Pamukkale University, Turkey
Department of Chemistry, Faculty of Science, Gazi University, Turkey
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1. Introduction
Infections caused by a variety of bacterial, fungal, viral, and other infectious microorganisms are considered to be the world’s most leading problem. Infectious diseases are considered to be the world most leading cause of death, with almost 50,000 deaths per day [1]. Bacterial and fungal infections are the major cause of morbidity and mortality in both developed and developing countries [2]. Staphylococcus aureus is a gram-positive, coagulase-positive opportunistic bacterial pathogen, commonly found in the human nasal mucosa in the approximately 20–40% population [3, 4]. It causes a wide range of infections such as skin infections, including abscesses, impetigo, and necrotizing fasciitis; tissue infections, including osteomyelitis and endocarditis; and toxicities, including toxic shock syndrome, pneumonia, sepsis, and surgical site infections [5, 6, 7]. The superficial and invasive infections caused by S. aureus continue to raise serious health challenges globally as it notoriously exhibits resistance [8, 9]. These infections have rapidly developed resistance against most of the available antimicrobials, which pose serious threats [10, 11, 12, 13]. Infections caused by S. aureus are associated with significantly higher mortality, because of the limitations of available antimicrobial therapies, difficulties in making a rapid and accurate diagnosis, and the development of multidrug resistance (MDR) [14]. The acute and chronic staphylococcal infections have now become more problematic after emerging multidrug resistance (MDR) against various frontline antibiotics [15, 16]. Antibiotics are small molecules that selectively inhibit the growth of a plethora of bacterial and other infections. These heterogeneous group molecules continue to be save many lives from different bacterial infections. Antibiotics are either naturally synthesized by microorganisms or chemically modified into exciting drugs. β-lactam antibiotics (β-LA) are considered to be the most successful and frequently used antibiotics against a number of bacterial infections. The underlying reason behind this is their wide spectrum activity, oral availability, excellent pharmacokinetics, lack of toxicity, and bactericidal action [17]. Due to the widespread and prolonged practice of β-LA emerged resistance to these resort and became an alarming and emerging problem to the public health. The microbial pathogens tend to adopt different resistance mechanism to skip the cytotoxic effect of β-LA. The progression in β-LA drug resistance to emerge multiple antibiotic-resistant microorganisms has made it difficult to manage many infectious diseases using common anti-infective drugs. In this chapter, we focus on emerging trends of drug resistance in S. aureus to the different β-LA.
2. β-Lactam antibiotics (β-LA)
The landmark discovery the beta-lactam penicillin has been developed with the remarkable weapon to control bacterial infections during the Second World War [18]. It was naturally synthesized from Penicillium chrysogenum (also known as Penicillium notatum). Penicillin G was the first β-lactam antibiotic (β-LA) discovered in 1944, which began the era of antibiotics against a wide range of infectious microorganisms [19]. The development of penicillin led to search its different derivatives (amoxicillin and methicillin) for the betterment of their efficacy, bioavailability, solubility, stability, and other pharmacokinetic properties and to evade steadily emerging problem of multidrug resistance (MDR). Structurally, penicillin is composed of a thiazolidine ring attached to a side chain of a four-membered beta-lactam ring. All penicillins are derivatives of 6-aminopenecillinic acid, which sometimes differ in their side-chain structure. Many β-LA have lactam ring as an integral part of a molecule such as cephalosporins, monobactams, cephamycins, and the carbapenems (imipenem and meropenem). These β-LA antibiotics came into the light to rescue mankind from different Gram –ve and Gram +ve bacterial infections including S. aureus. β-LA are the most available and over 34 β-LA approved by the FDA, which together constitute ~50% of all antibiotic prescriptions worldwide. Now, β-LA share the annual consumption of over $15 billion, which contribute almost 65% of the total antibiotics [20].
The β-LA primarily target the cell wall of a bacterial pathogen. Peptidoglycan or murien present in the cell wall provides the mechanical strength to the bacterial cell membrane, which is composed of an alternating unit of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) residues, joined together by β-1 → 4 linkage. The NAM is further linked with a pentapeptide stem, which is composed of L-Ala-D-Glu- L-Lys-D-Ala-D-Ala. The order and type of amino acids are almost similar in Gram –ve and Gram +ve bacterial with some slight variations. The last D-Ala is lost during maturation and glycan assembly is cross-linked to form a bridge with the carboxyl group of D-Ala at position 4 and the amino group of the amino acid at position 3. Mechanistically, β-LA acts upon a 4-membered “beta-lactam” ring, which shows a resemblance to D-Ala-D-Ala sequence of the cell wall [21]. The primary function of PBP is in the elongation of the cell wall, which is composed of two distinct components termed as PBP1–4. The radioactive analysis revealed that penicillin specifically interacts with PBP protein via covalent interactions [22]. The tight binding of β-LA to the transpeptidase domain of PBP (penicillin-binding protein) thereby inhibits the peptidoglycan synthesis by acylating transpeptidase, involved in crosslinking peptide to form peptidoglycan [23].
3. β-Lactam resistance in S. aureus
According to the European Centre for Diseases Control (ECDC), antimicrobial resistance is the single biggest threat facing the world in the area of infectious diseases. With the progression of antibiotics discoveries and their prophylactic usages have emerged drug resistance to single or multiple drugs. Antibiotic resistance is a natural selection process when microorganisms are treated with different antibiotics, and microorganisms tend to escape this selection pressure with greater competency to survive and thus show antibiotics resistance. In contrast, bacteria with a susceptible nature are killed with exposed antibiotics. Emerging resistance to β-LA is a serious health concern that causes a major hurdle in the treatment of bacterial infections. The condition of drug resistance is primarily developed by increasing and indiscriminate usage of antibiotics in clinical ailments, unregulated sales of antibiotics, a long course of medication, and poor public health infrastructure. According to a hospital survey, over 80% of clinical samples of S. aureus were established resistance to the frontline antibiotics including methicillin [24, 25]. It has been reported that 70% of nosocomial bacterial pathogens have emerged resistance to more than one antibiotic during medication of chronic infections. In contrast, an alarming increase in resistance of community-acquired bacteria has also been observed with significant high rate both in acute and chronic bacterial infections. The emergence of drug-resistant strains of Gram-positive (Staphylococcus, Enterococcus, Streptococcus sp) and Gram-negative (Pseudomonas, Klebsiella, Enterobacter, Acinetobacter, Salmonella sp) bacteria is the more serious in the present therapeutic scenario. S. aureus clearly represents one of the most challenging pathogenic bacteria. Resistance in S. aureus strains has been continuously increasing; thus, the ability of these pathogens to spread in both hospital and community settings increased. Bacteria remarkably developed resistant to antimicrobial drugs in several ways. Upon antibiotics treatment, bacteria tend to overcome the selection pressure of the drug by morphological and genetic alterations or drug inactivation. Alterations of membrane integrity and transfer of resistance genes from one strain to another are the common examples of β-LA-mediated resistance in S. aureus. β-LA, Penicillin was initially succeeded in the treatment of S. aureus infections but widespread and prolonged uses of penicillin were no longer be effective and resistance has been emerged soon after in the 1950s [19]. Antibiotic resistance can be a typical feature of a bacterial species (intrinsic resistance) or acquired by the individual organism that is naturally susceptible (acquired resistance). The acquired resistance is the consequence of chromosomal mutations or acquisition of resistance genes by horizontal gene transfer [26]. Resistance to multiple β-LA can be acquired by individual strains, resulting in multidrug-resistant phenotypes. The high prevalence of drug resistance is primarily adopted by unregulated sales of antibiotics without prescription, a long course of medication, indiscriminate usage of drugs, and poor health infrastructure. The mobility and mortality caused by drug resistance in public health are difficult to evaluate. In 2013, Center for Disease Control and Prevention (CDC) reported more than 11,000 deaths in the USA had a methicillin-resistant S. aureus (MRSA)-related infection (CDC 2013). This represents almost 50% of all causalities caused by antibiotic-resistant bacteria. As per WHO report, the MRSA remains among the high-priority multidrug-resistant organisms that need renewed efforts for the research and development of new antibiotics and innovative preventive approaches.
4. Mechanism of β-lactam resistance in S. aureus
Different mechanisms of drug resistance in bacterial pathogens are the major hurdle in their treatment. With emerging resistance, it became a serious concern to look into drug resistance mechanism, which can help us to prescribe a specific medication to effectively overcome the problem of resistance.
Several biochemical mechanisms are responsible for β-LA resistance, including enzymatic (β-lactamase) production inactivation of the drug (drug inactivation), modifications of drug target in penicillin-binding protein (PBPs) (target modifications), limiting uptake of drug by biofilm formation (reduced drug uptake), and active efflux of the drug (drug efflux) as shown in Figure 1 [27, 28]. Bacterial pathogens resist the inhibitory action of antibiotics primarily due to the presence of an enzyme that inactivates the antibiotic or modified antibiotic target by mutation or by the post-translational mechanism, which reduces binding of the antibiotic to the target or bypass of the function dependent on the antibiotic target by an alternative enzyme that is not inhibited by the antibiotic. Moreover, overexpression of drug efflux pumps rendered to reduce uptake of the antibiotic inside the cell, by pumping out the antibiotics from the cell. In contrast, encapsulation of biofilm over the cell boundary reduces the cell permeability to resist antibiotics entry into the cell. The expression of chromosomal β-lactamase can be induced by either producing the plasmid-encoded penicillinase (β-lactamase) enzyme that hydrolyzes β-lactam ring or expression of PBP2a, and a penicillin-binding protein (PBP) encoded by gene mecA spread through horizontal gene transfer with low affinity to β-lactam antibiotics is primarily responsible for penicillin resistance [17]. The penicillin-binding cascade induces the blaZ-encoded penicillinase in S. aureus, which is transcriptionally regulated by regulatory genes blaI and blaR1 [26, 29].
Figure 1.
β-Lactam resistance mechanism of S. aureus.
5. Methicillin resistance in S. aureus
Methicillin was introduced in clinical practice for the effective treatment of penicillin-resistant S. aureus infections [30]. After 2 years, the second wave of resistance against methicillin came into the light and the first report on methicillin resistance S. aureus (MRSA) strain was published by MP Jevons in 1961 [31]. Statistically, incidences of methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant S. aureus (VRSA) infections have increased up to 54% in both hospital-acquired (HA) and community-acquired (CA) [32]. These antimicrobial-resistant infections cause a significant economic burden on public health. The economic burden of antibiotic resistance in Europe was estimated at almost 1.5 billion euros. However, USA spent more than 55 billion dollars each year on the treatment of antibiotic-resistant infections [9]. It was found that acquisition of methicillin resistance in S. aureus was primarily contributed by the integration of a mecA gene encoded for low-affinity penicillin-binding protein 2a or 2′ (PBP2a or PBP2′) into the staphylococcal chromosomal cassette (SCCmec) element of methicillin-sensitive S. aureus (MRSA) [33]. The expression of mecA in MRSA is induced by the interaction of methicillin and other antibiotics to the regulatory network. MecIR a regulatory protein, homologous to the BlaIR proteins, controls the expression of mecA. It is under the control of MecIR regulatory proteins that are homologous to the BlaIR proteins that regulate BlaZ expression [34, 35]. The SSCmec is located specifically with an unknown gene (orfX) of the staphylococcal chromosomal. The function of the unknown gene is mediated by two recombinases termed as ccrA and ccrB that help in the site-specific integration or excision of DNA elements from the staphylococcal chromosomal [36, 37]. The insertion sequence, transposon (Tn554) or erythromycin- and spectinomycin-encoded resistance genes, and tobramycin and kanamycin resistance-encoded pUB110 plasmid can be additionally jumped in the SSCmec region. Typing of SSCmec elements is fundamental for the molecular epidemiology of MRSA and categorized majorly into five types, that is, type I-V [38]. The SSCmec-type I-III elements are present in hospital-acquired MRSA strains, which are typically resistant to non-β-lactam antibiotics. In contrast, SSCmec-type IV-V are only resistance to methicillin, which are primarily present in community-acquired MRSA (CA-MRSA). Different studies revealed that multiple insertions of SCCmec elements in the staphylococcal chromosome of MSSA strains yield a MRSA lineage. The mecC gene, homolog to mecA gene, exhibits 68.7% nucleotide identity is identified in S. aureus, Staphylococcus sciuri, and Staphylococcus xylosus strains [39]. The recent studies revealed that mecC carrying S. aureus contributes in methicillin resistance in the human population by up to 2.8% of MRSA strains [40, 41, 42], while no report was found on mecB-carrying S. aureus resistance to methicillin. In many MRSA strains, the expression of mecA is also affected either by the synthesis of truncated MecIR regulatory proteins or by repression by β-lactamase regulators BlaI and BlaR. The Mec and Bla regulatory proteins can alter the functional behavior and expression of PBP2a-encoded gene in MRSA strains. In a short period, MRSA strains have been identified all around the globe particularly Asia, USA, and Europe [43]. In spite of the rapidly spreading of methicillin resistance, MRSA exhibited broad-spectrum drug resistance against methicillin, penicillins, cephalosporins, and carbapenems. The MRSA cases were increased in hospitals and other healthcare facilities (hospital-acquired), and in communities (community-acquired infections). People with immediate surgeries or stay in healthcare facilities are at MRSA higher risk. Infection also spreads if a medical device has been put in their body or when they come close to contact with MRSA-infected patient. MRSA spreads in communities through uncovered or draining wounds mostly associated with crowded living, sharing personal items, recent stays in healthcare facilities, etc. In 2017, CDC reported that more than a 0.3 million cases and over 10,000 deaths from MRSA-related infections are estimated in-hospital patients with more than 1.7 billion healthcare burdens in the United States. This figure represents mere a 50% of all the mortalities caused by antibiotic-resistant bacteria. The prevalence of MRSA infections in India has been reported to increase from 29% in 2009 to 47% in 2014 [35].
6. Cephalosporin resistance in S. aureus
Similar to penicillin or other β-lactams, cephalosporins also target to bind penicillin-binding proteins (PBPs) to inhibit peptidoglycan formation in bacteria. These are effectively used in the treatment of superficial (skin and soft tissue) infections, and nosocomial and community-acquired pneumonia. Different strains of S. aureus strains have evolved resistance to cephalosporins, which evolved by reducing the binding affinity of cephalosporins to transpeptidase of PBPs, and also, β-lactamases are produced by bacteria having encoded plasmid for inactivation of therapeutics effect of cephalosporins. The plasmid-mediated β-lactamase resistance is corroborated by the amount and activity of the enzyme produced in bacteria.
Recent studies revealed that the prevalence of cephalosporins resistance in S. aureus is comparable to the β-lactamase-resistant penicillin, which accounts for 30–35% [44, 45]. Ceftaroline is the fifth-generation antibiotics, approved by the FDA in 2010, which has a broad-spectrum activity against a plethora of bacterial pathogens. Ceftaroline is active against methicillin-resistant S. aureus (MRSA) and has been successfully used for the treatment of different invasive bacterial infections with low adverse effects. This potent third-generation drug was found resistance in MRSA-ST293 strain in different geographical regions. Ceftaroline had the higher affinity to PBP but nonsense or missense mutations in the mecA gene alter the amino acid sequence of PBP protein, which causes alteration in the ceftaroline binding to PBPs. In addition, alteration of the promoter sequence of PBP4 by mutation increases PBP4 production that leads to resistance to ceftaroline [46].
7. Carbapenem-resistance
The β-lactam antibiotic carbapenems are the last resort, potent, broad-spectrum antibiotic against Gram +ve and Gram –ve bacterial pathogens. They contain a carbapenem structure linked together with a beta-lactam ring, which primarily targets to bind with PBPs of the cell wall. Due to high potency, low adverse effect appeals to prefer the use of carbapenems. Prolonged and widespread uses of the drug have developed carbapenems resistance, which is contributed by a different mechanism. The resistance that arises to carbapenems is due to β-lactamase gene transfer/production, mutational alteration in PBPs, and expression of efflux pump systems [47, 48]. The carbapenem resistance is mainly contributed by β-lactamase production.
8. Future perspective
Emerging resistance in S. aureus is a serious human health problem, which continuously increasing mortality and morbidity rates in both nosocomial and acquired infections. The constant evolution of resistance to topical antibiotics including the continuing appearance of new resistance mechanisms and complexity in multidrug-resistant phenotypes are appealing to find new diagnostic tools and therapeutic strategies to get rid of this problem. However, a lot of toiling has continued to devise a workable treatment against staphylococcal infections particularly for the elimination of MRSA and VRSA pathogens. Emerging MDR in S. aureus has evolved major challenges in research and need to expend research to the next level to understand the progression of drug resistance pathways and infections pattern of S. aureus. The new search of therapeutics targets and bioactive molecules and their judicious use may be proven significantly to prevent the problem of drug resistance [2, 49]. Reducing the outer membrane permeability of bacterial cells can circumvent the problem of drug resistance. Iron conjugated with the antibiotic method may help to selectively interact to the outer membrane to active transport of antibiotic inside the cell [50]. Another possible approach has been targeted to inhibit quorum sensing that is primarily related to the virulence factors release and associated with the microbial pathogenesis. Chemically, virulence factors are toxic to the host cells that disrupt immune response, along with host cell disruption and cell adhesion. SarA and agr are two main quorum sensing mechanisms of S. aureus, which can be targeted to block the quorum sensing for controlling S. aureus infections. In addition, bacteriophage therapy is one of the potential methods for controlling the drug resistance in S. aureus infection. Phage therapy has many advantages over chemotherapy, for example, very specific, no side effect, environmental friendly, no allergenic effects, and harmless to the eukaryotic host [51]. Phage has been used to eliminate MRSA infections but is still immature in clinical application [51]. The phage-based treatment of resistant S. aureus will further be helpful to select the gene responsible for its control. These strategies will pave a way to develop a vaccine in future against the S. aureus.
9. Conclusion
It is very clear that bacterium including Staphylococcus aureus shows extraordinary adaptability to cope with antibiotic effect and emerge drug resistance against antibiotics. The phenomenon of drug resistance was first observed when β-lactam antibiotics became ineffective after indiscriminative uses and plasmid-responsive β-lactamase (penicillinase) synthesis. The second wave of resistance against methicillin has been primarily contributed by the stable integration of a mecA gene-encoded penicillin-binding protein and penicillin-binding protein 2a or 2′ (PBP2a or PBP2′) into the staphylococcal chromosomal cassette (SCCmec) element. Cephalosporins have been proven as an effective drug preventing MRSA infections but failed. In progression to antibiotics, carbapenems have been used for preventing S. aureus infections, but multidrug resistance (MDR) strains developed. The common cause of bacterial resistance involves horizontal gene transfer, target alteration by point mutations, and expression of efflux pump, which made a variety of antibiotics ineffective and induces persistent infections in both hospital and community settings. Moreover, the prolonged and widespread use of different antibiotics, lack of awareness, and insanitation, primarily contribute in rapidly developing multiple drug resistance (MDR) in developing countries that causes a major financial burden in the treatment of infectious diseases. Though a lot of toiling is involved in devising an effective treatment against staphylococcal infections particularly for the elimination of MRSA and VRSA, the new search of bioactive molecules and their judicious use may be proven significantly to prevent the problem of drug resistance.
\n',keywords:"Staphylococcus aureus, Drug resistance, β-lactam antibiotics, Penicillin, Methicillin, Cephalosporin",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/79032.pdf",chapterXML:"https://mts.intechopen.com/source/xml/79032.xml",downloadPdfUrl:"/chapter/pdf-download/79032",previewPdfUrl:"/chapter/pdf-preview/79032",totalDownloads:152,totalViews:0,totalCrossrefCites:0,dateSubmitted:"March 5th 2021",dateReviewed:"September 24th 2021",datePrePublished:"October 18th 2021",datePublished:"December 8th 2021",dateFinished:"October 18th 2021",readingETA:"0",abstract:"Staphylococcus aureus is a notorious human pathogen that causes superficial and invasive infections both in nosocomial and community-acquired settings. The prevalence of staphylococcal infections became more challenging after emerging resistance against topical antibiotics. S. aureus evolved resistance to β-lactam antibiotics due to modification and expression of penicillin-binding proteins (PBP), inactivation of drug by β-lactamase synthesis, limiting uptake of drug by biofilm formation, and reducing uptake by expression of efflux pump. The wave of resistance was first observed in penicillin by β-lactamase production and PBPs modification. The second wave of resistance emerged to methicillin by appearing methicillin-resistant S. aureus (MRSA) strains. Cephalosporin has long been used as the last resort for preventing MRSA infections, but resistant strains appeared during treatment. In progression to control MRSA or related infections, carbapenems have been used but strains developed resistance. S. aureus is among the high-priority resistance organisms that need renewed efforts for the research and development of new antibiotics and innovative preventive approaches. However, a lot of toiling is involved in devising an effective treatment against drug resistant S. aureus. This chapter aim is to retrospectively determine the progression of resistance in S. aureus, against different β-lactam antibiotics and their challenges of medication.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/79032",risUrl:"/chapter/ris/79032",signatures:"Antresh Kumar and Manisha Kaushal",book:{id:"9525",type:"book",title:"Insights Into Drug Resistance in Staphylococcus aureus",subtitle:null,fullTitle:"Insights Into Drug Resistance in Staphylococcus aureus",slug:"insights-into-drug-resistance-in-staphylococcus-aureus",publishedDate:"December 8th 2021",bookSignature:"Amjad Aqib",coverURL:"https://cdn.intechopen.com/books/images_new/9525.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-743-9",printIsbn:"978-1-83962-742-2",pdfIsbn:"978-1-83962-744-6",isAvailableForWebshopOrdering:!0,editors:[{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"333046",title:"Associate Prof.",name:"Antresh",middleName:null,surname:"Kumar",fullName:"Antresh Kumar",slug:"antresh-kumar",email:"antreshkumar@cuh.ac.in",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"439834",title:"Dr.",name:"Manisha",middleName:null,surname:"Kaushal",fullName:"Manisha Kaushal",slug:"manisha-kaushal",email:"manishakaushal1980@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. β-Lactam antibiotics (β-LA)",level:"1"},{id:"sec_3",title:"3. β-Lactam resistance in S. aureus",level:"1"},{id:"sec_4",title:"4. Mechanism of β-lactam resistance in S. aureus",level:"1"},{id:"sec_5",title:"5. Methicillin resistance in S. aureus",level:"1"},{id:"sec_6",title:"6. Cephalosporin resistance in S. aureus",level:"1"},{id:"sec_7",title:"7. Carbapenem-resistance",level:"1"},{id:"sec_8",title:"8. Future perspective",level:"1"},{id:"sec_9",title:"9. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Holmes KK, Bertozzi S, Bloom BR, Prabhat Jha P, Gelband H, DeMaria LM, et al. Major infectious diseases: Key messages from disease control priorities. In: Holmes KK, Bertozzi S, Bloom BR, Jha P, editors. Major Infectious Diseases. 3rd ed. Washington (DC): The International Bank for Reconstruction and Development/The World Bank; 2017'},{id:"B2",body:'Kumar S, Kumar A, Kaushal M, Kumar P, Mukhopadhyay K, Kumar A. 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Ko"}]},{id:"68705",doi:"10.5772/intechopen.88239",title:"Voice Identification Using Classification Algorithms",slug:"voice-identification-using-classification-algorithms",totalDownloads:1073,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"This article discusses the classification algorithms for the problem of personality identification by voice using machine learning methods. We used the MFCC algorithm in the speech preprocessing process. To solve the problem, a comparative analysis of five classification algorithms was carried out. In the first experiment, the support vector method was determined—0.90 and multilayer perceptron—0.83, that showed the best results. In the second experiment, a multilayer perceptron with an accuracy of 0.93 was proposed using the Robust scaler method for personal identification. Therefore, to solve this problem, it is possible to use a multi-layer perceptron, taking into account the specifics of the speech signal.",book:{id:"9384",slug:"intelligent-system-and-computing",title:"Intelligent System and Computing",fullTitle:"Intelligent System and Computing"},signatures:"Orken Mamyrbayev, Nurbapa Mekebayev, Mussa Turdalyuly, Nurzhamal Oshanova, Tolga Ihsan Medeni and Aigerim Yessentay",authors:[{id:"308920",title:"Prof.",name:"Orken",middleName:null,surname:"Mamyrbayev",slug:"orken-mamyrbayev",fullName:"Orken Mamyrbayev"},{id:"308925",title:"MSc.",name:"Nurbapa",middleName:null,surname:"Mekebayev",slug:"nurbapa-mekebayev",fullName:"Nurbapa Mekebayev"},{id:"308927",title:"MSc.",name:"Mussa",middleName:null,surname:"Turdalyuly",slug:"mussa-turdalyuly",fullName:"Mussa Turdalyuly"},{id:"308928",title:"Dr.",name:"Nurzhamal",middleName:null,surname:"Oshanova",slug:"nurzhamal-oshanova",fullName:"Nurzhamal Oshanova"}]}],mostDownloadedChaptersLast30Days:[{id:"68705",title:"Voice Identification Using Classification Algorithms",slug:"voice-identification-using-classification-algorithms",totalDownloads:1075,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"This article discusses the classification algorithms for the problem of personality identification by voice using machine learning methods. We used the MFCC algorithm in the speech preprocessing process. To solve the problem, a comparative analysis of five classification algorithms was carried out. In the first experiment, the support vector method was determined—0.90 and multilayer perceptron—0.83, that showed the best results. In the second experiment, a multilayer perceptron with an accuracy of 0.93 was proposed using the Robust scaler method for personal identification. Therefore, to solve this problem, it is possible to use a multi-layer perceptron, taking into account the specifics of the speech signal.",book:{id:"9384",slug:"intelligent-system-and-computing",title:"Intelligent System and Computing",fullTitle:"Intelligent System and Computing"},signatures:"Orken Mamyrbayev, Nurbapa Mekebayev, Mussa Turdalyuly, Nurzhamal Oshanova, Tolga Ihsan Medeni and Aigerim Yessentay",authors:[{id:"308920",title:"Prof.",name:"Orken",middleName:null,surname:"Mamyrbayev",slug:"orken-mamyrbayev",fullName:"Orken Mamyrbayev"},{id:"308925",title:"MSc.",name:"Nurbapa",middleName:null,surname:"Mekebayev",slug:"nurbapa-mekebayev",fullName:"Nurbapa Mekebayev"},{id:"308927",title:"MSc.",name:"Mussa",middleName:null,surname:"Turdalyuly",slug:"mussa-turdalyuly",fullName:"Mussa Turdalyuly"},{id:"308928",title:"Dr.",name:"Nurzhamal",middleName:null,surname:"Oshanova",slug:"nurzhamal-oshanova",fullName:"Nurzhamal Oshanova"}]},{id:"70142",title:"Vehicle Tracking Using Video Surveillance",slug:"vehicle-tracking-using-video-surveillance",totalDownloads:1279,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"In numerous applications including the security of individual vehicles as well as public transportation frameworks, the ability to follow or track vehicles is very helpful. Using computer vision and deep learning algorithms, the project deals with the concept of vehicle tracking in real-time based on continuous video stream from a CCTV camera to track the vehicles. The tracking system is tracking by detection paradigm. YOLOv3 object detection is applied to achieve faster object detection for real-time tracking. By implementing and improving the ideas of Deep SORT tracking for better occlusion handling, a better tracking system suitable for real-time vehicle tracking is presented. So as to demonstrate the achievability and adequacy of the framework, this chapter presents exploratory consequences of the vehicle following framework and a few encounters on handy executions.",book:{id:"9384",slug:"intelligent-system-and-computing",title:"Intelligent System and Computing",fullTitle:"Intelligent System and Computing"},signatures:"Sandesh Shrestha",authors:[{id:"310485",title:"Mr.",name:"Sandesh",middleName:null,surname:"Shrestha",slug:"sandesh-shrestha",fullName:"Sandesh Shrestha"}]},{id:"69374",title:"The Novel Applications of Deep Reservoir Computing in Cyber-Security and Wireless Communication",slug:"the-novel-applications-of-deep-reservoir-computing-in-cyber-security-and-wireless-communication",totalDownloads:815,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"This chapter introduces the novel applications of deep reservoir computing (RC) systems in cyber-security and wireless communication. The RC systems are a new class of recurrent neural networks (RNNs). Traditional RNNs are very challenging to train due to vanishing/exploding gradients. However, the RC systems are easier to train and have shown similar or even better performances compared with traditional RNNs. It is very essential to study the spatio-temporal correlations in cyber-security and wireless communication domains. Therefore, RC models are good choices to explore the spatio-temporal correlations. In this chapter, we explore the applications and performance of delayed feedback reservoirs (DFRs), and echo state networks (ESNs) in the cyber-security of smart grids and symbol detection in MIMO-OFDM systems, respectively. DFRs and ESNs are two different types of RC models. We also introduce the spiking structure of DFRs as spiking artificial neural networks are more energy efficient and biologically plausible as well.",book:{id:"9384",slug:"intelligent-system-and-computing",title:"Intelligent System and Computing",fullTitle:"Intelligent System and Computing"},signatures:"Kian Hamedani, Zhou Zhou, Kangjun Bai and Lingjia Liu",authors:[{id:"245542",title:"Mr.",name:"Kangjun",middleName:null,surname:"Bai",slug:"kangjun-bai",fullName:"Kangjun Bai"},{id:"309770",title:"Ph.D. Student",name:"Kian",middleName:null,surname:"Hamedani",slug:"kian-hamedani",fullName:"Kian Hamedani"},{id:"310622",title:"Mr.",name:"Zhou",middleName:null,surname:"Zhou",slug:"zhou-zhou",fullName:"Zhou Zhou"},{id:"310623",title:"Prof.",name:"Lingjia",middleName:null,surname:"Liu",slug:"lingjia-liu",fullName:"Lingjia Liu"}]},{id:"69600",title:"Persuasion in Mobile Financial Service: A Case Study with a Bank Savings Mobile Application",slug:"persuasion-in-mobile-financial-service-a-case-study-with-a-bank-savings-mobile-application",totalDownloads:768,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Financial institutions are undergoing a technology transformation. The digitization now drives the addition of new services and expectations. In this context, mobile has become a strategic channel to encourage users to adopt specific behaviors and change habits effortlessly. The research question underlying this study focuses on mobile banking applications and how they could support the adoption of savings behaviors. A qualitative study was conducted, in order to evaluate the persuasiveness embedded in a mobile bank saving app. Three experts in human-computer interaction (HCI) assessed the mobile app interfaces through a scientific grid of persuasive criteria to guide their heuristic inspection. Results confirm both a satisfactory level of persuasiveness of the mobile app and the dynamic application of persuasive criteria. The study shows that a mobile app involving certain specific features supports a positive banking customer’s experience related to savings. This study contributes to the user experience field, showing that mobile apps can support behavioral change when persuasiveness is embedded in the design process. Using a valid and reliable assessment method to establish the level of persuasiveness of a bank savings mobile app, this study confirms that the persuasion grid is applicable to mobile interfaces.",book:{id:"9384",slug:"intelligent-system-and-computing",title:"Intelligent System and Computing",fullTitle:"Intelligent System and Computing"},signatures:"Prom Tep Sandrine, Ruer Perrine and Nemery Alexandra",authors:[{id:"308744",title:"Dr.",name:"Sandrine",middleName:null,surname:"Prom Tep",slug:"sandrine-prom-tep",fullName:"Sandrine Prom Tep"},{id:"308746",title:"Prof.",name:"Perrine",middleName:null,surname:"Ruer",slug:"perrine-ruer",fullName:"Perrine Ruer"},{id:"311806",title:"Dr.",name:"Alexandra",middleName:null,surname:"Nemery",slug:"alexandra-nemery",fullName:"Alexandra Nemery"}]},{id:"69265",title:"Wax Deposition in Crude Oil Transport Lines and Wax Estimation Methods",slug:"wax-deposition-in-crude-oil-transport-lines-and-wax-estimation-methods",totalDownloads:722,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Petroleum industry is one of the major industries serving the energy demands. Flow assurance is essential for providing continuous fuel supply. Wax deposition is the main issue that affects flow assurance or reduces the efficiency of transporting crude oil. As the maintenance cost of repairing and troubleshooting is very high, addressing issues related to flow assurance becomes critical in the petroleum industry. This chapter will explore methods used for reducing, cleaning, and monitoring deposition of wax. Wax dissolved in the crude oil gets crystallized causing accumulation across the pipe walls once the bulk temperature of the crude oil gets lower than wax appearance temperature (WAT). Mechanical, thermal, chemical, and microbial methods highlighting general practice in the industry are discussed in this chapter. Next, the direct techniques providing information about the numerical wax deposition models used along with scientific measurement techniques are emphasized. Later, the indirect measurement techniques are discussed providing information about the external probing and nondestructive techniques to obtain information about wax layer deposition inside the pipe. The role of artificial intelligence and use of fuzzy logic for effective wax prediction or in developing the existing wax numerical models are emphasized in the last section.",book:{id:"9384",slug:"intelligent-system-and-computing",title:"Intelligent System and Computing",fullTitle:"Intelligent System and Computing"},signatures:"Fadi Alnaimat, Mohammed Ziauddin and Bobby Mathew",authors:[{id:"151722",title:"Dr.",name:"Fadi",middleName:null,surname:"Alnaimat",slug:"fadi-alnaimat",fullName:"Fadi Alnaimat"},{id:"245338",title:"Dr.",name:"Bobby",middleName:null,surname:"Mathew",slug:"bobby-mathew",fullName:"Bobby Mathew"},{id:"307726",title:"MSc.",name:"Mohammed",middleName:null,surname:"Ziauddin",slug:"mohammed-ziauddin",fullName:"Mohammed Ziauddin"}]}],onlineFirstChaptersFilter:{topicId:"535",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:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,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:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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\r\n\t
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"April 24th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. Her publications cover a wide range of scientific and technical research publications that include edited books, book chapters, refereed journals, refereed conference papers and reports for local, state and federal government clients. She has also produced podcasts for various organisations and participated in media interviews. She has received state, national and international funding worth over USD $25 million. Usha has been awarded the Quarterly Franklin Membership by London Journals Press (UK). Her biography has been included in the Marquis Who's Who in the World® 2018, 2016 (33rd Edition), along with approximately 55,000 of the most accomplished men and women from around the world, including luminaries as U.N. Secretary-General Ban Ki-moon. In 2017, Usha was awarded the Marquis Who’s Who Lifetime Achiever Award.",institutionString:null,institution:{name:"RMIT University",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo is a Professor at the Department of Engineering of the University of Naples “Parthenope”, Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino. Her research interests include multi-criteria decision analysis, industrial plant, logistics, manufacturing and safety. She serves as an Associate Editor for the International Journal of the Analytic Hierarchy Process. She is a member of AHP Academy and a member of several editorial boards. 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Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. She holds a Ph.D. from the University of Oulu, Finland.',institutionString:"Swedish Association for Distance Education, Sweden",institution:null},editorTwo:null,editorThree:null},{id:"94",title:"Climate Change and Environmental Sustainability",coverUrl:"https://cdn.intechopen.com/series_topics/covers/94.jpg",isOpenForSubmission:!1,editor:null,editorTwo:null,editorThree:null},{id:"95",title:"Urban Planning and Environmental Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/95.jpg",isOpenForSubmission:!0,editor:{id:"181079",title:"Dr.",name:"Christoph",middleName:null,surname:"Lüthi",slug:"christoph-luthi",fullName:"Christoph Lüthi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHSqQAO/Profile_Picture_2022-04-12T15:51:33.png",biography:"Dr. Christoph Lüthi is an urban infrastructure planner with over 25 years of experience in planning and design of urban infrastructure in middle and low-income countries. 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Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Infectious Diseases",id:"6"},selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/35252",hash:"",query:{},params:{id:"35252"},fullPath:"/profiles/35252",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()