\r\n\tThe WHO classification in 2007; was based on the histogenesis and cell origin of the tumor. In the latest classification made in 2016; to better characterize the tumor and obtain better data on its prognosis; The combination of molecular and genetic biomarkers and histopathological features of the tumor was used. Despite all current treatment approaches, the median survival time is around 12 months in most GBM patients. Compared with the situation of some types of successfully treated cancers; the survival time of GBM patients is not at an acceptable level today. In the treatment of CNS tumors; surgery, chemotherapy, and radiation treatments (x-rays, gamma rays, electron and proton beams) are used. The therapeutic potential of chemotherapy; New strategies are needed to increase drug concentration at the diseased site, as this largely depends on the ability of the chemotherapeutic agent to achieve effective concentrations at tumor localization. Based on our better understanding of the genetic and molecular characteristics of CNS tumors; Targeted therapies, including vaccines, and treatment protocols such as immunotherapy are promising developments.
\r\n\r\n\tThis book supposes to be written by many authors who have an internationally honored place in their field to share their ideas about the treatment of CNS tumors. Surgery, Radiotherapy, Chemotherapy and Antiangiogenic Therapy Protocols, Immunotherapy, Molecular Therapy, Specific target-agents therapy with Nanoparticles and Gene Therapy for CNS tumors among the book chapters.
\r\n\tIn these sections; there are many practical pieces of information that can help the students who graduated from the Medicine Faculty and specialist doctors who are interested in Neurosurgery.
SARS-CoV-2 has four main structural proteins: the spike protein (S protein), the nucleocapsid protein (N protein), the matrix protein (M Protein), and envelope protein (E protein) [1, 2]. The SARS-CoV-2 infection starts when the virion enters the host’s cell, through the connection between the viral S protein and the ACE2 receptor and TMPRSS2 on the host’s cells, similarly to severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) [3].
ACE2 and TMPRSS2 are highly expressed in the lungs, partially explaining the high incidence of respiratory disorders. Nevertheless, ACE2 and TMPRSS2 are expressed in many other different organs in the human body, such as the brain, heart, liver, kidney, colonic epithelial cells, intestine luminal cells, and small intestinal enterocytes [4], with reports of SARS-CoV-2 infection on multiple organs [5]. In addition, SARS-CoV-2 may generate a systemic and exacerbated inflammatory response named “cytokine storm”, which can lead to viral sepsis [6].
Several systemic biomarkers have been associated with the progression of the disease, such as creatinine, urea, C-reactive protein, ferritin, lactate dehydrogenase, and D-dimers in the blood, increase in the neutrophil-to-lymphocyte ratio, and reduction in platelet count in the blood [7, 8, 9, 10, 11, 12, 13, 14, 15]. During COVID-19 the increase in blood levels of chemokines and cytokines increases the pro-inflammatory stimulus and recruitment of immune cells to the infection site. Several risk factors contribute to the disease’s severity, such as comorbidities and co-infections [16, 17, 18] In this chapter, the current knowledge about the innate and adaptative immune response during COVID-19 and the influence of comorbidities will the reviewed.
Upon infection by SARS-CoV-2 several chemokines (CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL9, and CXL10) and pro-inflammatory cytokines (IFN-γ, TNF, IL-1, IL-6, IL-12) are released, these molecules will induce cell activation, migration, and infiltration of the infected tissue by innate immune cells like monocytes and neutrophils and further activate local cells such as resident macrophages [19]. These cells will further increase the local production of pro-inflammatory mediators, which could result in tissue damage, such as alveolar damage, formation of edema, and reduced lung capacity. In addition, cytokines can generate a systemic effect, resulting in damage to other organs (kidney, liver, spleen, among others) [20]. An increase in circulating pro-inflammatory monocytes and nonclassical monocytes are commonly observed in COVID-19 patients [21, 22].
Concomitantly, the number of neutrophils in the blood increases, and the infiltration of neutrophils to the infected tissue. Upon infiltration, neutrophils release inflammatory mediators, cytokines, and neutrophil extracellular traps (NETs) which can further increase tissue injury and cellular death [23, 24]. The local production of pro-inflammatory factors, viral particles, and cellular death induces the activation of macrophage and dendritic cells (DCs), which will further increase the production of cytokines and chemokines and antigen presentation [20, 25] DCSs are commonly referred to as professional antigen-presenting cells (APCs) and integrate innate and adaptive immune response. In COVID-19 they can uptake SARS-CoV-2 viral particles, be activated, migrate to lymphatic tissue, initiate antigen presentation, and trigger adaptive immune response. Nevertheless, DCs can also be infected by SARS-CoV-2 [26], reducing quantitatively, generating functional impairment, and lower lymphocyte immune response [27].
The complement system has also been implicated in the pathogenesis of COVID-19. The activation of C3 and C5 complement components are correlated with disease severity and lung biopsy from severe COVID-19 patients presented high C3-fragment content [28]. C3-deficient mice are partially protected from respiratory dysfunction after SARS-CoV-1 infection, exhibiting less inflammatory infiltrate in the lungs, reduced production of cytokines and chemokines, but similar viral load in the lung tissue as Wild Type mice [29]. Importantly, treatment with anti-C5a antibodies resulted in clinical improvement in COVID-19 patients [28]. Indicating a possible use of complement-inhibitor to ameliorate lung injury in COVID-19 patients.
The role of eosinophils and basophils in COVID-19 is yet to be fully comprehended. To the moment, a negative correlation is established between circulating eosinophil and basophil count and COVID-19 severity, with patients exhibiting an increase in those cells upon SARS-CoV-2 clearance [30, 31]. Mast cells (MCs) may also play a role in COVID-19, since they can be activated by viral products and release chemokines, cytokines, and inflammatory mediators, increasing vascular permeability and cellular infiltrate [32]. A few reports have indicated that COVID-19 inflammatory syndrome is in many aspects similar to Mast cell activation disease [32, 33].
The frequency of mononuclear and polymorphonuclear myeloid-derived suppressor cells also increases in the blood, but not in the lungs, of COVID-19 patients according to the severity [15, 34]. Importantly, these cells do maintain their immunosuppressive functions in COVID-19 patients [35].
The hyperinflammatory state is also accompanied by a dysregulated anti-inflammatory state, with an increased early IL-10 production, which could curb the anti-viral immune response [36], and impaired T cells (CD4+ and CD8+) and T regulatory cells function [37].
Patients with moderate and severe COVID-19 commonly present a reduction in circulating lymphocytes (T cells, B cells, natural killer cells). T CD4+ and T CD8+ cells are reduced in moderate COVID-19 patients and further reduced in more severe patients, with or without a significant change in CD4+/CD8+ ratio [38, 39]. A few reports have identified patients with a specific reduction in CD8+ cells, which is associated with poor prognosis [38]. The reduction of B cells and innate lymphocytes, like NK cells, has also been reported, but to the moment are not currently associated with severity or prognosis [40].
The mechanism for the reduction in lymphocytes is still under investigation, several reports indicate that exhaustion and apoptosis may be the primary causes of lymphopenia [41], and one report indicating direct lymphocyte infections by SARS-CoV-2 [42]. Due to the central role of lymphocytes on anti-SARS-CoV-2 immune response, several interventions to modulate the T cell proliferation or apoptosis are also being investigated [43].
Although the reduced T cell count in the blood of COVID-19 patients may reflect the recruitment to infected tissue or be influenced by the use of steroid treatment to curb the inflammation, some studies have also reported significant T cell reduction in secondary lymphoid organs of patients infected with SARS-CoV-2 [44].
Even with the reduction in lymphocytes, T cell receptor analysis indicated that COVID-19 patients do present an increase in SARS-CoV-2-specific T-cells [45]. Proliferation markers, such as Ki67, and activation markers, such as CD28 and HLA-DR, are increased in both CD4+ and CD8+ cells, including activated, effector, and memory T-cells, in COVID-19 patients in comparison to recovered patients and non-COVID-19 patients [46]. Several reports identified an increased expression of exhaustion and inhibition-associated markers in circulating T cells such as CD39, CTLA4, LAG3, NKG2A, PD-1, and TIM3 [47].
In summary, these results indicate an expansion and overactivation of CD4+ and CD8+ T-cells that could lead to unresponsiveness or cell death. This appears to be true since even with a highly activated profile, CD8+ T cells from COVID-19 patients have a reduced cytokine production after in vivo stimulation [41].
CD4+ T cells may have a dual role in COVID-19, reports have identified that patients with higher activation markers on CD4+ cells have a poor prognosis, and others have identified that patients with higher T helper 1 profile (Th1) present a less severe disease [46, 48]. SARS-CoV-2-specific Th1 cells have been identified, but patients with profiles associated with SARS-CoV-2-specific Th2 and Th17 response have also been identified [49]. Another investigation has also identified an increase in transforming growth factor-β (TGFβ)-producing T cells in COVID-19 patients [50]. CD4+ FOXP3+ T regulatory cells increase during the disease but suffer a reduction in critically ill patients, which could corroborate the hyperactivation of the immune system [47, 50].
The Production of Antibodies, especially SARS-CoV-2-specific IgM and IgG, have been used as a diagnostic tool for COVID-19, although the presence of virus-specific IgG antibodies does indicate viral clearance [51]. Anti-SARS-CoV-2 antibodies may block and neutralize SARS-CoV-2 and prevent COVID-19 development.
Importantly, reports have identified that asymptomatic, moderate, and severe COVID-19 present different IgM and IgG production courses and may vary in quantity. Severe COVID-19 patients produce anti-SARS-CoV-2 IgG earlier in comparison to moderate patients, and asymptomatic and mild patients produce less neutralizing antibodies in comparison to moderate and severe COVID-19 patients [52].
More importantly, serum antibody titers rapidly decay after COVID-19, with conflicting reports with antibody titers decaying after a few months post-diagnosis [53, 54]. Nevertheless, antigen-specific memory B cells [55], T cells, and other components of the immunological memory remain effective and can be detected in convalescent patients [52, 56]. As memory cells can rapidly respond upon subsequent antigen encounter (infection), some degree of long-term immunity is expected [57].
Since SARS-CoV-2 S protein is necessary for the infection, neutralizing antibodies against this protein could in theory prevent the infection [2]. Both S-protein and N-protein specific IgM and IgG increase after the infection by SARS-CoV-2 [58], with S-protein IgG having a negative correlation with inflammatory markers in COVID-19 patients [58].
COVID-19 patients present a rapid increase in SARS-CoV-2-specific IgM, IgA, and IgG, commonly observed around a week after the infection [51, 59], however, comorbidities may impact not only on the inflammatory response during COVID-19 but also antibody production, reports identified patients with human immunodeficiency virus (HIV) presenting a delayed SARS-CoV-specific IgM and IgG production [60, 61].
Several comorbidities have been described as risk factors for the progression of COVID-19 into a severe, critical, and lethal stage. The first reports have identified advanced age, systemic arterial hypertension, and Diabetes Mellitus with a higher hospitalization and severity for COVID-19 patients [62, 63, 64]. Comorbidities may influence COVID-19 severity via an increase in pro-inflammatory response, coagulatory disorders, or different ACE2 expression [65, 66, 67]. Investigations confirmed that old age, systemic arterial hypertension, Diabetes Mellitus [68], obesity [16], alcohol consumption [69], smokers and chronic obstructive pulmonary disease (COPD) [70], heart disease, liver disease and kidney disease [71], cancer [72, 73], immunodeficiencies, transplanted patients [74], and co-infections [17, 74] are in fact risk factor for severe COVID-19 and increase death risk and the presence of two or more comorbidities further increase the death risk [75]. We will review the impact of the most common comorbidities associated with poor COVID-19 prognosis and their influence on the anti-SARS-CoV-2 immune response.
The majority of the fatal cases of COVID-19 occurred in elderly individuals [76, 77]. Several facts may explain this phenomenon, such as the accumulations of other comorbidities, immunosenescence, and inflammaging.
Immunosenescence is defined as a decline in the immune system function, characterized by the reduction in qualitative and quantitative responses to infections, neoplasia, and vaccination [78]. With age, the production of naïve lymphocytes (T and B cells) is reduced, and the function of innate immune cells is weakened, therefore negatively impacting the immune response during infections [78]. Concomitantly, the elderly develop a chronic low-grade systemic inflammation, named inflammaging.
The low-grade pro-inflammatory state is characterized by the increase in serum inflammatory mediators, such as C-reactive protein, IL-1, IL-6, and TNF [79, 80], which is associated with an impaired and dysregulated immune response.
In summary, accumulations of other comorbidities such as systemic arterial hypertension and Diabetes Mellitus, immunosenescence, and inflammaging present in elderly patients are likely to contribute to the poorer outcome in COVID-19 [81].
Systemic Arterial Hypertension is common among hospitalized COVID-19 patients and is associated with higher severity of the disease and mortality [15, 82, 83]. The initial hypothesis for this was that Systemic Arterial Hypertension and the drugs commonly used for its control, like renin–angiotensin–aldosterone system (RAAS) inhibitors that increase expression of ACE2, increasing the susceptibility to SARS-CoV-2 [68]. However, a recent report has not identified an association between the use of RAAS inhibitors and increased severity or death in COVID-19 patients [84].
Other explanations are related to the modulations of ICAM and E-selectin, which are increased in systemic arterial hypertension and can be downregulated by dexamethasone [85, 86]. Dexamethasone treatment during COVID-19 can reduce the death rate in patients receiving both invasive and non-invasive mechanical ventilation [87]. Although no investigation on the modulation of ICAM and E-selecin has been performed, these results further support that the reduction of inflammation during COVID-19 can improve the patients’ outcome [87].
Diabetes Mellitus (DM), obesity, and metabolic syndrome increase the levels of circulating pro-inflammatory cytokines in comparison to lean people. This low-grade inflammation is lower than individuals with infections but can influence cellular metabolism and immune response [88, 89]. Obesity affected the frequency and ratio of CD8+ and CD4+ T cells, inducing an increase in inflammatory macrophages [90] and reduces the frequency of T regulatory cells, therefore favoring a more pro-inflammatory profile [91]. In obesity, there is a great increase in memory T cell in the adipose tissue, that upon infection can generate pancreatitis, and increase mortality [92]. Similar to inflammaging, obesity is also characterized by low-grade inflammation, with an increase in the production of chemokines and cytokines by the adipose tissue [92]. Obesity is also associated with several risk factors for COVID-19 such as respiratory dysfunctions, type 2 Diabetes Mellitus (DM2), and hypertension [16].
The type of Diabetes Mellitus is rarely described in COVID-19 investigations [93]. A recent investigation compared the mortality rate among type 1 Diabetes Mellitus (DM1) and DM2 patients during SARS-Co-V-2 infection. The unadjusted mortality rate per 100 000 was 27 for non-DM, 138 in DM type 1 (DM1) and 260 in DM2, the adjusted data verified that the odds ratios of COVID-19-related deaths were 3.51 in DM1 and 2.03 in DM2 [94]. Concluding that both DM types present a greater risk of death by COVID-19 [94].
An important factor is that poor glycemic control can influence the disease course [95], this is supported by several manuscripts that described the deleterious effect of elevated blood glucose levels on the immune response to COVID-19 and DM2 patients with better glycemic control presented a lower death rate in comparison with COVID-19 DM2 patients with hyperglycemia [96, 97, 98]. Diabetic patients also present a low-grade inflammation with an increase in pro-inflammatory cytokines and reactive oxygen species, but an impaired inflammatory response to microbial products [99, 100].
Non-diabetic patients with COVID-19 can also present hyperglycemia [15], and is associated with an increased incidence of severe illness and death risk [101]. Several drugs used for the control of inflammation can modify or induce hyperglycemia during COVID-19 hospitalization [102], which could affect the anti-SARS-CoV-2 immune response. A few manuscripts have hypothesized COVID-19 causes alterations of glucose metabolism, via direct SARS-CoV-2 infection of the pancreatic beta cells [103, 104]. Importantly, metabolic alterations have been described in COVID-19 patients, with and without DM, developing ketosis and ketoacidosis [105]. In a case report, a 29 years old patient, non-DM with a normal glucose level was diagnosed with COVID-19. Two weeks after recovered from COVID-19 was diagnosed with DM1 [106].
Therefore, COVID-19 may also represent a risk factor for the development of DM. A related point to consider is that DM patients may have long-term consequences from COVID19, with an increase in the need for daily insulin [107]. Currently, there is no explanation for this phenomenon, but COVID-19-mediated gastrointestinal dysbiosis could be a factor since the microbiota can influence the development or aggravate metabolic disorders [108]. Also, metformin, a drug commonly used by DM2 patients, may cause alteration on the gut microbiota and impact their anti-SARS-CoV-2 immune response [109, 110].
Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide. COPD is characterized by progressive and irreversible airflow limitation due to structural alterations on the small airways. Smoking is the leading cause of COPD, due to the increase in inflammation and pulmonary remodeling [111]. Smoking and COPD are known to increase the risk for respiratory infections [112, 113]. Smokers and COPD patients have been identified among hospitalized COVID-19 patients since early reports [83]. COPD and smoking have been associated with an increased incidence, severity, and poor prognosis in COVID-19 [70, 114, 115, 116].
A common component in tobacco cigarettes and electronic smoking devices is nicotine, which can downregulate Interferon regulatory factor 7 and curb antiviral immune response [117]. COPD patients have a reduction in the expression of type I and type II interferons, and interferon-stimulated genes, therefore having a reduced antiviral response resulting in frequent respiratory exacerbations [118].
Other mechanisms postulated for the increase in susceptibility among those patients are the increase in lung inflammation and oxidative stress [119] and increase in the expression of the ACE2 receptor, SARS-CoV-2 entry receptor, in COPD and Smokers [120].
Interestingly, allergic asthma characterized by a Th2 immune response, with increased production of IL-4, IL-5 and IL-13, is associated with a reduction of the expression of ACE2 receptor [65]. And asthma is associated with a reduction in the severity of COVID-19 [121, 122]. It is important to highlight that non-allergic asthma or neutrophilic asthma increases the production of IL-17 in the lungs, which increases ACE2 expression, therefore possibly increasing the risk for severe COVID-19 [123].
Other respiratory diseases such as bronchiectasis, sarcoidosis, idiopathic pulmonary fibrosis, and lung cancer are also associated with an increase in COVID-19 severity, but further investigations are needed to understand the immune mechanism [124].
Since asthma, smoking and COPD are also commonly associated with other comorbidities, this could further increase the COVID-19 severity and death risk in these populations [125, 126].
Cancer patients are regarded as more vulnerable to severe COVID-19, due to the direct immunosuppression caused by the tumor or indirectly by the antitumor treatment [127, 128]. Patients with hematological malignancies, such as leukemia and lymphoma, have an exacerbated cellular proliferation with a reduction in the immune response, increasing the susceptibility to infections [129].
Location and cancer stage can also impact COVID-19 development. A recent report among patients with cancer identified that lung cancer, gastrointestinal cancer, and breast cancer are the most common [130]. Patients with stage IV cancer also account for a high number of COVID-19-infected patients [130, 131]. Cancer patients with COVID-19 also have an increase in hospitalization duration and severity [130, 131].
In addition to immune suppression, hospitalized cancer patients or patients undergoing frequent hospital visits may be at great risk for SARS-CoV-2 infection, increasing the necessity for precautionary measures [132, 133].
Immunodeficiencies are uncommon and chronic disorders of the immune system, that hinders the ability to develop an appropriate immune response, leading to deficient, exacerbated, or absent response to an infection or disease [134]. The immunodeficiency can be localized in any cell or structure of the immune system, compromising barrier immunity, innate immunity, or adaptive immune.
Immunodeficiency disorders can be divided into primary and secondary immunodeficiencies. Primary immunodeficiencies are a consequence of genetic defects, and secondary immunodeficiencies are caused by external or environmental factors, such as nutritional disorders or HIV [135].
The most common primary immunodeficiency is the common variable immunodeficiency that affects the patients’ ability to mount an appropriate humoral response during infection [136]. These patients are commonly treated with immunoglobulin replacement [137]. A recent case report identified a patient with common variable immunodeficiency and severe COVID-19, that was successfully treated with COVID-19 convalescent plasma [138]. Although it is important to highlight that convalescent plasma treatment has controversial results, even when applied at the beginning of the infection and with high titers of neutralizing antibodies [139, 140, 141].
Reports of patients with primary and secondary immunodeficiencies identified an increase in severity and mortality due to COVID-19 in these patients in comparison with available data on COVID-19 [142, 143]. Also, patients with immunodeficiencies can present other comorbidities, further increasing the death risk by COVID-19 and increased risk for the development of secondary infections during hospitalization [142, 143]. Certain immunodeficiencies compromise specific anti-viral immune responses, for example, TLR7 gene defect, with compromised type I and II interferon production, are linked to severe COVID-19 in young individuals [144].
A common secondary immunodeficiency AIDS, the one caused by HIV, can compromise the anti-viral immune response during COVID-19. Patients with low CD4+ count have a higher severity and mortality risk compared with patients with normal CD4+ count [145]. In patients with HIV viral suppression, other comorbidities may increase patients’ death risk during COVID-19 [30, 145].
Bacteria and viral co-infections and secondary infection in COVID-19 patients are important factors in the patients’ treatment and outcome [146]. Co-pathogens included bacteria, fungi, parasites and viruses can modulate patients’ immunity and also curb the anti-SARS-CoV-2 immune response [146]. Patients with invasive mechanical ventilation are at greater risk for bacterial co-infections [17, 147], also several patients report diarrhea without gastrointestinal SARS-CoV-2 infection, which could be a secondary gastrointestinal infection or microbiota dysbiosis [108].
Co-infections can increase the susceptibility to severe COVID-19, by an increase in the hyper inflammation or hypercoagulation status [74, 148]. Few reports have investigated the impact of parasites on COVID-19, such as leishmaniasis, toxoplasmosis, malaria, and Chagas disease [148, 149, 150, 151]. Clinical manifestations of those diseases are usually associated with an increased and unregulated type 1 pro-inflammatory response, similar to COVID-19 [151]. In fact, a few case reports identified that chagasic patients with COVID-19 present an exacerbated inflammatory response, with a high lethality [74, 148]. This represents a further difficulty in the treatment of COVID-19, since the combination of drugs for the treatment of COVID-19 and the co-infections, the immune response to the co-infections and possible comorbidities need to be equated.
COVID-19 vaccines are currently the only prophylactic/curative treatment for COVID-19, since drug repurposing and monoclonal antibodies trials had limited success, and investigations with convalescent plasma have conflicting results [87, 139, 140, 141, 152, 153]. Several vaccines are currently developed and in developing. Due to the high demand for a COVID-19 vaccine, significant advances in vaccine technologies have been made in the last year. Currently, 3 types of vaccines are being administered worldwide: inactivated virus vaccines (IVV) [154], vaccines that use mRNA with lipid nanoparticle (LNP) delivery systems [155], and vaccines containing DNA delivered within non-replicating recombinant adenovirus (AdV) vector systems [156]. AdV and mRNA vaccines aim to induce the production of SARS-CoV-2 S protein and induces the production of neutralizing antibodies [139, 141, 153].
All vaccines can induce the recognition of the viral antigen (immunogen) and also serve as an adjuvant to boost the immune response, the immunogen is recognized by innate immunity receptors such as toll-like receptors 3 and 7, RIG-I, and NOD2 inducing cellular activation and the production of interferons. This process will also induce the migration of DCs to secondary lymphoid organs and prime SARS-CoV-2-specific T cells [139, 141, 153]. Further questions regarding the effectiveness of vaccines are still going to be investigated, especially the long-term immunity and efficacy against new variants.
COVID-19 is a hyperinflammatory and hypercoagulation syndrome, with a hallmark increase in inflammatory mediators such as C-reactive protein, creatinine, urea, cytokines, and chemokines in the blood, with an increase in the neutrophil count and reduction in lymphocyte and platelet count. These processes lead to a dysregulated immune response that can be lethal. The overall mortality ratio is still unknown but is higher in patients with comorbidities. Patients with common and rare comorbidities may present differences in the immune response in comparison to healthy individuals.
The COVID-19 pandemic is a hallmark of world history, this systemic disease killed millions, raised ethical dilemmas, and put science and immunology on the daily lives of millions worldwide. Immunological investigations have helped the development of treatments and vaccines for this disease, but many questions are still left to be answered. The current knowledge is limited, but never in the previous history so many researchers around the world were focused on investigations on one disease. Several technologies developed and tested during this pandemic may bring light to other diseases, such as the new technologies in vaccine development and treatments.
Ricardo Wesley Alberca has a fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Grant Number: 19/02679-7.
The SYNTHESIS PoP has emerged from the aggregation of three digital platforms that have been developed at the Integrated Systems Laboratory (ISL) over a period of seven years in the context of DICE (Digital Immersive Cultural Environments), a concept and architecture of a comprehensive ecosystem for the promotion of digital cultural experiences introduced by the author in 2014 and detailed in his publication, alongside with his research team at the Media Art Innovation (MAI) Unit of ISL, in 2016 [1]. The three building blocks of SYNTHESIS, namely the platforms SYNTELESIS/iGuide, AFIGISSI (Narration), and wayGoo, have been described as stand-alone platforms in the references [2, 3, 4, 5, 6, 7, 8, 9] (in Greek), and in [10, 11, 12].
SYNTHESIS PoP aspires to create a unified digital environment for the coherent creation, management, editing, and visualization of digital material related to cultural heritage artifacts (monuments, museums, museum exhibits, art exhibitions), and the development of personalized interactive narrative experiences using mobile and VR/AR technologies for visitors to places of cultural interest.
The SYNTHESIS PoP aims to offer tools for managing a large volume of digital material, supporting various forms of digital content, such as text, images, video, audio, 3D objects, BIM objects, Unity scenes, etc., and covering a wide range of available material. These building blocks, combined with recorded stories and information, will be interconnected to compose digital exhibits that will be converted into digital experiences, either in-situ through mobile and AR technologies, or remotely through VR technologies.
SYNTHESIS will contribute to the creation of a new condition for the promotion of cultural heritage sites or museum exhibits and facilitate the management and interaction of the user/visitor with them, and the overall user experience. The PoP will results in an innovative environment for the integrated management of a large volume of digital material, the creation of narrative experiences related to digital exhibits for visualization in physical and virtual spaces, and consequently the promotion of cultural heritage by supporting: (a) the production of digital content; (b) the linking of digital content to additional multimedia digital material related to said content, such as relevant data relating to the process used for creating digital content, relevant digital and digitized audiovisual material, recorded stories and information relevant to the context of the subject matter and narrative used as the basis of creation; (c) the designing and curating a narrative flow for a deeper understanding of the content associated with the subject of an exhibition of digital material, both virtual reality and physical space, by visitors and end users; and (d) the transformation of the curation outcome into experiences for in-situ and/or distance visualization capable of mobilizing both tourist and social interest in the importance of the cultural heritage as a holistic educational-educational experience and the need for its preservation and promotion, Figure 1.
Curation of digital objects, creation of digital experiences through narration, and visualization with virtual and augmented reality technologies and mobile apps [
In the context of a digital experience (be it at a natural exhibition or museum, an archeological space, a virtual space, or a hybrid environment), it is possible to connect the digital exhibits semantically and thematically digital exhibits to a physical or virtual exhibition, museum, or archeological site, through the use of graphs and graph databases (Figure 2). In this process, the content reporting platform wayGoo [10] is used to visualize the georeferenced narrative in an easily to understand way in a physical, virtual, or hybrid reality space.
Using graphs and graph databases for seamless digital content interconnection and digital narrative creation.
The easy understanding of the content by the end user in the context of a narrative is achieved through the transformation of the narrative into an immersive interactive experience capable of being consumed by common mobile tablets and smartphones using AR technologies in the exhibition/museum space/archeological site, Figure 3a, as well as through more integrated solutions such as VR headsets and/or projection imaging technologies for remote experiences in virtual space, Figure 3b. A narrative can be created by artists and people in the field of culture, using an accessible and friendly graphic environment. Storytellers will not be required to possess advanced and specialized knowledge of the underlying technologies used to implement it.
(a) In-situ experience through AR. (b) Remote experience through VR technologies.
SYNTHESIS is accompanied by two applications available for use by the public (Figure 4).
An augmented reality application for mobile devices that offers possibilities of interactive exploration of an exhibition and consumption of all available digital material associated with it as an immersive storytelling experience during the physical presence of the user in situ.
A virtual reality application that allows the interactive exploration of an exhibit remotely and the consumption of rich 3-dimensional models and interactive scenarios with realistic graphics directly from a VR-enabled device.
VR/AR applications of the SYNTHESIS PoP to be used by the general public for immersion experiences.
The SYNTHESIS PoP also offers advanced tools based on artificial intelligence (AI) and natural language processing (NLP) techniques to assist the discovery of contextual correlations between digital content, digitized assets, and digital artifacts and exhibits [13, 14]. By analyzing the structural elements of the exhibits alongside with all known connections among them, the system identifies possible undiscovered correlations and provides a multimodal and user-friendly representation and visualization of the results. AI and NLP tool and technologies are also used to implement a system of personalization and personalization of the experience in accordance to the user preferences. The personalization system recommends relevant exhibits and narratives based on user interests, in order to maximize the in-depth understanding of the content of the narrative associated with the curated experience in accordance with the curation and visualization approach of the digital content curator.
Finally, using blockchain technology, it is possible to implement smart contracts to control the use of digital content by its creator, and to track the ways of its utilization. This will safeguard the integrity of the digital content and protect the copyright and financial rights of its creator, Figure 5.
Schematic representation of the SYNTHESIS of platforms with blockchain functionality.
In summary, the main goal of the SYNTHESIS PoP is to contribute to the promotion of cultural heritage items and places of cultural interest to a global audience by visualizing the results of recording and research with VR/AR technologies and the possibility of interactive and personalized experience of the relevant content. situ and/or remotely. It also aims to highlight the work of artists and people in the field of Culture, and to promote culture to the public through tools to create innovative and engaging experiential experiences using cutting-edge technologies. It will offer visualization of an exhibition through personalized interactive narrative experiences of virtual and augmented reality (VR/AR) and the georeferencing of its individual exhibits in places of cultural interest (art exhibitions, museums), allowing the creation of educational and educational experiences, the mobilization of tourism and social interest, and the preservation, promotion, and curation of its exhibits. In Figure 6, we give an example of using the wayGoo platform [9] to visualize an interactive experience of digital representations of cultural treasures from the Minoan palace of Phaistos in Crete created with the help of the SYNTELESIS platform by the Integrated Systems Laboratory with the use of digital immersion technologies, such as content geo-reporting (wayGoo), AR/VR, and 2D/3D animation.
Example of using the wayGoo platform to visualize an interactive experience at the palace of Phaistos in Crete, Greece.
Additional objectives of the SYNTHESIS PoP include:
The further promotion and editing of cultural heritage items through the visualization of the results of recording and research and the creation of complex digital objects.
The promotion of the work of artists and people in the field of Culture, and the promotion of areas of cultural interest, and the promotion of culture at large to the public, through the provision of tools for creating innovative and attractive mixed-reality experiences using cutting-edge technologies.
The transfer of know-how on and the experience from research and development of state-of-the-art products from research centers and professional researchers to start-ups through dissemination of knowledge and networking, to assist them generate profit, develop human resource skills, and attract new and supporting extroversion and competitiveness.
The creation of new jobs in the creative industry and the provision of intellectual property and rights, including financial, for creators through smart contracts and integration of blockchain technology in the SYNTHESIS PoP ecosystem [1].
The SYNTHESIS PoP seeks to strengthen the activity in the field of Culture, Tourism and Creative (CTC) Industries, in terms of the production of digital content (entertainment, educational, cultural, commercial or other interest), and the organization of big scale activities and events. The PoP and user applications are expected to be marketed either as separate products or as a single system. The architecture and modular system of the platform, as described by its main components (wayGoo, NARRATION, iGuide VR/AR component), allows future adaptation to content and requirements of different organizations. The modularity of the SYNTHESIS PoP allows to accommodate different markets and different players in the CTC Industries in the SYNTHESIS ecosystem in a way that is expected to lead to maximizing market penetration and benefits for the constituencies of the ecosystem by enabling the efficient management of digital content, the facilitation of the conversion of digital content into experiences, and the protection of IPRs and profit flows through blockchain and smart contracts.
The adoption of the SYNTHESIS PoP is expected to lead to the following benefits in each one of the five (A, B, C D, and E) sectors of the DICE Ecosystem, Figure 7.
Facility of specialized users in the design and editing of large-scale interactive experiences, through a narration tool that allow easy and creative workflow.
Creation of a perfect product, developing with scientific methodology and dynamic commercial presence.
Strengthening the technological base, gaining a technological lead in the field of production and supervision of interactive producers, which sets the specifications for the expansion of the developing platform.
Enhancing innovation and competitiveness in the field of artistic curation. Internationally, there is no system that provides a complete solution for large-scale interactive events.
Opening to new national and international markets. Penetration in the market through the possibility of highlighting and reusing places of cultural interest: Museums, Art Galleries, Archeological sites, preserved Industrial sites etc.
Strengthening cultural tourism by increasing the tourists’ interest in visiting cultural sites as a result of upgrading their on-site experience, but also through a strategy of diffusion of the results of the implemented activities.
Strengthening the networking of cultural organizations through the creation of business networks with the cultural and creative industry for the joint promotion of the innovative products of the project.
Improving the productive potential of digital technology and digital content companies.
Approach of new markets in the field of culture and tourism, inaccessible until today, through their activity in designing interactive audiovisual content.
Utilization of research for the development of market-oriented solutions, through the conversion of the research product into a commercial product. Added value that results through innovative interventions and interdisciplinary cooperation, in order to create a final product that promotes Greek tourism and culture.
Distribution of research results to the general public, through the commercial product but also through presentations at conferences.
Improvement of the user experience and enrichment of the means of receiving the artistic/creative result, through his active participation in the interaction in natural and virtual space.
Promoting cultural spaces through the implementation of technologically and artistically perfect cultural events and enhancing the interest of the general public for them.
Promoting the collaboration of artists with audiovisual events.
The digital immersive cultural environment (DICE) ecosystem [
The SYNTHESIS PoP is expected to act as a catalyst in the articulation of a digital creativity ecosystem for enabling the creation of DICE (Digital Immersive Cultural Environment) [1], Figure 7. The incorporation of smart contracts and blockchain technology in SYNTHESIS is expected to stimulate the process of crowdsourcing digital artifacts, narratives, and experiences alongside with their visualization, from professionals, as well as qualified non-professionals, in the fields of art, culture and creativity. The embedded protection of the Intellectual Property Rights (IPRs) of the digital creator build in SYNTHESIS, and the use of blockchain-enabled Smart Contracts to speed up the contracting and outsourcing process, track revenue streams form the use or sales of digital content, and protect the agreed upon revenue sharing with the creators of the digital content, narrative and experience, are expected to spearhead the process of digital creativity across the entire digital creativity ecosystem as shown in Figure 8.
Enabling digital creativity ecosystem for the creation of digital immersive cultural environments (DICE) [
The SYNTHESIS PoP aims to create a coherent platform for the creation of advanced digital assets, the curation of digital objects and their semantic and thematic interconnection through the creation of narratives, and the creation of digital experiences in virtual and real space through the georeferencing of edited digital content and related storytelling, with a range of virtual and augmented reality technologies using tablets, smartphones, virtual reality glasses, and projection imaging technologies.
The SYNTHESIS PoP is based on the coherent integration of existing platforms, services, algorithms, and applications that have been developed in the Integrated Systems Laboratory (ISL) and their effectiveness has successfully been evaluated. The timely and effective accomplishment of SYNTHESIS objectives is largely ensured through the validation of the existing know-how and the possibilities of adopting it in developing solutions for other use cases, similar ot completely new. Technological solutions already developed will be adapted to new requirements and tools already available will be leveraged, adapted as required, and integrated in a coherent SYNTHESIS PoP.
The three platforms SYNTHESIS PoP is made up of, namely wayGoo, SYNTELESIS and AFIGISSI (Narration), are briefly describe in the following. All three platforms have been developed in the Integrated Information Systems (ISL) Laboratory of the Institute of Informatics & Telecommunications at NCSR “Demokritos” through a series of funded projects that are described in the publications [1, 2, 3, 4, 5, 6, 7, 8, 9, 10] and acknowledged at the end of the Chapter. The three platforms are:
Access to the narratives is possible either during the physical visit to the infrastructure during their regular operation and in extraordinary, periodic or temporary events or remotely. Traditional narrative practices address the development of narrative by placing objects on a linear axis. Instead, the work highlights cultural content with new narrative structures, operating with less strictly prescribed scenarios. In fact, according to new media theorist L. Manovich [17], the database is generally the way to tell a story today. The creation of narratives is achieved in an automated and semi-automated way, by reversing the time axes and with a variety of thematic grouping options, making a theoretically infinite number of combinations [18], in order to respond to modern perceptions of object multiplicity and the possibility of multiple interpretations. Personalization is done both for individual users and for groups of users who work together to create a narrative. According to the current level of collaborative platform technologies, there are possibilities to connect multiple users for the purpose of a common task [19]. The system allows specialized and non-specialized users to produce stories of various sizes based on the content available and share them with the public. The aim is a holistic approach to storytelling that will lead to mature technology and an innovative tool aimed at the market for (a) the design and implementation of digital collection management software platforms for cultural operators, and (b) web applications, mobile and VR/AR applications for organizations of digital exhibitions and creation of narratives from a registered collection of museums and other cultural exhibits.
In the SYNTHESIS PoP, the three building-block platforms are redesigned, expanded, and integrated into a single controllable and coherent digital creativity environment with the addition of blockchain technology for the protection of IPRs and the introduction of smart contracts for the facilitation of signing contracts for the creation of digital assets, content, context, and experiences, and the verifiable of equitable sharing of revenue streams across the entire creativity chain involved in the creation and visualization of digital experiences, Figure 9.
Schematic representation of the main structural elements of the SYNTHESIS platform.
Figure 8 depicts the Implementation Architecture of the SYNTHESIS PoP. In the architecture, there are three distinct layers: The Data layer, the Business Logic layer, and the Presentation layer. Each layer is made up of various components as indicated in the infographic of Figure 10.
The
(interfaces with) third party databases;
innate to SYNTHESIS databases, such as mongoDB, Neo4j, PostgreSQL, …;
a repository of digital assets; and
a blockchain module for the protection of IPRs and the support of Smart Contracts.
The
an Application Programming Interface (API) that allows users and end users of the PoP to interface with SYNTHESIS through either
the Web Portal for the production, curation, management of digital content and the creation of experiences, or
the Visualization Applications (mobile and VR/AR);
A Back-end Support System (docker) for dockerizing content;
an AI (Artificial Intelligence) component that consists of two modules:
a Content Management System based on Natural Language Processing (NLP) to support contextual and semantic correlations and AI algorithms and applications, and
a Personalization and Recommendation system alongside a variety of statistical, fuzzy and AI based processing algorithms, to support user-tailored digital experiences of the curated digital material and narratives.
The
a User Interface (UI) in the form of a Web Portal that allows to:
Insert Digital Content in SYNTHESIS, and
Manage Digital Content in PoP;
User Experience (UX) through End User Applications that include:
mobile apps for both Android and iOS smartphones, and
VR/AR technologies for a variety of portable platforms and devices.
Implementation architecture of the SYNTHESIS platform of platforms.
Moreover, the SYNTHESIS PoP architecture and the accompanying applications support the following:
Enrichment of support and management of geo-reported data related to natural areas, together with services for the consumption of this information with GIS/Tile services.
Improving the determination of geographical location indoors to facilitate indoor navigation with the use of existing know-how from the implementation of a Bluetooth Beacons infrastructure developed in the context of the European funded projects FlySEC, http://fly-sec.eu/ [20] and TRESSPASS https://www.tresspass.eu/The-project [21].
End users can consume the digital content of the platform through a mobile application. The application can be used: (a) either during the physical presence of the user in an exhibition, where is guided in the tour of the exhibition, taking into account user priorities, or (b) remotely, where the user is guided to explore the exhibition and delve into the digital content that the platform provides. Using GPS technologies and/or Bluetooth beacons, the application can locate the user physical location, suggest relevant exhibits and narratives, and assist in exploring and navigating the area. Users can locate exhibits and places of interest through an interactive map, from a list through a narrative, by scanning their own QR code, or through a search with free text which is interpreted lexically and semantically by the back-end AI module. Information about the exhibit is then presented, accompanied by its correlations with other exhibits, narratives, dates, and natural sites. Finally, it is possible to view 2D/3D models directly from the device, as well as play accompanying multimedia material in the form of images, videos, panoramic images, and sounds [7, 8, 9].
Improving the process of creating narratives and their representation using graphs, as well as the general management of digital content and repositories [2, 4, 5].
Design and development of Blockchain infrastructure for the use of smart contracts. To preserve the integrity of each element and to track the ways of its utilization, SYNTHESIS utilizes blockchain technology. This technology forms the basis for creating an unchanging event log. This file through the security properties of Blockchain will provide a high degree of protection of data integrity as well as their continuous availability. Within the SYNTHESIS PoP, the blockchain will record the interfaces between nodes of the graph as well as the changes in these interfaces. In addition, it will store metadata and metadata related to digital data as well as record which users of the “SYNTHESIS” platform utilize each component. Additionally, blockchain will record information about derivative projects that utilized a digital component as well as project location data in both physical and virtual exhibitions. The above functions make it possible to use the smart contracts executed on the blockchain. Smart contracts will allow creators to control which users (creators or curators) will be able to use the digital data they have created and for what purpose. Finally, smart contracts enable any interaction (e.g., data entry) with the blockchain.
SYNTHESIS allows the establishment of correlations between different narrative elements (recommendation process) enriched with audiovisual material if required [13], and offers personalization services and personalized functions [10]. Based on the categorization of the narratives and the corresponding evaluations by the users of the application, machine learning and automatic classification techniques are applied to identify similarities between the narratives and their individual structural elements. These similarities are multi-layered, reflecting similarities that are based on the preferences of the users but also based on the content, and are determined conceptually and lexically, after processing natural language from any descriptions/tags/categories that accompany each narrative and each structural element. In addition, where possible, from each element, depending on its format (audio file, image, video, text), additional metadata/features are extracted using deep machine learning techniques. The additional metadata/features represent each object based on its components (e.g., color choices and image contrasts, rhythm/style of music, etc.). Through correlations with the respective user ratings, similarities are calculated in greater depth allowing the discovery of new correlations and features that determine user preferences. The result is a multidisciplinary graph that represents the narratives and objects, and the similarities between them at all the levels of similarity considered [11].
With the aim of visualizing different types of experiences, the SYNTHESIS PoP supports the visualization of digital content of various types and formats (2D/3D) through a virtual reality application for mobile devices and VR headsets. Content can come from 3D modeling tools, e.g., Building Information Management (BIM) objects, or gaming machines, e.g., interactive experiences in 3D environments, (https://vimeo.com/isldemokritos). Each type of content offers different possibilities and therefore it is necessary to support all types of 3D content. The visualization of rich 3D experiences is realized with a user-centric approach [17, 18, 19] and through a (separate) application implemented in the Unity game machine and provides the possibilities of 3D visualization and navigation. The wayGoo application opens the Unity application and loads the corresponding experience by downloading the corresponding Unity asset bundle from the platform. Communication between the two applications can be implemented with mobile URL schemes that allow the use of parameters when opening applications [12].
The three platforms SYNTHESIS is based on, namely iGuide/SYNTELESIS, Narration/AFIGISSI, and wayGoo have been tested in different use cases, environments, and applications as pilot tests. Below we make reference to three such use-case scenarios by summarizing the use case environment, the scenario used and the targeted audience and objectives.
The developed solutions in the three use case pilot test scenarios aimed at analyzing the of SYNTHESIS and the three platforms within it, in terms of the efficiency and effectiveness of creating immersive experiences in the context of DICE. The three carefully selected use cases demonstrated the ability of SYNTHESIS, and the three platforms is made up of, to create:
In March 1900, on the Greek Island of Crete, Arthur John Evans, a British archeologist, unearthed what he called the Minoan Civilization; a colorful world that seemed forgotten by time. A blend between reality and imagination, the reconstruction of the Palace of Knossos has become an iconic symbol of the past, triggering endless debates and providing a rich canvas for creative reconstructions.
iGuide Knossos is a HD/3D VR reconstruction of the Knossos Palace that merges Evans’ vision of the site with contemporary archeological evidence. It is meant to be used as a VR edutainment environment, providing a fertile ground for future development of educational, entertainment and action games such as Fruzzle, Knosseau and Knossos Labyrinth (thumbnails provided), which are using the Minoan civilization and myths as a foundation for their action play.
iGuide Knossos is a HD/3D VR reconstruction of the Knossos palace.
Floor plans and drawings: Levi, D., 1976. Festos e la Civilta Minoica I, Rome: Ediz.dell’Ateneo. 3D modeling and application of materials [
The
a. Digital curation example using the AFIGISSI platform: Conceptual depiction of the transitioning: (a) from museum exhibits to digital assets, (b) from digital assets to digital exhibits, (c) from digital exhibits to digital narratives; and (d) from digital narratives to exhibits and their visualization with smartphones and VR/AR as in
An audiovisual projection mapping installation inspired by the world of Knossos and its digital interpretation and constitutes a blueprint for the creation of an immersive digital experience (Ariadne’s Journey) from 3D digital assets and animations created within iGuide Knossos for the reconstruction of the ancient Minoan Palace of Knossos in Crete, Greece, an original narrative that addresses the process of knowledge discovery through excavations of historic monuments, and history itself, by a young contemporary girl, and the visualization of the outcome of this curatorial effort with VR technology and projection mapping [5, 25]. The narrative, artistic and spiritual field of Ariadne’s journey explores the construction of memory and the meeting points of the historical and mythological constructions that experience the unexpected journey of a young modern heroine. Through esthetic narrative, the work aims to create an experience for listeners of all ages, translating, or perhaps more accurately, the interpretation of CH images and historical documentation into a living esthetic vocabulary, Figure 14 [23].
Ariadne’s Journey concerns an audiovisual projection mapping installation, inspired by the people of Knossos. Ariadne leaves the city behind to discover a fantasy world, created from familiar and strange images, where the myth, the archaeological hoe and the dreamy mood are intertwined in a colorful fantasy puzzle. Ancient ruins are transformed, frescoes come to life [
In this chapter an extended description of the SYNTHESIS Platform of Platforms (PoP) has been given. The architecture and the three platforms SYNTHESIS is based on are described in detail. SYNTHESIS results from the integration of the three platforms iGuide, Narration (Afigissi), and wayGoo, in a coherent environment that allows the seamless creation of augmented digital assets, their management and curation in the context of a narrative, and the creation and visualization of digital experiences with mobile applications and VR/AR technologies. SYNTHESIS is the outcome of an over a decade research and development at the Integrated Research Laboratory at NCSR Demokritos towards the development and implementation of the Digital Immersive Cultural Environment (DICE) concept. Examples of three different digital immersive experiences that have been developed as DICE applications to demonstrate the capabilities of SYNTHESIS as PoP for creating digital experiences, have been given. SYNTHESIS supports blockchain and smart contract technologies that are used to protect IPR’s and enable smart contracts to safeguard the use of digital content and encourage the creation of new digital content, its curation and distribution by protecting the IPR’s of the creators and honoring contractual obligations and revenue streams agreed upon between creators of digital experiences and distributors of these experiences,
The research described in this paper has been supported by the following research contracts:
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Tunisia",slug:"role-of-the-ne-sw-hercynian-master-fault-systems-and-associated-lineaments-on-the-structuring-and-ev",totalDownloads:8150,totalCrossrefCites:17,totalDimensionsCites:26,abstract:null,book:{id:"2227",slug:"tectonics-recent-advances",title:"Tectonics",fullTitle:"Tectonics - Recent Advances"},signatures:"Fetheddine Melki, Taher Zouaghi, Mohamed Ben Chelbi, Mourad Bédir and Fouad Zargouni",authors:[{id:"39860",title:"Dr.",name:"Taher",middleName:null,surname:"Zouaghi",slug:"taher-zouaghi",fullName:"Taher Zouaghi"},{id:"147368",title:"Dr.",name:"Fetheddine",middleName:null,surname:"Melki",slug:"fetheddine-melki",fullName:"Fetheddine Melki"}]},{id:"30707",doi:"10.5772/29917",title:"Radon as Earthquake Precursor",slug:"radon-as-earthquake-precursor",totalDownloads:3763,totalCrossrefCites:11,totalDimensionsCites:20,abstract:null,book:{id:"2051",slug:"earthquake-research-and-analysis-statistical-studies-observations-and-planning",title:"Earthquake Research and 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Gökten",authors:[{id:"140276",title:"Dr.",name:"Akın",middleName:null,surname:"Kürçer",slug:"akin-kurcer",fullName:"Akın Kürçer"},{id:"144563",title:"Prof.",name:"Yaşar Ergun",middleName:null,surname:"Gökten",slug:"yasar-ergun-gokten",fullName:"Yaşar Ergun Gökten"}]}],mostDownloadedChaptersLast30Days:[{id:"64562",title:"Electrical Resistivity Tomography: A Subsurface-Imaging Technique",slug:"electrical-resistivity-tomography-a-subsurface-imaging-technique",totalDownloads:3141,totalCrossrefCites:7,totalDimensionsCites:9,abstract:"Electrical resistivity tomography (ERT) is a popular geophysical subsurface-imaging technique and widely applied to mineral prospecting, hydrological exploration, environmental investigation and civil engineering, as well as archaeological mapping. This chapter offers an overall review of technical aspects of ERT, which includes the fundamental theory of direct-current (DC) resistivity exploration, electrode arrays for data acquisition, numerical modelling methods and tomographic inversion algorithms. The section of fundamental theory shows basic formulae and principle of DC resistivity exploration. The section of electrode arrays summarises the previous study on all traditional-electrode arrays and recommends 4 electrode arrays for data acquisition of surface ERT and 3 electrode arrays for cross-hole ERT. The section of numerical modelling demonstrates an advanced version of finite-element method, called Gaussian quadrature grid approach, which is advantageous to a numerical simulation of ERT for complex geological models. The section of tomographic inversion presents the generalised standard conjugate gradient algorithms for both the l1- and l2-normed inversions. After that, some synthetic and real imaging examples are given to show the near-surface imaging capabilities of ERT.",book:{id:"8361",slug:"applied-geophysics-with-case-studies-on-environmental-exploration-and-engineering-geophysics",title:"Applied Geophysics with Case Studies on Environmental, Exploration and Engineering Geophysics",fullTitle:"Applied Geophysics with Case Studies on Environmental, Exploration and Engineering Geophysics"},signatures:"Bing Zhou",authors:null},{id:"37864",title:"Role of the NE-SW Hercynian Master Fault Systems and Associated Lineaments on the Structuring and Evolution of the Mesozoic and Cenozoic Basins of the Alpine Margin, Northern Tunisia",slug:"role-of-the-ne-sw-hercynian-master-fault-systems-and-associated-lineaments-on-the-structuring-and-ev",totalDownloads:8150,totalCrossrefCites:17,totalDimensionsCites:26,abstract:null,book:{id:"2227",slug:"tectonics-recent-advances",title:"Tectonics",fullTitle:"Tectonics - Recent Advances"},signatures:"Fetheddine Melki, Taher Zouaghi, Mohamed Ben Chelbi, Mourad Bédir and Fouad Zargouni",authors:[{id:"39860",title:"Dr.",name:"Taher",middleName:null,surname:"Zouaghi",slug:"taher-zouaghi",fullName:"Taher Zouaghi"},{id:"147368",title:"Dr.",name:"Fetheddine",middleName:null,surname:"Melki",slug:"fetheddine-melki",fullName:"Fetheddine Melki"}]},{id:"43258",title:"Speedy Techniques to Evaluate Seismic Site Effects in Particular Geomorphologic Conditions: Faults, Cavities, Landslides and Topographic Irregularities",slug:"speedy-techniques-to-evaluate-seismic-site-effects-in-particular-geomorphologic-conditions-faults-ca",totalDownloads:3013,totalCrossrefCites:8,totalDimensionsCites:19,abstract:null,book:{id:"3059",slug:"engineering-seismology-geotechnical-and-structural-earthquake-engineering",title:"Engineering Seismology, Geotechnical and Structural Earthquake Engineering",fullTitle:"Engineering Seismology, Geotechnical and Structural Earthquake Engineering"},signatures:"F. 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Galea",authors:[{id:"52181",title:"Dr.",name:"Sebastiano",middleName:null,surname:"D'Amico",slug:"sebastiano-d'amico",fullName:"Sebastiano D'Amico"},{id:"58678",title:"Dr.",name:"Pauline",middleName:null,surname:"Galea",slug:"pauline-galea",fullName:"Pauline Galea"},{id:"167864",title:"Prof.",name:"Giuseppe",middleName:null,surname:"Lombardo",slug:"giuseppe-lombardo",fullName:"Giuseppe Lombardo"},{id:"167865",title:"Dr.",name:"Francesco",middleName:null,surname:"Panzera",slug:"francesco-panzera",fullName:"Francesco Panzera"}]},{id:"64060",title:"Advance Wave Modeling and Diffractions for High-Resolution Subsurface Seismic Imaging",slug:"advance-wave-modeling-and-diffractions-for-high-resolution-subsurface-seismic-imaging",totalDownloads:1156,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Seismic modeling and Imaging for the small-scale feature in a complex subsurface geology such as salt deposit, fracture reservoir, and Carbonate is not casual because of propagated wave affected by many objects once it hits the geologic structure in the subsurface. The principal goal of newly developed seismic modeling & imaging is to get a subsurface image of structural features with greatest sharpness or resolution. Using model dataset the Sigsbee and Marmousi, we illustrate the accuracy of conventional and advance wave modeling techniques. However, in conventional a Finite difference (FD) algorithm is used to generate the data and in advanced wave modeling, the low-rank (LR) approximation is used to acquire zero-offset configuration data. A field dataset from Malaysian basin is re-processed and imaged using diffraction imaging which shows an enhancement in structural interpretation. Furthermore, the results gained from the proposed modeling and imaging approach significantly enhance the bandwidth of the imaged data. Finally, a frequency spectrum shows a recovery of low-frequency from 0 to 60 Hz which is an optimal resolution of seismic imaging.",book:{id:"8361",slug:"applied-geophysics-with-case-studies-on-environmental-exploration-and-engineering-geophysics",title:"Applied Geophysics with Case Studies on Environmental, Exploration and Engineering Geophysics",fullTitle:"Applied Geophysics with Case Studies on Environmental, Exploration and Engineering Geophysics"},signatures:"Yasir Bashir and Deva Prasad Ghosh",authors:null},{id:"37858",title:"Geodynamic and Tectonostratigrafic Study of a Continental Rift: The Triassic Cuyana Basin, Argentina",slug:"geodynamic-and-tectonostratigrafic-study-of-a-continental-rift-the-triassic-cuyana-basin-argentina",totalDownloads:3419,totalCrossrefCites:0,totalDimensionsCites:14,abstract:null,book:{id:"2227",slug:"tectonics-recent-advances",title:"Tectonics",fullTitle:"Tectonics - Recent Advances"},signatures:"Silvia Patricia Barredo",authors:[{id:"147305",title:"Dr.",name:"Silvia",middleName:null,surname:"Barredo",slug:"silvia-barredo",fullName:"Silvia Barredo"}]}],onlineFirstChaptersFilter:{topicId:"654",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,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:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. 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He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. 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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",institutionURL:null,country:{name:"India"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:4,paginationItems:[{id:"81821",title:"Pneumococcal Carriage in Jordanian Children and the Importance of Vaccination",doi:"10.5772/intechopen.104999",signatures:"Adnan Al-Lahham",slug:"pneumococcal-carriage-in-jordanian-children-and-the-importance-of-vaccination",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Streptococcal Infections",coverURL:"https://cdn.intechopen.com/books/images_new/10828.jpg",subseries:{id:"3",title:"Bacterial Infectious Diseases"}}},{id:"81813",title:"Schistosomiasis: Discovery of New Molecules for Disease Treatment and Vaccine Development",doi:"10.5772/intechopen.104738",signatures:"Andressa Barban do Patrocinio",slug:"schistosomiasis-discovery-of-new-molecules-for-disease-treatment-and-vaccine-development",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"New Horizons for Schistosomiasis Research",coverURL:"https://cdn.intechopen.com/books/images_new/10829.jpg",subseries:{id:"5",title:"Parasitic Infectious Diseases"}}},{id:"81644",title:"Perspective Chapter: Ethics of Using Placebo Controlled Trials for Covid-19 Vaccine Development in Vulnerable Populations",doi:"10.5772/intechopen.104776",signatures:"Lesley Burgess, Jurie Jordaan and Matthew Wilson",slug:"perspective-chapter-ethics-of-using-placebo-controlled-trials-for-covid-19-vaccine-development-in-vu",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"SARS-CoV-2 Variants - Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}},{id:"80546",title:"Streptococcal Skin and Skin-Structure Infections",doi:"10.5772/intechopen.102894",signatures:"Alwyn Rapose",slug:"streptococcal-skin-and-skin-structure-infections",totalDownloads:48,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Streptococcal Infections",coverURL:"https://cdn.intechopen.com/books/images_new/10828.jpg",subseries:{id:"3",title:"Bacterial Infectious Diseases"}}}]},overviewPagePublishedBooks:{paginationCount:13,paginationItems:[{type:"book",id:"6667",title:"Influenza",subtitle:"Therapeutics and Challenges",coverURL:"https://cdn.intechopen.com/books/images_new/6667.jpg",slug:"influenza-therapeutics-and-challenges",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Shailendra K. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:230,paginationItems:[{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón",slug:"juan-carlos-gardon",fullName:"Juan Carlos Gardón",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:"Catholic University of Valencia San Vicente Mártir, Spain",institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain. She is a Full Professor at the Department of Medicine and Animal Surgery at the same University. She developed her research activity in the field of Endocrinology, Hematology, Biochemistry and Immunology of horses. She is a scientific reviewer of several international journals : American Journal of Obstetrics and Gynecology, Comparative Clinical Pathology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology. Since 2014, she has been the Head of the Clinical Analysis Laboratory of the Hospital Clínico Veterinario from the Faculty of Veterinary, CEU-Cardenal Herrera University.",institutionString:"CEU-Cardenal Herrera University",institution:{name:"CEU Cardinal Herrera University",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"423023",title:"Dr.",name:"Yosra",middleName:null,surname:"Soltan",slug:"yosra-soltan",fullName:"Yosra Soltan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"349788",title:"Dr.",name:"Florencia Nery",middleName:null,surname:"Sompie",slug:"florencia-nery-sompie",fullName:"Florencia Nery Sompie",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sam Ratulangi University",country:{name:"Indonesia"}}},{id:"345713",title:"Dr.",name:"Csaba",middleName:null,surname:"Szabó",slug:"csaba-szabo",fullName:"Csaba Szabó",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"345719",title:"Mrs.",name:"Márta",middleName:null,surname:"Horváth",slug:"marta-horvath",fullName:"Márta Horváth",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"420151",title:"Prof.",name:"Novirman",middleName:null,surname:"Jamarun",slug:"novirman-jamarun",fullName:"Novirman Jamarun",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Andalas University",country:{name:"Indonesia"}}},{id:"420149",title:"Dr.",name:"Rusmana",middleName:"Wijaya Setia",surname:"Wijaya Setia Ningrat",slug:"rusmana-wijaya-setia-ningrat",fullName:"Rusmana Wijaya Setia Ningrat",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Andalas University",country:{name:"Indonesia"}}},{id:"339759",title:"Mr.",name:"Abu",middleName:null,surname:"Macavoray",slug:"abu-macavoray",fullName:"Abu Macavoray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Njala University",country:{name:"Sierra Leone"}}},{id:"339758",title:"Prof.",name:"Benjamin",middleName:null,surname:"Emikpe",slug:"benjamin-emikpe",fullName:"Benjamin Emikpe",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ibadan",country:{name:"Nigeria"}}},{id:"339760",title:"Mr.",name:"Moinina Nelphson",middleName:null,surname:"Kallon",slug:"moinina-nelphson-kallon",fullName:"Moinina Nelphson Kallon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Njala University",country:{name:"Sierra Leone"}}}]}},subseries:{item:{id:"25",type:"subseries",title:"Evolutionary Computation",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. 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