Hypermethylated genes related to MPM.
\r\n\tWe hope to present dozens of algorithms and implementation examples, all in pseudo-code and suitable for use in real-world, large-scale Information Systems and their applications. We also hope to address advanced topics such as mining object-relational databases, spatial databases, multimedia databases, time-series databases, text databases, the World Wide Web, and applications in several fields. The goal is to provide a comprehensive, practical look at the concepts and techniques needed to get the most out of data.
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They convey a wide range of knowledge as a center of academia; teach and research specialized arts and sciences; and develop intellectual, moral, and applied skills (the School Education Act) [1].
Modern universities had their origins in medieval Europe. The oldest university in Europe is said to be the University of Bologna [2] in Italy, which began when a guild of law students organized a “
On the other hand, in Japan, the University of Tokyo was founded in 1877 as the merger and reorganization of Tokyo Kaisei Gakko and Tokyo Medical School [4]. There was no autonomy as in medieval European universities, and it was a powerful state-led bureaucracy training institution. However, in Japan, a bureaucratic training organization called “Daigaku-ryo” had already been established more than a thousand years earlier (670) during the reign of Emperor Tenchi—it was created by the government to learn about the systems and cultures of China and to create an organization as a nation, and it differs greatly from the university organizations in Europe created by the teachers and students themselves [3].
The number of universities doubled from 389 schools (75 national schools, 33 public schools, and 281 private schools) 50 years ago (1971) to 795 schools (86 national schools, 94 public schools, and 615 private schools) as of 2020 (Figure 1), and the number of students also increased, from 1,469,000 to 2,916,000 in 2020. This was greatly influenced by an increase in the population of 18-year-olds. The population peaked in 1966, when the postwar “baby boomer” generation reached the age of 18, at 2.49 million. By 1992, when the generation of their children reached the age of 18, the total stayed fairly steady at 2.05 million. In addition to promoting decentralization, the government announced the deregulation of university establishment standards [5]—that is, the government’s policy of restraining the increase in the capacity of universities and faculties was abolished. As a result, private universities increased from 378 private schools in 1991 to 615 private schools in 2020. The percentage of students advancing to universities has improved dramatically, and the percentage of students advancing to a four-year university reached a record high of 54.4% in 2020, compared with 25.5% in 1991 (Figure 1).
Number of universities and higher education rate in Japan.
Meanwhile, the population of Japan began to decline after peaking in 2008 (128 million people). Due to the declining birthrate, the population of 18-year-olds has continued to decline; it is currently at 1,167,000 (Figure 2). Because of this, and because of the increase in the number of universities due to deregulation, one-third of private universities are under-enrolled [6]. The decline in the quality of university education due to insufficient academic ability and the shortage of students make it difficult for universities to operate. To meet the demands of local communities and society, as well as the diverse needs of students, there should not only be a limited number of universities but many universities should provide education that draws on students’ individuality and attributes, so that a wide variety of educational approaches could be provided in Japan as a whole [7]. For universities to remain seats of learning, teachers and staff should work together to consider their roles, while the administration stabilizes the business foundation.
18-year-old population in Japan.
Modern universities began with the idea envisioned by Wilhelm von Humboldt (1767–1835), the founder of the University of Berlin. He defined universities as institutions that integrate education and research, and emphasized not only lectures but also seminars and practicums, and laboratories of different sorts. That is, he thought that scholarship was something always being produced anew, created by both the professor and the student [3]. This educational philosophy is based in the humanities, and it rejects the idea that vocational education takes precedence over general cultural education. Karl Theodor Jaspers (1883–1969) also described the mission of universities as “the search for truth in a community of researchers and students” [8]. Here as well, research is a basic requirement for universities, and although it is impossible to separate research and teaching, research is regarded as the most important element. In contrast, José Ortega y Gasset (1883–1955) developed a theory of university reform in his book
Kinjo-Yugakkan, which became the basis for Kinjo University, was established in 1904. At that time, there was no school in Ishikawa Prefecture where girls who graduated from higher elementary school could advance to higher education, and to improve girls’ education, Kokichi Kato, a teacher at the prefectural normal school, founded the school with his own money [11]. The educational philosophy of the school was “leading by example,” and “frugality and diligence.” “Leading by example” means doing things before others do, to become a model for such actions, while “frugality and diligence” refer to working and studying hard without extravagances. When it started as a private school, Kinjo-Yugakkan had 29 students, including eight boys. In 1908, a school building was established in Honda-machi, and in 1924, the school was approved as a five-year high school for girls. Furthermore, Kinjo Junior College was founded in 1976. In 1996, the Kinjo Women’s Senior High School was renamed Yugakkan High School and became co-ed.
Kinjo University opened in 2000, and the Faculty of Social Work’s Department of Social Work was established. In 2007, the Department of Physical Therapy was established in the Faculty of Health Services, and in 2013, the Department of Occupational Therapy was added. In addition, in 2015, the Department of Nursing was established in the Faculty of Nursing, and the Graduate School of Rehabilitation was created; with these, Kinjo has become a university specializing in medical and welfare. There are five departments in three faculties, and there are about 1200 students aiming to become medical welfare and childcare/early childcare education professionals. Physical therapists, occupational therapists, nurses, social workers, and care workers are not licensed unless they have taken and passed the national examination. For this reason, medical and welfare universities must provide vocational and professional education also in addition to a liberal arts education and community contributions, which are considered to be the essence of universities.
In reality, since the establishment of our university, many faculty members and students have made social contributions by becoming involved with the community with undergraduate and seminar units. These activities have been useful for regional revitalization and student education, but have rarely led to teachers’ research activities. Therefore, these activities were made into a university-wide initiative, promoting teachers’ research activity. In this era, universities also require “brand power.” The Kinjo Dream Project (KDP) is aimed at developing a system for the promotion of both research and branding by restructuring some established regional collaboration projects while contributing to the community in a more developed manner.
This book therefore focuses on social contribution—one of the proposed roles for universities—and describes the connection between local communities and the social contribution activities that have been carried out over the past 20 years until the establishment of KDP.
The authors have no conflict of interests.
Human malignant pleural mesothelioma (MPM) is an invariably fatal tumor due to its heterogeneity, growing from the serous surfaces of the pleura. Many factors are involved in its occurrence, such as exposure to asbestos fibers and simian virus 40; these factors being those that are strongly associated with the tumorigenesis of this disease. The annual incidence of MPM is relatively low, estimated in a range of 0.6–30/10,00,000, but the global occurrence is expected to increase continuously in future years [1]. MPM is extremely heterogeneous in its morphology and molecular phenotypes. The latency period for MPM development is 10–50 years after asbestos exposure. The prognosis for MPM is generally poor, with a median survival time of 12 months from diagnosis [1].
Intratumor heterogeneity refers to a mixture of phenotypic, functional, and genetic differences within cancer cells with various differentiation or hierarchical statuses within the tumor. It is a common feature in most tumors. This heterogeneity has been considered the greatest obstacle to the effectiveness of most cancer therapies, manifesting itself in its sensitivity to different therapies. Several studies have been focused on genetic alterations as part of the mechanism of tumoral cells for the generation and maintenance of this heterogeneity. In addition, some other studies show the role of epigenetic modifications involved in its heterogeneity. Despite this, there is scarce information about epigenetic modifications that could explain this process [1, 2].
Epigenetic modifications are heritable and stable alterations of genes that do not change the DNA sequence, including DNA methylation, histone modification, and non-coding RNA interference modifications. DNA methylation has been extensively studied in the development of cancer. On the one hand, hypermethylation in cancer-related promoter genes induces the silencing or downregulation of tumor suppressor genes and repair genes. On the other hand, hypomethylation of DNA leads to activation of oncogenes and genomic instability. Several authors suggest that aberration in DNA methylation may play an important role on tumor cells heterogeneity [3, 4, 5].
The exact mechanisms by which asbestos fibers promote the development of cancer are unknown, however, the most accepted theory is the induction of chronic inflammation and signaling pathways in the transformation of reactive oxygen species generated by asbestos fibers. Therefore, this chapter will address an overview of the epigenetic profile of MPM and the mechanisms that promote epigenetic modifications where asbestos fibers might play an important role.
As previously mentioned, asbestos exposure is a primary cause of the development of pleural mesothelioma. Molecular analyses show that asbestos-related carcinogenesis is caused by chronic inflammation that both promote the release of oxygen free radicals that alter intracellular components, and DNA mutation and its consequent transformation. Asbestos fibers also contain iron ions and can induce hemolysis by sequestering iron from hemoglobin. This is particularly important since free iron disproportionately releases H2O2, which consequently releases hydroxyl radicals (OH) that oxidize DNA, and release nucleic acids, proteins, and lipids. This process is exacerbated by the release of cytokines including tumor necrosis factor-alpha from macrophages and high mobility of box group 1 (HMGB1) proteins from necrotic cells, leading to an amplification of the inflammatory response and an increase in cells that are driven to oxidative damage. Damaged oxidized DNA, if not properly repaired, is highly mutagenic and can lead to genomic instability. A multitude of oxidative DNA lesions includes oxidation of DNA bases, baseless sites, single-strand breaking, double-strand breaking, and interchain breaking, all of which require different pathways for proper repair. These last two chain-breaking types are particularly toxic, since they cause replication collapse, as well as allow chromosome rearrangements, chromosome gains, losses, or fragmentation [2].
There are other mechanisms involved in how asbestos fibers cause MPM (Figure 1). Four proposed models related to asbestos fibers induce genetic and cellular damage to cells, in addition to the previously mentioned chronic inflammation. The different molecular models involved in asbestos exposure are explained below:
Reactive oxygen species generated by asbestos fibers with their surface exposed leads to DNA damage and cell membrane rupture. Macrophages that engulf asbestos fibers but cannot digest them also produce abundant reactive oxygen species.
Asbestos fibers are also engulfed by mesothelial cells. Asbestos fibers collected in cells can physically interfere with the mitotic process of the cell. The cycle is cut by the interruption of the mitotic spindles. Another important aspect is the entanglement of asbestos fibers with the chromosomes or mitotic spindles that can give rise to structurally damaged chromosomes such as aneuploidies of normal mesothelial cells.
Asbestos fibers can absorb a variety of proteins and chemicals on the wide surface of asbestos, which can result in the accumulation of dangerous molecules including carcinogens. The asbestos fibers also bind to important cellular proteins and a deficiency of these proteins can also be detrimental to normal mesothelial cells.
Finally, mesothelial cells and macrophages exposed to asbestos release a variety of cytokines and growth factors that induce inflammation and tumor promotion. These include tumor necrosis factor α, interleukin 1β, transforming growth factor β, and platelet-derived growth factor. Tumor necrosis factor-α has been shown to activate nuclear factor-κB, leading to mesothelial cell survival and inhibiting asbestos-induced cytotoxicity. The high mobility group protein box 1 (GAMB1) is released from mesothelial cells, which are exposed to asbestos and then undergo necrotic cell death, promoting an inflammatory response. Thus, aberrantly activated signaling between mesothelial cells, inflammatory cells, fibroblasts, and other stromal cells can create a set of mesothelial cells, which harbor aneuploidy and DNA damage, potentially developing cancer cells and together all these phenomena form a tumoral microenvironment that supports and nurtures them [6, 7, 8].
Possible oncogenic mechanisms induced by asbestos. Abbreviations: HMGB1 = high-mobility group box 1. ROS = reactive oxygen species. TGF-B = transforming growth factor beta. VEGF = vascular endothelial growth factor.
Methylated DNA studied through immunoprecipitation grounded on next-generation sequencing makes it possible to analyze the DNA methylome, which constitutes a useful and efficient tool in the approach of cancer epigenomics [5, 9, 10].
An important and widely described phenomenon in the development of MPM is the epigenetic dysregulation that promotes changes in gene expression [11]. DNA methylation modifications play an important role in the malignant transformation of mesothelioma. Survival in MPM has been attributed to promoter methylation and silencing of genes such as SFRP4, SFRP5, FHIT, and SLCA20.
The methylated CpG islands have been shown to affect different process, such as uncontrolled cell proliferation & differentiation and dysregulations in apoptosis, in the oncogenic process of MPM. It is important to mention that asbestos fibers have been related with increased prevalence of aberrant promoter methylation by controlling the APC and RASSF1 genes, directly affecting the cell cycle [1, 2, 3, 4].
Epigenetic modifications require active maintenance and are potentially reversible, characteristics that make them targets for therapeutic strategies. Multiple DNA methyltransferases and histone deacetylases (HDACs) participate on the regulation of some tumor suppressor genes by gene silencing and chromatin compaction. Therefore, changes in these two enzymes promote disturbances in gene expression and allow deflections in cell proliferation, differentiation, and apoptosis. When HDACs are inhibited, there is a massive production of superoxide radicals and the caspase system is activated, leading to cell death. Additionally, hyperacetylation of non-histone proteins takes place, promoting angiogenesis and tumor cells motility and invasion [12].
DNA modifications are not the only mechanisms involved in tumorogenesis. Epigenetic changes also play an important role in oncogenesis through changes in DNA-associated proteins, modifying their expression. In this regard, the most important changes are DNA methylation and histone deacetylation. These changes lead to important modifications in DNA activity and expression. As a result of this process, some proteins involved in tumorogenesis can be induced and modulated, for example, epidermal growth receptor factor, tumor necrosis factor-alpha protein fusion peptide, transforming growth factor-beta and others. As mentioned above, these changes are induced by epigenetic mechanisms that are potentially reversible [12, 13].
In recent years, inhibiting tyrosinase-like receptors (RTKs) has been used as a therapeutic target because MPM cells have been shown to express high levels of receptors that can bind to key molecules, such as epidermal growth receptor factor (EGFR) and platelet-derived growth factor (PDGF), fibroblast growth receptor factor (FGFR-1y3), transforming growth factor-beta (TGF-B), insulin-like growth factor (IGF-1R), and tumor necrosis factor-alpha protein fusion peptide (NGR-hTNF-alpha). All these molecules undergo through epigenetic changes and play a dead serious role in tumor invasion and angiogenesis [12, 13].
Numerous genes have been shown to be epigenetically downregulated, as the DNA methylation of transcriptional promoters. These changes deregulate several signaling pathways, including the WNT pathway, in which several negative regulators are hypermethylated and silenced [14, 15]. The global epigenetic profile determined by high-throughput analysis differs between MPM and normal pleura, showing that MPM has aberrant methylation in the CpG islands, as has been mentioned [16, 17]. These data support the hypothesis that a specific DNA methylation pathway is induced during mesothelial carcinogenesis.
Kim et al. [1] carried out a study in a patient with MPM, 122 differently regulated genes were found, 118 genes were down-regulated and four were up-regulated by hypomethylation. Therefore, MPM cells may be epigenetically regulated, and DNA methylation plays a main role in intratumorally heterogeneity, characteristic that boost MPM more aggressiveness.
There are sundry important factors that have been related with DNA methylation of gene loci in MPM such as age-related changes, ethnicity, histological subtype, and asbestos exposure. These factors could explain discrepancies between DNA methylation frequencies in published studies, as well as the experimental method used to detect it. In patients diagnosed with MPM, an increased DNA methylation associated with increased age has been reported. Some studies have shown that methylation status of the IGFBP2 (insulin growth factor binding protein) locus and GDF10 (bone morphogenetic protein) locus is significantly higher in MPM in Japanese patients compared with US patients [18, 19].
There are some concrete characteristics that are related to specific genes, for example; RASSF1 suppressor gene has been reported to have a significantly higher frequency of aberrant methylation in epithelioid MPM than in the sarcomatoid subtype [20, 21]. Methylation of MT2A gene, is shown to differ between these two histological subtypes. Epithelioid and sarcomatoid mesotheliomas also have different methylation changes at 87 CpG islands [22, 23]. MT1A and MT2A gene loci associated with DNA methylation have also been described in MPM.
CpG island methylation in the CCND2, CDKN2A, CDKN2B, HPPBP1, and RASSF1 genes has been studied in correlation with asbestos exposure. The RASSF1 DNA methylation locus is related with a higher number of asbestos bodies in the lung. There are different methylation profiles in MPM according with its exposure to asbestos and a positive association between asbestos fiber load and CDKN2A, CDKN2B, RASSF1 methylation status, and MT1A at another 100 loci.
Some differences have been described in DNA methylation for sundry genes between MPM, lung adenocarcinoma, and in non-malignant lung tissues. That’s why, at these days, DNA methylation is an important tool in the diagnosis of MPM [20, 24]. Thus, the DNA methylation profile has potential helpfulness in the diagnostic of MPM and reject of other differential diagnoses. It has been demonstrated by high-throughput analyses for methylation, spanning several thousand CpG islands. It was recently suggested that DNA methylation at three specific loci: TMEM30B, KAZALD1, and MAPK13, could be useful in the differential diagnosis of MPM. In the near future, MPM diagnosis may be based on the methylation profile, but by now, further studies in larger populations are necessary before using a limited number of hypermethylated loci [19, 20, 21].
Other studies have shown alterations in the methylation status of individual genes, such as those HIC1, PYCARD, LZTS1, and SLC6A20. All of these genes have been associated with a good or bad prognosis [22, 23]. Besides, patients with MPM and a low frequency of DNA methylation had longer survival [22, 23, 24].
In view of the aberrant epigenetic events observed in MPM and the clinical value of histone deacetylase inhibitors (HDACis), the latter is currently being studied as a potential diagnostic method. However, insufficient data is yet available on the regulation of histone modifications, despite their crucial role in maintaining chromatin stability. These data are needed to support clinical trials based on HDACis [6, 7, 25, 26].
Each nucleosome is made up of 147 base pairs (bp) of DNA wrapped twice around a histone octamer. Epigenetic regulation of gene expression occurs in the context of chromatin, the basic unit of the nucleosome. Lysine-rich histone tails extend from the nucleosome and provide sites for covalent and reversible binding, promoting processes such as acetylation, methylation, ubiquitination, phosphorylation and SUMOylation, which produce the activation or inhibition of gene expression [8, 27].
DNA methylations represent the most important mechanism regulating major changes in gene expression during normal cell cycle and tissue differentiation, as well as long-term repression of imprinted alleles, germ cell-restricted genes, repetitive DNA, and sequences. Endogenous retrovirals [27, 28, 29]. Normal somatic cells have three major DNA methyltransferases: DNMT1, DNMT3A, and DNMT3B. All these enzymes mediate the transfer of a methyl group from S-adenosyl-methionine to the 5′ position of cytosine in the context of CpG. CpG dinucleotide groups are found in the promoters of approximately 60% of genes. Furthermore, most of these islands are unmethylated, allowing for a relaxed structure (euchromatin) and active transcription [30]. Some other CpG dinucleotides and CpG islands, which are often hypermethylated in normal cells, are scattered throughout the genome [31]. Although there is considerable overlap, DNMT1 preferentially binds hypermethylated DNA and works primarily as a housekeeping methyltransferase, restoring DNA methylation patterns during the process of DNA repair or replication. On the other hand, DNMT3A and 3B mediate de novo DNA methylation after recognition of unmethylated or hypermethylated DNA [30, 31].
It is important to recapitulate that methylation-sensitive transcription factor binding is inhibited by DNA methylation, and these changes promote the recruitment of the CpG methyl-binding domain (MBD) and relevant proteins such as UHRF1, syn3a-containing repressor complexes, NCoRs and histone deacetylases (HDACs), resulting in silent transcriptional heterochromatin output [32, 33, 34].
During the process of malignant transformation, the aberrant orientation and overexpression of some factors involved in DNA methylation promote the epigenetic silencing of genes related to differentiation, many of which are tumor suppressors. On the other hand, tumor suppressor genes can be inactivated by DNA methylation through transitional mutations resulting from deamination of 5-methylcytosine (5-MC) or adduct formation with environmental carcinogens such as benzopyrene [35].
DNA demethylation occurs passively during DNA replication [36, 37]. In addition, DNA can be actively demethylated by oxidation of 5-MC to 5-hydroxymethylcytosine, a ten-eleven translocation (TET) enzyme-mediated reaction [20].
The total amount of methylated CpGs, during malignant transformation, is up to 50%, excluding CpG promoter islands. The genome-wide DNA demethylation is importantly related to a deficient DNA repair process [38, 39, 40, 41]. Besides, it can promote unrepression of imprinted alleles, endogenous retroviruses, and transposable elements, inducing genomic instability [42, 43]. On the other hand, the mechanisms that mediate this phenomenon, such as decreased expression of methyltransferase 1 [44, 45, 46] glycosylase-mediated cleavage of 5-MC and aberrant expression/orientation of TET proteins, have not been fully elucidated [38].
The most widely characterized histone modifications in normal cells and malignant cells have been the acetylation-deacetylation and the methylation-demethylation [1, 2, 43, 47]. Histone acetylation is mediated by a variety of histone acetyltransferases (HAT), increasing the net negative charge leading to DNA repulsion, chromatin relaxation, and gene expression. Some non-histone proteins, including Hsp90, SP1, p53, and HDAC1, are targets for HAT and HDAC. In the other hand, histone deacetylation is regulated by HDAC [48].
Histone lysine methylation is mediated by a variety of histone methyltransferases (KMTs), lysine mediating monomethylation/dimethylation/trimethylation of specific residues, whereas histone demethylation is mediated by histone demethylases [47, 49, 50]. Histone modifications are highly dynamic in response to environmental signals [51, 52]. Unlike histone acetylation, histone lysine methylation does not modify the charge of core histones. Furthermore, histone lysine methylation can promote or inhibit gene expression.
ATP-dependent chromatin remodeling complexes have emerged, in recent years, as critical mediators of the epigenetic regulation of gene expression in normal and malignant cells [53, 54]. To date, four gene families have been described including switch/non-fermentable sucrose (SWI/SNF), SWI mimetic (ISWI), DNA-binding helicase chromodomain (CHD), and INO80, named for their ability to regulate inositol-responsive gene expression. All these complexes have multiple subunits with diverse isoforms and exhibit pleiotropic functions including regulation of gene expression, maintenance of chromatin structure, replication of pericentromeric heterochromatin, repression of ribosomal RNA, and repair of cell damage. DNA [55]. There are several mechanisms by which different families remodel chromatin. For example, the SWI/SNF complexes expose DNA by disassembling the nucleosome, while members of the ISWI, INO80, and CDH families reposition (slide) the nucleosomes and extend the intervening DNA, promoting access to transcriptional factors. These complexes also have an important role in maintaining chromatin structure and genome stability, through mechanisms that reassemble the nucleosome [53, 55].
Studies in transcriptome analysis have revealed that almost 90% of the genome is transcribed as non-coding RNAs (IncRNAs), which are critical mediators of chromatin structure and gene expression in normal cells and malignant transformation [56, 57, 58]. Besides, lncRNAs participate in the recruitment of DNMTs and histone methyltransferases to chromatin [59], adding another layer of epigenetic regulation in normal cells which is altered in malignant tumors.
There are several studies that have shown a relationship between silencing suppressor gene by methylation process and the development of MPL. For example, Christensen et al. [23] examined the DNA methylation status of the promoter of six genes that regulate cell cycle progression at 70 MPM. The extent of methylation of these genes was correlated with lung asbestos burden and overall survival. Goto et al. [60] studied methylation process in more than 6000 GpC islands, comparing twenty MPM versus twenty lung adenocarcinomas, using microarray PCR technique. Their results are interesting because they found out that 387 genes (6.3%) were hypermethylated in mesotheliomas, while the number of hypermethylated gene in lung adenocarcinoma were higher with a total amount of 544 genes (8.8%).
MPL patients’ survival is related with DNA methylation levels. In this way, higher levels of DNA methylation correlate with lower patient survival. Three genes; TMEM30B, KAZALD1 and MAPK13, are specifically hypermethylated in MPM. Several reports have documented tumor suppressor gene silencing related to DNA methylation process in MPM (Table 1) and there is evidence of hypermethylation of some of these genes affecting overall survival.
APC1A | P151NK4B |
APC1B | P16 |
BMP3b | RARB |
CDH1 | RASSF1A |
DAPK | SFRPs |
ESR1 | SLC6A20 |
FHIT | SYK |
IGFBP3 | TMEM30B |
KAZALD1 | THBD |
MAPK13 | TMEM30B |
MGMT | TYMP |
P14ARF | WIF-1 |
Hypermethylated genes related to MPM.
MPM: malignant pleural mesothelioma.
Currently, scientific evidence has shown that recurrent hypermethylation is highly related to tumor suppressor genes in MPM, however, the mechanisms behind this process have been poorly studied. Novel studies have identified TC2N gene as a tumorigenesis promoter by silencing p53. Cytokine signaling participate in modulation process of DNMT expression and mediate hypermethylation of target genes enrolled in some types of cancer such as colorectal carcinoma and erythroleukemia cells [61, 62]. Exposure to asbestos fibers leads to a cytokine cascade induced by high mobility group 1 (HMGB1) or the NLRP3 inflammasome. These cytokines use to change the regulation of the expression of DNMT and other components of the methylation machinery during the process of MPM evolution.
A study of a panel of genes encoding epigenetic regulators in a panel of cultured cell lines derived from asbestos-associated MPM relative to LP-9 (a commercially available normal mesothelial cell line) was recently carried out. Consistent with the study results, TCGA data demonstrate a spectrum of DNMT expression in MPM and suggest that overexpression of DNMT1, DNMT3A, and DNMT3B correlates with decreased survival of pleural mesothelioma patients (Figure 2).
Association between intratumoral DNMT expression levels and surveillance in patients with MPM. The Kaplan Meier waves show that DNMT1, DNMT3A, and DNMT3B expression, measured by RNA-seq technique, has negative impact in patients’ surveillance.
Kim et al. [1] studied gene expression and methylation profiles in pluripotent populations (SP) and non-SP fractions in human MPM samples, using RNA-seq and methylated DNA immunoprecipitation techniques. They found 6400 hypermethylated genes and 3400 hypomethylated genes in SP. Seven hundred and ninety-five genes were upregulated, while three hundred and thirty-five were significantly repressed in SP compared to non-SP fractions. They looked at changes in DNA methylation and expression levels of 122 genes; 118 genes were hypermethylated and downregulated, while 4 were hypomethylated and upregulated. Ten other genes showed hypermethylation and low expression of CpG promoter islands.
The loss of the imprinting process is largely due to DNA hypomethylation. Repression of endogenous retroviral sequences and activation of GC genes can promote malignant transformation by increasing proliferation, genomic instability, and resistance to apoptosis [63, 64].
A fascinating phenomenon can occur during the malignant transformation of somatic cells. The development of highly limited tumor antigens that induce serological and cell-mediated immune responses in cancer patients can be caused by abnormal activation of GC genes [also known as testicular cancer (TC) genes]. As a result, testicular cancer antigens (ATCs) have become popular targets for cancer immunotherapy in recent years [65]. More than 270 GC genes have been registered in the international TC database thus far. Seventy-five percent of these genes are only expressed in normal testes and malignant neoplasms, while the rest have high levels of expression in testes and varying levels of expression in other normal tissues and malignancies. On the X chromosome, around half of the GC genes are encoded. Families of cancer-testis-X (CT-X) chromosomal genes with inverted DNA repeats are common. On the other hand, inverted repetitive DNA sequences or extended families or are not linked to non-X CT genes [66, 67]. Furthermore, CT-X genes are frequently active in malignancies, and genes from families are increased in a tumor-specific manner, implying that the CT-X genes have a transcriptional coregulation and functional link.
In human malignancies, the stage at which the disease is discovered at a specific time corresponds to the degree of CG gene repression. Malignant and aggressive phenotype of cancer cells is promoted activations of this genes. BORIS/CTCFL, for example, upregulates h-TERT and suppresses apoptosis in cancer cells via processes that are still unknown [68, 69]. MAGE-A11 regulates the activity of the tumor suppressor gene RBL1/p107 [63]. MAGE-A11 inhibits the tumor suppressor gene RBL1/p107, while MAGE-B2 promotes cell cycle advancement by increasing E2F activity. MAGE-A2 and MAGE-C2 prevent p53 from binding to target promoters, changing its activities and leading to p53 deacetylation (inactivation) or enhanced ubiquitin-mediated degradation. The absence of CG gene regulation does not appear to be just a symptom of pluripotency, as it is accompanied with chromosomal hypomethylation. In human ESC, mesenchymal stem cells, and adipose-derived stem cells, Loriot et al. [70] found no overexpression of 18 different CG genes. In induced pluripotent stem cells (iPSCs) produced from normal small airway epithelial cells, transcriptional repression of CG genes such as NY-ESO-1, MAGE-A1, and MAGE-A3, which are generally located upward in thoracic malignant tumors, has been detected, which is consistent with these findings. Although these findings imply that iPSC reprogramming is partial, induction of CG genes in cancer cells may necessitate more extensive DNA hypomethylation as well as activation of tissue-specific transcription factors.
There is currently such little information on the expression of CG genes in MPM. MAGE1--4, NY-ESO-1, GAGE1-2, GAGE1-6, SSX2, SSX1-6, and RAGE-1 expression in five MPM lines was compared to normal mesothelial cells employing RT-PCR techniques, according to Sigalotti et al. [71]. In these MPM lines, diverse expressions of the CG gene were identified, with each line exhibiting a unique profile, as previously reported for lung malignancies [72]. None of these genes were found in normal mesothelial cells [71, 73].
Polycomb group proteins (PcG) play an important role as regulators of stem cell pluripotency and differentiation [74], as well as inappropriate gene expression during cancer transformation [75, 76]. In mammals, two main Polycomb repressor complexes (PRCs) have been discovered. PRC-2 is an initiating complex that causes trimethylation of histone 3 lysine and contains the subunits EZH1/EZH2, SUZ12, EED, and RBAP46/48 (H3K27Me3).
PCAF, PHC, RING1, CBX, and BMI1 are components of the housekeeping complex PRC-1, which mediates the ubiquitination of H2AK119 (H2AK119Ub). CRC recruitment and heterochromatin growth are aided by these histone marks, which are frequently detected in the context of DNA hypermethylation and gene suppression [75, 76]. Several proteins, such as including JARID2 and members of the sex comb-like family (ASXL), interact with EZH2 and SUZ12 to lead PRC-2 to polykyl response elements (PRE) throughout the genome [77, 78]. Goto et al. [79] investigated gene repression in MPM and observed that a subset of genes repressed in MPM had H3K27Me3 without DNA hypermethylation, implying that disruptions in polycomb gene expression may play a role in MPM etiology [80, 81].
Several immunoblotting investigations studies revealed that MPM cells overexpress EZH2 with associated increases in H3K27Me3 levels when compared to normal mesothelial cells. Another set of tests, which included QRT-PCR, immunoblotting, and IHC, revealed that EZH2 was overexpressed in almost 80% of primary MPMs (most of which were epithelioid histology). As a result of these findings, it was identified that EZH2 is overexpressed in MPM and that PRC-2 could be considered as a potential therapeutic target in these cancers. The overexpression of EZH2 in MPM was verified by TCGA analysis, as was a strong link between EZH2 upregulation and lower MPM patient survival (Figure 2A). Further TCGA analysis reveals that SUZ12 overexpression is associated with poor survival in MPM patients (Figure 2B). On the other hand, there is no evidence about MPM patients’ survival related to EED expression (Figure 2C).
The foregoing findings are especially important in light of recent findings that inactivating mutations in BRCA-associated protein 1 (BAP1), which encodes a nuclear ubiquitin hydrolase with several functions, are found in uncommon familial MPMs as well as almost 60% of sporadic MPMs. H2AK119Ub is ubiquitinated, for example.
LaFave et al. [82] discovered that BAP1 mutations, which are linked to protein expression loss, enhanced the expression of EZH2 and SUZ12 in MPM cells in a series of experiments. Likewise, overexpression of EZH2 was related to lower levels of H4K2Me1 and less occupancy of L3MBTL2 (an unusual polycomb protein that identifies this repressive histone mark) inside the EZH2 promoter in BAP1 mutant cells. Despite the strong connection between BAP1 mutations and repression of Polycomb stem cell targets, no specific clinical manifestation of BAP1 mutant MPM has been identified. Somatic mutations in BAP1 appear to be more common in current or past smokers with MPM [83].
SWI/SNF are mammalian homologs of yeast trithorax complexes. Their major purpose is to antagonize PRC-2’s repressive effects by destroying DNA-nucleosome connections allowing movement and ejection, or by switching nucleosomes to increase factor accessibility transcription to DNA [84, 85]. In human malignancies, the genes encoding the SWI/SNF complexes are commonly altered, with various subunit mutations related to specific cancer histologies.
Yoshikawa et al. [86] used whole exome sequencing to identify a substantial number of mutations in genes involved in the SWI/SNF pathways, including homozygous SMARCA4, ARID2, and PBRM1 mutations in short-term established MPM lines [86, 87]. They also evaluated at the loss of somatic copies in the 3p21 region (which is roughly 10.7 Mb in size and contains 251 genes) in 33 MPM samples, using techniques including comparative genomic matrix high-density hybridization (a-CGH) and next-generation targeted sequencing (NGS). Bi-allelic deletions (3 Kb) were observed in 46 genes, four of which have been associated to malignant tumors, including two SWI/SNF-related genes [PBRM1 (15%) and SMARCC1 (6%)], BAP1 (48%) and SETD2 (27%). More than 200 MPM were studied in a recent thorough genomic investigation.
Bueno et al. [88] described mutations in genes encoding SWI/SNF components in 8% of the samples, as well as mutations in two histone methyltransferases (SETDB1 and SETD5) in about 3% of the samples. The discrepancies between the results reported by Yoshikawa et al. [87] and Bueno et al. [88] may be attributable to the identification of minuscule deletions by high-density, a-CGH, and specific NGS that are not detectable by conventional NGS techniques. To establish final conclusions, more studies are needed to determine the frequency and clinical significance of SWI/SNF mutations in mesothelioma.
MPM inhibits tumor suppressor genes by promoting LOI and repression of CG genes by site-specific hypermethylation of DNA and/or polycomb repressor complexes in the context of hypomethylation of the genome. This “DNA methylation paradox” mimics epigenomic conditions in normal germ cells and lays the groundwork for epigenetic regimens that restore tumor suppressor gene expression and trigger growth arrest/apoptosis. Upregulation of CTAs, development of viral mimicry by derepression of endogenous retroviruses, and control of the tumor microenvironment all help to boost antitumor immunity [89, 90].
DNMTs are potential targets for MPM treatment because of their direct functions in suppressing tumor suppressor genes and maintaining pluripotency [91, 92]. Previous clinical attempts to inhibit DNMT activity in MPM, however, have failed miserably. Yogelzang et al. [93] showed a 17% objective response rate in 41 MPM patients who received 120 h of continuous dihydro-5-azacytidine infusions. Amazingly, 6 years following treatment, the single responder was disease-free. The lack of efficacy of DNA hypomethylating drugs in solid tumors could be due to their usage at maximum tolerated doses, resulting in myelosuppression, rather than prolonged use at lower doses to obtain pharmacodynamic effects without systemic toxicity. The Phase I decitabine trial (DAC) clearly demonstrates that chronic exposures are required to achieve maximum gene induction effects in cancer tissues [94].
Furthermore, 5-AZA and DAC administered IV, SQ , or PO have short half-lives (less than 5 min) and poor biodistribution, limiting their potential utility in patients with solid tumors. Cytidine deaminase (CDA), which is found in practically all organs but mainly the gastrointestinal system, quickly inactivates these molecules [95, 96]. Documented toxicity increases Cmax and t1/2 (>50 nM and 4 h, respectively) as well as biodistribution of oral decitabine, decreasing inter-patient variability in drug levels significantly [95, 96, 97, 98]. Significant increases in fetal hemoglobin, without neutropenia, thrombocytopenia, or lymphopenia, are indicative of hypomethylation of systemic DNA caused by oral DAC-THU. A phase II trial (NCT02664181) is currently underway at the Cleveland Clinic and NCI to examine whether DAC/THU can improve responses to nivolumab when given as second-line therapy to patients with non-small cell lung cancer. Despite encouraging preclinical data [26], efforts to target HDAC on MPM have also been disappointing.
As second- or third-line therapy, Krug et al. [99] randomized 661 MPM patients to receive the HDAC inhibitor vorinostat or placebo. Overall survival, as well as the drug’s safety and tolerability, were the key outcomes. Vorinostat-treated patients had a median OS of 30.7 weeks (95% CI 26.7–36.1) compared to 27 weeks (95% CI 23.1–31.9) for placebo-treated patients. Given the absence of evidence for HDAC upregulation in MPM and the limited antitumor effects of HDAC inhibitors alone in preclinical tests, the lack of efficacy of the single-agent vorinostat in patients with MPM is not surprising. Combinated techniques, such as using HDAC inhibitors to sensitize cells to TRAIL-mediated apoptosis or flavopiridol to boost romidepsin-mediated growth arrest and death, might be helpful for future clinical trials. Hypomethylating drugs, on the other hand, do not appear to lessen the incidence of mesothelioma after asbestos exposure. In fact, non-solid cancers such leukemias, lymphomas, and other myelodysplastic syndromes show the best benefits with this medicine.
It is feasible that BAP1 mutations could be used for MPM therapy in the future. BAP1 promotes the recruitment of the polychial deubiquitinase PR-DUB complex to DNA damage sites by stabilizing BRCA-1 and promoting poly (ADP-Ribose) dependent recruitment of the polychial deubiquitinase PR-DUB complex to DNA damage sites. This activity is dependent on deubiquitinase activity and BAP1 phosphorylation. BAP1 mutations, which invariably show as a loss of function, cause BRCA-1 levels to drop and double-stranded DNA repair to be inhibited [100, 101, 102]. A BAP1 isoform including part of the catalytic domain sensitized MPM cells to the PARP1 inhibitor, according to Parotta et al. [102]. (Olaparib). Concomitant treatment with GDC0980, a dual PI3K-mTOR inhibitor that is downregulated by BRCA-1, could improve this sensitivity. These strategies could improve responses to cisplatin/pemetrexed in patients with BAP1 mutant MPM and should be evaluated in future clinical trials.
There is considerable interest in chromatographic remodeling agents with adoptive cell transfer or immune checkpoint inhibitors for cancer therapy, given the extensive preclinical studies showing DNA demethylating agents, HDAC inhibitors, and KMT inhibitors in the immunomodulatory effects of potentials [103]. In a syngeneic mouse tumor model, cytolytic T lymphocytes target testicular cancer antigen in vivo using decitabine to destroy metastatic cancer. The preclinical basis for combining gene induction regimens with cancer adoptive immunotherapy was established in these studies. Furthermore, novel microenvironmental data are likely to have a substantial impact on the outcomes of clinical trials for epigenetic treatments and immunotherapies [89].
While malignant pleural mesothelioma is a disease with a low incidence worldwide, with aggressive behavior, its survival does not go beyond 12 months once the diagnosis is made [1, 2]. Its origin has been related to the chronic exposure of asbestos as the main factor. Also, asbestos fibers have been an essential component in structural changes at the molecular level, with much evidence about its genetic behavior and to a lesser extent, its epigenetic behavior. All of this gives it a fairly heterogeneous behavior [13, 14, 15]. New molecular techniques allow a broader understanding of the carcinogenesis of this tumor and an approach to new diagnostic tools. Epigenetic dysregulations require active maintenance and are potentially reversible, making them a therapeutic target [7, 23, 30].
The study of methylome has made it possible to carry out differential diagnoses thanks to the methylation of some specific loci, such as TMEM30B, KAZAZD1, MAPK13 and to demonstrate greater survival rates in patients with low frequencies of methylations [16, 17, 28].
It is important to mention the exposure to asbestos fibers as the main resistance factor associated with the methylation of tumor suppressor genes seen in pleural mesothelial cells such as APC and RASSF1. Additionally, there are direct cellular effects such as chronic inflammation measured by free radicals leading to DNA oxidation, hemolysis with the release of hydroxyl ions, intrachain breakdown plus subsequent chromosomal fragmentation, and production of pro-inflammatory cytokines with higher expression of angiogenic growth factors, another aspect that can be considered a potential therapeutic objective. Genomic responses related to methylation conclude in a gene silencing, most likely in tumor suppressor genes such as SFRP4, FHIT, SLCA20 [69, 71, 80]. Another diagnostic approach that can be observed by methylation is the overexpression of DNMT in patients with MPM and consequently could be an attractive therapeutic target, however, clinical efforts for its inhibition have been disappointing and future studies should focus on the therapeutic approach to the inhibition of DNMT.
A greater association of methylation has been seen in advanced ages and ethnic groups such as the Japanese population. However, the greater association related to histological changes in proliferation, differentiation, invasion, and reduction of apoptosis has been seen with the increased methylation of CpG islands in genes such as CCND2, CDKN2A, and associated with asbestos bodies with RASSF1.
Although methylation is the most studied epigenetic mechanism, there are other modifications that lead to the silencing of tumor suppressor genes, such as the activation of the Polycomb complex and the mutation of the SWI/SNF pathway [82, 83]. Deacetylation mediated by HDAC has been seen in the p53 gene and other aspects such as HAT-mediated acetylation or demethylation by KDMs.
The modification in histone features such as stability in chromatin has a great relationship with HDCAs, thus making them a potential therapeutic target. There are few studies with inhibitors such as vorinostat, however, where there are no positive results due to the low expression in MPM.
Finally, it is clear that there is much to know about the modifications and/or epigenetic changes in MPM. The current evidence of the molecular mechanisms opens up another panorama for us to adjust personalized therapeutic strategies aimed at reversing normal changes and thus be able to identify in a timely manner those patients who are susceptible to such treatments. Therefore, clinical trials should focus on those epigenetic markers that at some point in their disease are overexpressed or silenced.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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On grounds of above it is implied, the process of solidification constitutes an important aspects in the production of a defect free casting.",book:{id:"10432",slug:"casting-processes-and-modelling-of-metallic-materials",title:"Casting Processes and Modelling of Metallic Materials",fullTitle:"Casting Processes and Modelling of Metallic Materials"},signatures:"Upendra Kumar Mohanty and Hrushikesh Sarangi",authors:[{id:"328540",title:"Prof.",name:"Hrushikesh",middleName:null,surname:"Sarangi",slug:"hrushikesh-sarangi",fullName:"Hrushikesh Sarangi"},{id:"328543",title:"Prof.",name:"Upendra Kumar",middleName:null,surname:"Mohanty",slug:"upendra-kumar-mohanty",fullName:"Upendra Kumar Mohanty"}]},{id:"48856",title:"Silicon Carbide in Microsystem Technology — Thin Film Versus Bulk Material",slug:"silicon-carbide-in-microsystem-technology-thin-film-versus-bulk-material",totalDownloads:2887,totalCrossrefCites:4,totalDimensionsCites:10,abstract:"This chapter looks at the role of silicon carbide (SiC) in microsystem technology. It starts with an introduction into the wide bandgap (WBG) materials and the properties that make them potential candidates to enable the development of harsh environment microsystems. The future commercial success of WBG microsystems depends mainly on the availability of high-quality materials, well-established microfabrication processes, and economic viability. In such aspects SiC platform, in relation to other WBG materials, provides a clear and competitive advantage. The reasons for this will be detailed. Furthermore, the current status of the SiC thin film and bulk material technologies will also be discussed. Both SiC material forms have played important roles in different microsystem types.",book:{id:"4721",slug:"advanced-silicon-carbide-devices-and-processing",title:"Advanced Silicon Carbide Devices and Processing",fullTitle:"Advanced Silicon Carbide Devices and Processing"},signatures:"Mariana Amorim Fraga, Matteo Bosi and Marco Negri",authors:[{id:"9292",title:"Dr.",name:"matteo",middleName:null,surname:"bosi",slug:"matteo-bosi",fullName:"matteo bosi"},{id:"38456",title:"Dr.",name:"Mariana",middleName:null,surname:"Amorim Fraga",slug:"mariana-amorim-fraga",fullName:"Mariana Amorim Fraga"},{id:"175671",title:"MSc.",name:"Marco",middleName:null,surname:"Negri",slug:"marco-negri",fullName:"Marco Negri"}]},{id:"46237",title:"Corrosion Resistance Through the Application of Anti- Corrosion Coatings",slug:"corrosion-resistance-through-the-application-of-anti-corrosion-coatings",totalDownloads:7398,totalCrossrefCites:11,totalDimensionsCites:32,abstract:null,book:{id:"3817",slug:"developments-in-corrosion-protection",title:"Developments in Corrosion Protection",fullTitle:"Developments in Corrosion Protection"},signatures:"Api Popoola, OE Olorunniwo and OO Ige",authors:[{id:"169258",title:"Dr.",name:"Patricia",middleName:null,surname:"Popoola",slug:"patricia-popoola",fullName:"Patricia Popoola"}]},{id:"46235",title:"Corrosion Detection for Automated Visual Inspection",slug:"corrosion-detection-for-automated-visual-inspection",totalDownloads:3578,totalCrossrefCites:18,totalDimensionsCites:32,abstract:null,book:{id:"3817",slug:"developments-in-corrosion-protection",title:"Developments in Corrosion Protection",fullTitle:"Developments in Corrosion Protection"},signatures:"Francisco Bonnin-Pascual and Alberto Ortiz",authors:[{id:"124589",title:"Prof.",name:"Alberto",middleName:null,surname:"Ortiz",slug:"alberto-ortiz",fullName:"Alberto Ortiz"},{id:"169256",title:"Ph.D. Student",name:"Francisco",middleName:null,surname:"Bonnin-Pascual",slug:"francisco-bonnin-pascual",fullName:"Francisco Bonnin-Pascual"}]}],onlineFirstChaptersFilter:{topicId:"944",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82118",title:"Surface Hardening of Stainless Steel",slug:"surface-hardening-of-stainless-steel",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.105036",abstract:"The addition of nitrogen to stainless steel improves mechanical and corrosion properties. Nitrogen-bearing stainless steel (HNSS) is a new corrosion-resistant alloy class exhibiting better tribological properties. High-pressure and powder metallurgy techniques were developed for the fabrication of HNSS. Solid-state routes allow nitrogen introduction through thermochemical, implantation, or plasma surface treatments. High-temperature gas nitriding (HTGN), carried out in an N2 atmosphere in the 1000°C range, allows N uptake, obtaining thick, ~0.5–1.0 wt.% N austenitic cases. HTGN is different from conventional nitriding, performed in the 500°C range, where intense CrxNy precipitation occurs, impairing the corrosion resistance. Low-temperature plasma nitriding (LTPN) introduces more N in solution, and colossal supersaturated expanded phases (~45 at.%N) are formed. N supersaturation and compressive stresses increase the hardness of the surface layer to 10–14 GPa. Ferritic, martensitic, duplex, and precipitation-hardened stainless steels can be surface-treated by LTPN, obtaining expanded ferrite and martensite. However, single LTPN stainless steel may prematurely fail when submitted to high loading, as the thin and hard expanded layers collapse due to lack of load-bearing capacity. Duplex-nitriding treatment (HTGN + LTPN) results in a thick nitrogen-rich hardened austenite substrate layer, granting mechanical support and adhesion to the expanded austenite layer.",book:{id:"11076",title:"Stainless Steels",coverURL:"https://cdn.intechopen.com/books/images_new/11076.jpg"},signatures:"André Paulo Tschiptschin and Carlos Eduardo Pinedo"},{id:"81579",title:"Welding Based Additive Manufacturing: Fundamentals",slug:"welding-based-additive-manufacturing-fundamentals",totalDownloads:32,totalDimensionsCites:0,doi:"10.5772/intechopen.104768",abstract:"Additive Manufacturing (AM) has drawn abundant attention over the past decades in the manufacturing and fabrication industries, especially to make part models and prototypes. This chapter introduces a potential welding based AM process called Wire Arc Additive Manufacturing (WAAM) for the fabrication of near-net shaped metal components including stainless steel components. To start with traditional AM processes, various fundamental traditional AM for the fabrication of components have been presented. Wire Arc Additive Manufacturing (WAAM) has been explained with its variants, synonyms, different welding processes to suit WAAM particularly to weld stainless steel metal; primary process selections for working with WAAM, important metals, and alloys that could be used in WAAM have been elaborated. A case study for WAAM fabrication of AISI 316 L stainless steel plate is included to introduce the fabrication of metal components using WAAM. Further, the most common defects which possibly play a vital role in WAAM components fabrication and a few of the future challenges regarding WAAM development are discussed. Fundamental information covered in this chapter could be more beneficial to beginners for the understanding of WAAM process generally including stainless steel component fabrication in a lucid tactic.",book:{id:"11076",title:"Stainless Steels",coverURL:"https://cdn.intechopen.com/books/images_new/11076.jpg"},signatures:"Maruthasalam Sowrirajan, Selvaraj Vijayan and Munusamy Arulraj"},{id:"80664",title:"Dependence of Corrosion Resistance of Austenitic Chromium-Nickel Steels on the Magnetic State of Austenite",slug:"dependence-of-corrosion-resistance-of-austenitic-chromium-nickel-steels-on-the-magnetic-state-of-aus",totalDownloads:59,totalDimensionsCites:0,doi:"10.5772/intechopen.102388",abstract:"Corrosive behavior of austenitic chromium-nickel steels from the magnetic state (parameter χ0) of austenite, pre-formed to interact with aggressive media are research. Correlation between the rate K of pitting corrosion and the specific magnetic susceptibility χ0 of austenite was experimentally established. It is experimentally established that the corrosion resistance of austenitic steels AISI304, 08Cr18Ni10, AISI 321, 08Cr18Ni10Тi (containing a low amount of δ-ferrite ∼0.005…0.5%) depends on the magnetic state of austenite: the corrosion rate of steel decreases with increases χ0 austenite. The tendency of change in the corrosion rate of austenitic alloy with a high nickel content 06Crh28NiMoCuTi (not contain δ-ferrite) has the opposite character: with increasing χ0, the corrosion rate of the alloy increases is revealed. For austenitic chromium-nickel steels, the corrosion rates of the individual (austenite (A), δ-ferrite (F), strain-induced α′-martensite (M)) and total (A + F, A + M and A + F + M) phases are determined. It is proposed to predict corrosion according to the specific magnetic susceptibility χ0 of austenite and the amount δ-ferrite.",book:{id:"11076",title:"Stainless Steels",coverURL:"https://cdn.intechopen.com/books/images_new/11076.jpg"},signatures:"Gennadii Snizhnoi"},{id:"80199",title:"The Evaluation of the Comparative Corrosion Behaviour of Conventional and Low-Nickel Austenitic Stainless Steel: Hercules™ Alloy",slug:"the-evaluation-of-the-comparative-corrosion-behaviour-of-conventional-and-low-nickel-austenitic-stai",totalDownloads:55,totalDimensionsCites:0,doi:"10.5772/intechopen.102381",abstract:"Austenitic stainless steels require approximately 8% Ni to maintain austenitic microstructure at room temperature for alloys such as 304 stainless steel (304SS). Ni contributes approximately 60% of the total material cost and its price fluctuates, making the cost of austenitic stainless steel unpredictable. The use of low-nickel austenitic stainless steels as a substitute has been considered in order to remedy costs associated with Ni price fluctuations. Alloying elements such as Mn and N have been considered, however they have been found to reduce corrosion resistance. A new alloy namely Hercules™ has been developed with reduced Ni content (1.8–2% Ni). This chapter presents a comparative study of the corrosion behavior of Hercules™ and 304SS in different solutions. The alloys were evaluated using cyclic polarisation technique and immersion tests. The results demonstrated that the corrosion resistance of Hercules™ is comparable to that of 304SS. This presents the alloys as potential industrial substitutes of each other.",book:{id:"11076",title:"Stainless Steels",coverURL:"https://cdn.intechopen.com/books/images_new/11076.jpg"},signatures:"Duduzile Nkomo and Nomsombuluko Masia"},{id:"80346",title:"Nitrogen Supersaturation of AISI316 Base Stainless Steels at 673 K and 623 K for Hardening and Microstructure Control",slug:"nitrogen-supersaturation-of-aisi316-base-stainless-steels-at-673-k-and-623-k-for-hardening-and-micro",totalDownloads:59,totalDimensionsCites:1,doi:"10.5772/intechopen.102387",abstract:"The high-density plasma nitriding at 673 K and 623 K was employed to make 10% of nitrogen supersaturation on AISI316 base austenitic stainless steels. The processing parameters and nitrogen-hydrogen gas flow ratio were optimized to increase the yield of N2+ ion and NH-radical for efficient nitriding. The nitrided AISI316 specimens were prepared for multidimensional analysis to describe the fundamental features of low-temperature plasma nitriding. First, macroscopic evaluation revealed that nitrogen supersaturation induced the γ-lattice expansion and the higher nitrogen content than 4% of mass in depth. The mesoscopic analysis describes the holding temperature and initial grain-size effects on the microstructure changes. Plastic straining, grain-size refinement, and nitrogen zone-boundary diffusion processes advance with nitrogen supersaturation to drive the inner nitriding behavior. The microscopic analysis explains the microstructure refinement, the two-phase structuring, and the microstructure modification. Through this multi-dimensional analysis, the essential characteristics of the low-temperature plasma nitriding of 316 austenitic stainless steels were precisely understood to extend the engineering treatise on the bulk nitrogen stainless steels for surface modification and treatment of stainless steels by nitriding. This plasma nitriding was applied to strengthen and harden the AISI316 wire surfaces toward its application on surgery wires.",book:{id:"11076",title:"Stainless Steels",coverURL:"https://cdn.intechopen.com/books/images_new/11076.jpg"},signatures:"Tatsuhiko Aizawa, Tomomi Shiratori, Tomoaki Yoshino, Yohei Suzuki and Takafumi Komatsu"},{id:"79904",title:"Corrosion Resistance, Evaluation Methods, and Surface Treatments of Stainless Steels",slug:"corrosion-resistance-evaluation-methods-and-surface-treatments-of-stainless-steels",totalDownloads:106,totalDimensionsCites:1,doi:"10.5772/intechopen.101430",abstract:"Stainless steels are widely recognized and find applications in many engineering industries and companies due to their excellent properties including high resistance to corrosion as a result of their minimum 10.5% chromium content, exceptional strength and durability, temperature resistance, high recyclability, and easy formability. In the present book chapter, the basic concepts of stainless steel including its applications, classifications, and corrosion properties will first be discussed. Thereafter, their corrosion behaviour will then be explained. The various methods by which the corrosion resistance behaviour can be significantly improved including surface treatments such as coatings/electrodepositions, alloying, mechanical treatment, and others will be discussed in detail.",book:{id:"11076",title:"Stainless Steels",coverURL:"https://cdn.intechopen.com/books/images_new/11076.jpg"},signatures:"Temitope Olumide Olugbade"}],onlineFirstChaptersTotal:8},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"117248",title:"Dr.",name:"Andrew",middleName:null,surname:"Macnab",slug:"andrew-macnab",fullName:"Andrew Macnab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}}]}},subseries:{item:{id:"90",type:"subseries",title:"Human Development",keywords:"Neuroscientific Research, Brain Functions, Human Development, UN’s Human Development Index, Self-Awareness, Self-development",scope:"