\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"1629",leadTitle:null,fullTitle:"Astrophysics",title:"Astrophysics",subtitle:null,reviewType:"peer-reviewed",abstract:"This book provides readers with a clear progress to theoretical and observational astrophysics. 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\r\n\r\n\tThus, this book welcomes original research and review studies aiming at various aspects of product design with a manufacturing perspective to explore the design strategies, manufacturing limits, and post-manufacturing phases of material enhancement and inspection.
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After her Ph.D. study, she worked as a senior engineer at TEI, a GE-joint venture company specializing in manufacturing aero-engine parts, where she led Additive Manufacturing projects. Later, she joined Eskisehir Osmangazi University as an assistant professor. 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Such definitions generally seek to directly and precisely evidence some physical and structural properties of the object. The Hausdorff dimension [1], recognized as the fractal dimension of a given object, represents a characteristically stationary information of the fractals, that is, it returns an image about the morphology after its formation. In general, this type of parameter becomes very effective in the characterization of several fractal types or different samples, where the process of formation of the same is well-known, such as the case for the deterministic fractals.
\nHowever, the most interesting fractals to be analyzed are those found in nature where the growth processes are not well known. In order to investigate and determine the main phenomena involved in the formation of these fractals, it is vitally important to characterize the growth process of these objects. In this context, we can introduce the pair-pair correlation functions [2].
\nStatistically speaking, the pair-pair correlation functions return probabilistic information related to the dispersion of the constituent parts, taken as fractal singularity elements, to be found by a given characteristic separation. This statistical tool has applications within the analysis of fractal structures and is also commonly used in studies of Molecular Physics, in the analysis and interpretation of simulations of classical molecular dynamics (CMD). Using the taxonomy appropriate to this large area of knowledge, this function is called radial distribution function (RDF) [2]. As structurally CMD simulations require radial information, the most relevant spatial data retrieval takes into account that the dispersion of the particles to be investigated follows a spherical symmetry, hence only analyzing the radial dispersion of the particles.
\nIn fractals with dendritic structures, such as diffusion limited aggregation (DLA) [1], which is a good representation of several physical and biological phenomena in nature, such as crystal growth, formation of polymers, sedimentation processes, among others or deterministic fractals of the group of Julia [3], this type of analysis, through the functions of pair-pair correlation, can elucidate the process of branching for the obtained structures.
\nKnowing how this process develops can helps the scientists to predict the behavior of the Hausdorff dimension of the fractals analyzed, and the fractal morphologies. In the next session, we will present the basic definition of a DLA fractal in a 2D (two dimensional) perspective, which will be the basic archetype for the formal presentation of radial and angular correlation analysis, which will have a basic explanation of the implementation and subsequent analysis of the results obtained.
\nFormally, the diffusion limited aggregation (DLA) was initially studied by Witten and Sander in 1970 [4], and consists of a process of simple aggregate formation that emulates processes of dendritic structures that grow through diffusion, as is the case with of electrodeposition phenomena of solid materials in homogeneous solutions or polymerization process. From a computational modeling point of view, DLA aggregates can be obtained on-lattice and off-lattice, two dimensions (2D) and in three dimensions (3D) both initialized with a single deposited particle, called the seed. Given the diffusive characteristics of the system, all particles are taken as identical and run random walks, until they come into contact with the aggregate when they stop moving and are permanently added to it.
\nThere are several variants of the DLA model, and several ways to obtain a DLA-type aggregate [5]. However, given the statistical properties of the random walk, the simplest way to perform such a simulation is to individually draw each particle and perform several steps of a random walk until one of two events may occur: First, if the particle comes into contact with some particle of the aggregate, the path is terminated and another particle is thrown at a fixed distance from the seed, called the radius of launch
2D DLA off-lattice containing 103 identical particles, showing the respective radii of the aggregates used during the simulation.
The most delicate part of a DLA simulation is the aggregation test. In the on-lattice cases, the test consists of the investigation of the elements of a regular network in the surroundings of the aggregated particles, if any element in the vicinity of the walking particle is occupied, it means that the particle has reached the aggregate and must be glued to it, see Figure 2. In the off-lattice cases, the aggregation is more complicate, since it must be checked at every step if the distance from the center of the walking particle to the center of all the aggregated particles is not less than twice the radius of the particles, if this occurs, the aggregation must be performed. However, double caution must be taken because in these configurations the overlap of particles must be avoided, see Figure 2(b). Several works in the literature have explored algorithms that talk about this problem [6, 7].
\n(a) Aggregation test in a 2D on-lattice DLA, white sites represent empty space, black sites represents spaces occupied by aggregate particles and gray site represents the walking particle. (b) DLA 2D off-lattice aggregation test, black circles are aggregate particles and the gray circle is the walking particle.
As observed by the dendritic growth exposed at Figure 2(a) and (b), the on-lattice simulations have typical different features when compared to the off-lattice simulations, and one special form to quantify this difference is the angular pair-pair correlation function that is discussed in Section 3.
\n\x3c!-- The meaning of sentence “There are some variants …” seems to be unclear. Please clarify.
(a) DLA 2D with 103 particles deposited on-lattice for the case where the seed is deposited in a plane and the particles are thrown on top a plane.
The typical pair-pair correlation function
\x3c!-- As per the instruction all the display equations should be numbered. Hence please check the numbering done for correctness.
where
The radial feature of this distribution does not prevent it from being used in fractals that do not present radial symmetry, as is the case of planar-based DLA, but its analysis must be performed with more cautious. From the computational point of view, it is very rare for the particles to be perfectly separated by the distance
\x3c!-- Please note that color has been mentioned in captions of Figures 4 and 7. Kindly provide alternate references as the figures will be printed in black and white.
When this calculation is performed for different values of
In the case of a typical DLA,
Radial distribution function for the 2D off-lattice DLA containing 104 particles of
(a) DLA 2D off-lattice containing 2 × 103 particles containing one of the branches more developed than the other branches and (b) pair-pair radial distribution function referring to DLA of item (a) of this figure.
The manner in which the dendrites of a DLA-type aggregate or other branched fractal are formed may be extremely relevant in their characterization. One way to characterize such branching is by calculating the angular pair correlation function
Using the primitive ideas of
Mathematically, the correlation function
where
Computationally speaking, it is also very complicated to determine
Schematic diagram of c(
The aggregate particles that have their center inside the circular sector are accounted for in the histogram. After the calculation is performed for all aggregated particles, the sum is divided by the total number of particles added.
\nSimilarly to the case of
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Rescaled
Rescaled
Obviously, the Hausdorff dimension of these anisotropic structures also change, but meanwhile, the calculations of
There are cases in which the constituent species of the fractal/aggregate end up being different from each other, as was discussed in the paper [9]. In this case, it was necessary to create a correlation function for each of the species of particles involved in the aggregation growth process. This example proves the malleability of this type of function in the determination of morphological characteristics of the aggregates.
\nAs observed throughout this chapter, the determination of the main characteristics associated with the morphological structures of two-dimensional fractals, especially those with dendritic properties and radial dispersion, involves the determination of angular correlation functions c(
Please provide the location details for Refs. [1, 2].
Please provide the complete details for Ref. [5].
Hypertension is defined as office or clinic systolic blood pressure (SBP) values >140 mmHg and/or diastolic blood pressure (DBP) values >90 mmHg in adult population [1, 2]. It is one of the major modifiable risk factors for cardiovascular diseases (CVDs) [3]. Hypertension is the main risk factor for cardiovascular diseases, especially for coronary heart disease, heart failure, arrhythmia, stroke, peripheral vascular disease, and also for chronic kidney disease and dementia [4]. Globally, in the year 2017, high systolic blood pressure was the leading risk factor of all-cause deaths, accounting for 10.4 million deaths and 218 million disability-adjusted life-years (DALYs), followed by smoking, high fasting plasma glucose (FPG), high body-mass index (BMI), and short gestation for birth weight. Astonishingly, from 1990 to 2017, high SBP was consistently responsible for the largest number of all-cause deaths, followed by smoking and high FPG respectively [5]. In 2010, 31.1% (1.39 billion people) of the world’s adults had hypertension [6]. The number of adults with hypertension in 2025 was predicted to be a total of 1.56 billion [7].
Currently, hypertension treatment drugs such as adrenoceptor antagonists (propranolol and prazosin), ACE inhibitors (perindopril), angiotensin receptor blockers (irbesartan), mineralocorticoid antagonists (spironolactone), diuretics (thiazides and amiloride), and vasodilators (nitrates, calcium channel blockers, and hydralazine) are being used to control blood pressure in hypertensive patients [8]. Despite, the presence of a plethora of antihypertensive drugs and lifestyle modification strategies for blood pressure control a large number of hypertensive patients remained undiagnosed or untreated or did not control their blood pressure to target level in spite of being treated [6]. The proportion of hypertensive population that got treatment (55.6% in high-income countries (HIC), 29.0% in low and middle-income countries (LMIC)) and that got their blood pressure controlled (28.4% in HIC, 10.3% in LMIC) is astonishingly low [9]. Moreover, up to 40% of patients with hypertension fail to achieve adequate blood pressure control, even when prescribed a combination of drugs from three or more classes [10]. These observations highlight lack of efficacy of the current hypertension prevention and control strategies and also indicate that in some patients at least, additional drivers of hypertension must exist, and new targets need to be identified and targeted for the treatment of hypertension.
Hypertension is associated with chronic low-grade systemic inflammation [11]. It is hypothesized that perturbation in immune system and chronic low-grade systemic inflammation is one of the contributors in development and/or sustaining of hypertension. Accordingly, this book chapter composed existing evidence to show the contribution of perturbation in immune system and chronic low-grade systemic inflammation to the development and/or sustaining of hypertension.
Inflammation is an immune system response to noxious stimuli entered or occurred in a tissue that includes pathogens, damaged cells, toxic compounds, or irradiation; and inflammation acts to remove the noxious agent and to initiate healing process. At tissue level, inflammation is characterized by swelling, redness, heat, pain, and loss of tissue function, which are considered five cardinal signs of inflammation, and these signs result due to local immune, vascular, and inflammatory cells response to infection or injury [12]. In addition to infection and tissue injury, inflammation can be initiated due to disruption of cellular and tissue homeostasis. It has been shown that cells with disrupted homeostasis that undergoes senescence release inflammatory mediators known as the senescence associated secretory phenotypes (SASP). While excessive cell stress such as ER, mitochondrial or osmotic stress that cannot be handled by effector mechanisms within homeostatic regime activates NLRP3 inflammasome [13]. Recently, researchers are mentioning inflammation as a spectrum of a system (organism, tissues, cells) state; homeostatic state, stress response state, and inflammatory state. Indeed, both stress response and inflammation are engaged to eliminate the stressor (i.e., the source of perturbation), to promote adaptations to the stressor, and ultimately to return the system to the homeostatic state [14]. Deviations of regulated variables within a normal range are corrected by the homeostatic circuit (including stress responses) while extreme deviations of regulated variables beyond the homeostatic range trigger the inflammatory response [13]. At the same time, it is important to notice that even though inflammation brings homeostatic state at the end, inflammation and inflammatory mediators are both antagonistic to and dominant over homeostatic signals [14].
Thus, inflammation can be induced by extreme deviations in regulated variables of cellular and tissue homeostasis or by agents that cause disruption of tissue homeostasis, including pathogens, toxins, and xenobiotics [14]. The inflammation process is coordinated by a large range of mediators that form complex regulatory networks. Inflammatory pathway is composed of inflammation inducers, inflammation sensors, inflammation mediators, and inflammatory effectors [15].
Inflammation is a component of the broader and wider immune system. The immune system is composed of a complex network of specialized cells where each type has precise roles. The immune system is an interactive network of lymphoid organs, cells, humoral factors, and cytokines [16]. The immune system has two lines of defense, innate immunity, and adaptive immunity. Innate immunity is nonspecific defense mechanism which is used by the host immediately or within hours of encountering an antigen. It comprises four types of defensive barriers: anatomic (skin and mucous membrane), physiologic (temperature, low pH, and chemical mediators), endocytic and phagocytic, and inflammatory [17]. Innate immunity relies upon a repertoire of germline-encoded receptors, the pattern recognition receptors (PRRs) that recognize the pathogen-associated molecular patterns (PAMPs) to detect microbial structures and the damage-associated molecular patterns (DAMPs) to detect immunological danger (molecules released during the cell lysis and tissue damage) [18]. Innate immunity rapidly recruits immune cells to sites of infection and induces inflammation through the production of cytokines (tumor necrosis factor (TNF), interleukin 1 (IL-1) and interleukin 6 (IL-6)) and chemokines [17]. Moreover, innate immunity is considered as an ingenious doorbell that awakens the adaptive immune response through antigen-presenting cells (APCs) such as dendritic cells (DCs) that present antigens to the lymphocytes (with the optimal T cell receptor (TCR) specificity and affinity) and also costimulatory signals, which guarantee full proliferation and differentiation of the lymphocytes [19]. Adaptive immunity consists of two broad sets of antigen-responsive cells, the B and T lymphocytes. B lymphocytes are the precursors of antibody-producing cells, plasma cells. Antibodies are capable of recognizing three-dimensional structures and thus can interact with and lead to the neutralization of pathogens in extracellular fluid. By contrast, the T cell antigen recognition system recognizes a complex consisting of an antigen-derived peptide bound into a specialized groove in class I and class II major histocompatibility complex (MHC) molecules of APCs [20]. CD8+ T cells can interact with peptides (9–11 amino acids in length) on almost any cell expressing MHC class I while the TCRs of CD4+ T cells engage peptides bearing MHC class II. The activated T cells can play direct roles in elimination of pathogens by killing infected target cells, they can function by providing cognate (involving direct cellular contact) or cytokine signals to enhance both B- and T-cell responses, as well as causing activation of mononuclear phagocytes, and also T cells regulate immune responses, limiting tissue damage incurred by means of autoreactive or overly inflammatory immune responses [21]. In adaptive immunity, long-lived memory cells (memory lymphocytes) ensure that a second encounter with the same invader is dealt with swiftly and effectively because of the greater number (for the given antigen), extended lifespan, more rapid response rate, superior proliferation capacity, and wider access to tissues of the memory lymphocytes [19].
Inflammation plays a vital role in preserving physiological homeostasis of an organism, in protection against invading agents such as bacteria and virus, and in healing processes of damaged tissue. On the other hand exaggerated inflammation or chronic inflammation can cause tissue damage, and contributes for the development and/or persistence of many diseases [22]. Acute inflammatory response can be initiated during times of infection or in response to physical, chemical, or metabolic noxious stimuli through interaction between pattern recognition receptors expressed on innate immune cells and PAMPs or DAMPs. On the other hand, chronic low-grade systemic inflammation is typically triggered in the absence of an acute infectious insult [23].
Chronic low grade systemic inflammation is a low-grade, systemic, unresolved, and smoldering chronic inflammation clearly indicated by a 2- to 4-fold increase in serum levels of inflammatory mediators, including interleukin-6 (IL-6) and acute phase proteins, for example, C-reactive protein (CRP); even though there is no numerical cut off values for elevated inflammatory mediators to define chronic low grade systemic inflammation at the present time [24]. In chronic low grade systemic inflammation, besides CRP and IL-6, a large number of cellular (total leukocytes, granulocytes, and activated monocytes) and pro- and anti-inflammatory mediators including IL-1, IL-8, IL-13, IL-18, interferon-α and interferon-β, tumor necrosis factor, CC chemokine ligands, adhesion molecules, and acute-phase reactants (serum amyloid A, and fibrinogen) are involved or are produced as a result of the inflammatory processes. Chronic low grade systemic inflammation is associated with many chronic disease conditions including CVDs, neurodegenertion and Alzheimer’s disease, insulin resistance and type 2 diabetes mellitus, tumorigenesis and cancer, osteoporosis, anemia, chronic kidney disease, depression, sarcopenia, and disability [25].
Whereas hypertension has predominantly been ascribed to perturbations of the vasculature, kidney, and central nervous system, researches have shown that the immune system also contributes to this disease. Inflammatory cells that accumulate in the kidneys and vasculature of humans and experimental animal models with hypertension likely contribute not only for pathogenesis of hypertension but also contribute to end-organ damage [26].
An association between hypertension and inflammation has been clearly demonstrated while it is not clear whether inflammation is predominantly a cause or an effect of hypertension [11]. Many studies indicated that an inflammatory marker CRP level increases as blood pressure level increases. A prospective follow up study done on 15, 215 women found that, in cross-sectional analyses of baseline data of the study, increasing categories of blood pressure were significant predictors of CRP levels; meaning linear increase in levels of CRP was seen as levels of systolic blood pressure or diastolic blood pressure increases [27]. Another case-control study done among 904 participants, 39–50 years old, found a continuous, independent association between serum CRP and elevated blood pressure. The study also reported that, after adjustment for sex, obesity, race, serum insulin level and family history of coronary heart disease, odds ratios for hypertension increased progressively across CRP quintiles; participants in the highest CRP quintile were 2.35 times more likely to have hypertension than those in the lowest quintile [28]. Similarly, a case-control study done on 1529 subjects (767 hypertensive and 762 non-hypertensive) aged from 30 to 84 years, reported that the means for BP and CRP in cases (hypertensive subjects) were significantly higher than that in controls (non-hypertensive subjects) [29]. A study carried out on 335 non-hypertensive study participants, with mean arterial blood pressure of 135/85 mmHg and age of 65 years at base line, indicated that the 2-year risk for new-onset hypertension was 18% greater for 1 mg/l increment of CRP after adjustment for low-density lipoprotein cholesterol and BMI [30]. A prospective cohort study done on 20,525 female USA health professionals aged 45 years or above found that the adjusted relative risk (RR) of developing hypertension is 1.5 for the group with the highest level of CRP at base line compared with the group of the lowest CRP at the base line. From their cohort study, the study group concluded that CRP levels are associated with future development of hypertension [31].
Similar to association trend observed between CRP and blood pressure, higher level of other pro-inflammatory cytokines were reported among hypertensive population or individuals with higher blood pressure (BP) levels compared with non-hypertensive population or individuals with lower BP levels. A study done on 79 hypertensive and 117 non-hypertensive study subjects showed that plasma Il-6 and TNF-α were significantly higher (two to four times higher) in hypertensive subjects compared to non-hypertensive subjects [32]. Similarly, another study that assessed association of blood pressure level with plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and interleukin-6 (IL-6) among 508 apparently healthy men, found increasing levels of SBP, pulse pressure (PP), and mean arterial pressure (MAP) were significantly associated with increased levels of sICAM-1 while all blood pressure parameters (SBP, DBP, PP, MAP) were significantly associated with increasing levels of IL-6 [33]. Two independent studies that compared the serum and the peripheral blood mononuclear cells (PBMCs) IL-1β levels among hypertensive and non-hypertensive groups found significantly higher level of IL-1β among hypertensive groups [34, 35].
Experimental studies on animals also confirmed association between hypertension and inflammation. An experimental study that compared blood pressure levels among angiotensin II (Ang II) infused mice (wild type mice versus IL-6 deficient mice (IL6−/−) found that in wild-type mice systolic blood pressure began to increase by day 3, increased significantly by day 7, reached a peak by day 10, and continuously maintained high blood pressure through the end of 2-week Ang II infusion while genetic deletion of IL-6 in mice led to a significant reduction of Ang II-induced hypertension [36]. Another experimental study showed that RNA interference knockdown of IL-6 in Sprague-Dawley rats abolished the cold-induced upregulation of IL-6 in kidney and aorta, and also significantly attenuated cold-induced elevation of systolic blood pressure [37].
An experimental study that compared effect of Ang II to infusion into wild types (WT) mice and TNF-α knockout (KO) (TNF-α−/−) mice found that Ang II infusion for 14 days significantly increased mean arterial pressure in WT mice from (115 ± 1 to 151 ± 3 mmHg) but not in TNF-α−/− mice (113±2 to 123±3 mm Hg). The study also showed that, when TNF-α−/− mice are given replacement therapy with human recombinant TNF-α, Ang II administration caused an increase in mean arterial pressure (109 ± 1 to 153 ± 3 mm Hg) [38]. Another experimental study done on mice, which compared blood pressure level among angiotensin II infused WT mice and type 1 interleukin-1 receptor (IL-1R1)-deficient (KO) mice showed that during chronic Ang II infusion, the IL-1R1 KO animals were partially protected from hypertension compared to the WT controls (165±6 versus 180±3 mmHg). The study also reported administering an IL-1R1 antagonist (anakinra) or vehicle to WT mice for 3 days prior to and during chronic Ang II infusion resulted in IL-1R1 blockade with anakinra significantly attenuated the level of blood pressure elevation during chronic Ang II infusion (154 ± 4 versus 167 ± 3 mmHg). Both isoforms of IL-1 (IL-1α and IL-1β) bind and signal via the IL-1R1 [39].
An experimental study that investigated effect of a proinflammatory cytokine interleukin 17 (IL17) reported that initial hypertensive response was similar for wild type mice (C57BL/6J mice) and interleukin 17 deficient mice (IL17−/− mice) however hypertension was not sustained in IL17−/− mice, reaching levels 30 mmHg lower than in wild type mice by 4 weeks of angiotensin II infusion. Moreover, blood vessels from IL17−/− mice displayed preserved vascular function, decreased superoxide production, and reduced aortic T cell infiltration in response to angiotensin II infusion which is indicative for importance of IL17 for the maintenance of angiotensin II-induced hypertension and vascular dysfunction [40].
In addition to above mentioned human and animal studies that showed association between inflammatory cytokines and hypertension, many studies implicated that both innate and adaptive immunity cells play roles in hypertension pathophysiology.
Variability, diversity, and joining (V(D)J) recombination is the specialized DNA rearrangement used by cells of the immune system to assemble immunoglobulin and T-cell receptor genes from the preexisting gene segments. The RAG1 and RAG2 proteins are the only lymphoid-specific factors needed for V(D)J recombination that generate diverse B-lymphocytes antibodies and T-cell receptors [41]. An experimental study on mice showed that in mice with genetic deletion of the recombinase-activating gene (RAG-1−/−) mice, mice that lack both T and B lymphocytes, hypertension caused by chronic low-dose angiotensin II infusion was markedly blunted. Similar to response for angiotensin II infusion, in the experimental study, the increase in blood pressure was also blunted in RAG-1−/− mice in desoxycorticosterone acetate (DOCA) – salt hypertension model, indicating that lymphocytes likely play a role in different types of hypertension. Besides, in the RAG-1−/− mice study, adoptive transfer of B cells into RAG-1−/− mice had little effect on the increase in blood pressure while adoptive transfer of T cells restored the hypertension response to angiotensin II infusion. This study indicated that the T lymphocyte plays a critical role in the development of hypertension [42].
A study done on mice showed that infusion of angiotensin II for 14 days into wild type (WT), CD4−/−, and CD8−/− mice resulted in blunted blood pressure increase in CD8−/− mice while WT and CD4−/− mice exhibited increased blood pressure in response to angiotensin II. The study also reported that an increase in blood pressure in response to deoxycorticosterone acetate (DOCA)-salt challenge was significantly reduced in CD8−/− mice compared to either CD4−/− or WT mice, similar to angiotensin II-induced hypertension response [43]. It is known that mice lacking CD4 (CD4−/− mice) also lack regulatory T cells (Tregs) which may predispose to aggravated hypertension in CD4−/− mice in the above mentioned experimental study [43].
Osteopetrotic (Op/Op) mice have no colony-stimulating factor 1 gene and thus they lack colony-stimulating factor l (CSF-1), and are functionally deficient in macrophages [44]. In an experimental study done on adult Op/Op, heterozygous (Op/+), and wild type (+/+) mice, infusion of Ang II for 14-days resulted in significantly increased blood pressure in wild type (+/+) and heterozygous (Op/+) mice while blood pressure in Op/Op remained unaffected from base line level [45]. Similarly, in a study where Op/Op, heterozygous (Op/+), and wild type (+/+) mice given deoxycorticosterone acetate (DOCA)-salt for 14 days, systolic blood pressure (mmHg) was significantly increased (146 +/− 2 and 138 +/− 1; P < 0.001 vs. basal 115 +/− 3 and 115 +/− 3) in wild-type (+/+) and heterozygous (Op/+) mice respectively, but not in Op/Op mice (130 +/− 1 vs. basal 125 +/− 3) [46].
In an experimental study which selectively ablated lysozyme M-positive (LysM+) myelomonocytic cells by low-dose diphtheria toxin in mice with inducible expression of the diphtheria toxin receptor (LysM iDTR), thus the experimental group of mice have reduced number of monocytes in the circulation of the mice without affecting number neutrophils, showed that attenuated Ang II-induced blood pressure increase among experimental group compared to control group [47].
Activation of T cells requires two signals; the first involves interaction of the T cell receptor with an antigenic peptide presented in the context of major histocompatibility complex on antigen-presenting cells (APCs) while the second, referred to as costimulation, involves the simultaneous interaction of receptors in proximity to the TCR with ligands on the APC. Among several potential costimulatory interactions, the binding of T cell CD28 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (CD152) with B7 ligands CD80 and CD86 on APCs is important, particularly for activation of naïve T cells [48]. A study done on mice showed that blockade of B7-dependent costimulation of T-cells with CTLA4-Igl reduced both angiotensin II- and DOCA-salt induced hypertension. Moreover, in mice lacking B7 ligands (B7−/− mice), due to genetic deletion of both CD80 and CD86, angiotensin II caused minimal blood pressure elevation and vascular inflammation, and these effects were restored by transplant with wild-type bone marrow. This study indicated that stimulation of T-cells by dendritic cells is important in both angiotensin II- and DOCA-salt induced hypertension [49].
A study was done on mice that are genetically deficient of B cells, B-cell–activating factor receptor-deficient (BAFF-R−/−) mice, showed that while Ang II infusion caused a rapid rise in SBP from 117 ± 3 mmHg at baseline to a maximum level of 165 ± 5 mmHg by day 21 in wild type mice, the pressor response to Ang II was attenuated in BAFF-R−/− mice with SBP reaching a maximum of only 149 ± 4 mm Hg at day 21 and remaining at this level until day 28 from the base BP level 112 ± 3 mm Hg. Moreover, the study showed that the introduction of B cells into BAFF-R−/− mice were sufficient to fully recapitulate the pressor response to Ang II to levels observed in wild-type mice. This study demonstrated that B cells are crucial for the development of Ang II-induced hypertension [50]. Mutations in the BAFF-R are associated with B-cell lymphopenia and antibody deficiency.
In an experimental study done on Ang II-induced hypertension mice model, mice injected with CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) and infused with hypertension doses of Ang II (400 ng/kg/min) for 2 weeks showed significantly lower increment in blood pressure compared with mice that infused only hypertension doses of Ang II [51]. Similarly, another study on mice reported that mice injected CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) three times, at two-week intervals and then infused with Ang II for 14 days showed blunted increase of SBP compared with control group (group that did not receive regulatory T cells) [52]. In another experimental study that compared blood pressure change among mice received aldosterone infusion and 1% saline in drinking water, mice that infused with aldosterone and received Treg cells adoptive transfer did not show significant increase in both systolic and diastolic blood pressure when compared with control group mice (control mice were similarly injected intravenously with vehicle and received tap drinking water); while mice group that was infused with aldosterone and given 1% saline in drinking water without receiving Treg cells showed significant increase in both systolic and diastolic blood pressure compared to control group [53]. On contrary to the above mentioned study results one experimental study on mice reported that mice that received Treg cells and infused with Ang II showed similar incitement in blood pressure with group of mice that infused Ang II without receiving transfer of Treg cells [54]. The different results of the latter study may be due to differences in experiment procedures as all former studies performed Treg cells transfer few weeks before infusion of Ang II or aldosterone while the latter study performed Treg cells transfer and Ang II infusion simultaneously.
Thus, the existing body of knowledge clearly confirmed existence of association between immune system activation and hypertension while ascertaining the cause effect relationship between inflammation and hypertension needs further study.
An individual’s blood pressure is largely determined by the functions of three key organs, namely the heart which pumps blood through the circulatory system, the blood vessels which regulate blood flow through the organs and the whole body, and the kidneys which regulate sodium and water excretion and hence blood volume. The maintenance of physiological blood pressure levels involves coordinated control and regulation from neurohormonal system which includes the renin-angiotensin-aldosterone system (RAAS), the natriuretic peptides and the endothelium, the sympathetic nervous system (SNS) and the immune system on functions of the heart, blood vessels and the kidneys. Perturbation in function of organs or systems that are involved in BP control can directly or indirectly lead to increase in blood pressure that ultimately ends up in the development of hypertension, and over time results in target organ damage such as, left ventricular hypertrophy and chronic kidney disease (CKD) and CVD outcomes [55].
Existing observational and experimental studies highlight that in some hypertensive patients at least, additional drivers of hypertension must exist than the already known mechanisms involved in pathophysiology of hypertension, and new targets must be defined [10]. Inflammation and immune system perturbation are likely contributors in the development and sustaining of hypertension. The current overarching hypothesis about inflammation and immune system involvement in pathophysiology of hypertension is that immune cells accumulation in blood vessels (in particular, in the perivascular fat), kidneys, heart, and brain promote a chronic inflammatory response that disrupts the blood pressure-regulating functions of these organs, leading to hypertension [56]. Accordingly, inflammation and immune system activation cause derangement in kidneys, arteries, brain, and heart functions that consequently promote hypertension and end-organ damage [57].
In support of the above mentioned hypothesis, current studies indicated that known stimuli that raise blood pressure (such as high-salt diet, Ang II, and DOCA-salt) directly and indirectly activate immune system cells. Elevated blood pressure can stress tissue cells to the level that DAMPs released by tissues. Moreover, hypertensive stimuli can directly activate immune cells and also cause formation of neoantigens in the tissues. As a result of released DAMPs, neoantigens, and direct immune cells activation by hypertension stimuli, activated immune cells are formed, target organs infiltrated by activated immune cells, and diverse inflammatory cytokines are released by the activated immune cells. Eventually, the affected target organs, mainly the kidney, blood vessels, and sympathetic nervous system function are perturbed and this leads to further elevated blood pressure level and finally to hypertension. Immune cells such as monocytes, macrophages, and dendritic cells (DCs) release pro-hypertensive cytokines that promote the BP elevation via actions in the vasculature (augmenting vascular dysfunction), kidney (increasing sodium retention), and stimulating sympathetic nervous system outflow [58].
Many studies implicated that in the kidney, inflammatory cells and their products contribute to blood pressure elevation at least in part by increasing renal sodium transport [59].
Genetic deletion of IL-6 in mice results in blunted hypertension in response to angiotensin II infusion [60]. Treating cortical collecting duct cells culture with IL-6 (100 ng/ml) for 12 h caused increased expression and activity of the epithelial sodium channel (ENaC) [61]. Mutations in ENaC that increase sodium reabsorption lead to the development of high blood pressure in Liddle’s syndrome (a rare inherited form of hypertension) while mutations that inactivate ENaC have also been identified in humans, and these mutations lead to low blood pressure [62]. Taken together, these studies suggest that IL-6 enhances renal tubule sodium reabsorption and elevates BP at least in part through up regulation of renal tubule ENaC.
IL-1 is a pro-inflammatory cytokine that plays a central role in both acute and chronic inflammation, acting as a primary inducer of the innate immune response. Studies indicated that type 1 IL-1 receptor (IL-1R1) stimulation by IL-1 potentiates blood pressure elevation by suppressing nitric oxide (NO)-dependent sodium excretion in the kidney. Nitric oxide is a potent driver of sodium excretion in the kidney that acts via cyclic guanosine monophosphate (cGMP) and phosphodiesterase two to limit Na-K-2Cl cotransporter (NKCC2) activity in the medullary thick ascending limb. Thus, by relieving NO inhibitory effect on NKCC2, IL-1 enhances reabsorption of electrolytes by medullary thick ascending limb and enhances retention of sodium and water by kidney [39].
Interferon gamma (IFN-γ) is a proinflammatory cytokine produced by innate and adaptive immune cells, and T cell production of IFN-γ is increased in Ang II-induced hypertension and mice deficient in IFN-γ have a blunted blood pressure response to Ang II infusion. Experimental studies indicate that IFN-γ positively regulates sodium hydrogen exchanger 3 (NHE3) in the proximal tubule, NKCC2 in medullary thick ascending limb, and NCC in the distal tubule. Whether IFN-γ directly modulates these sodium transporters or acts through downstream mediators is unknown [62].
Interleukin 17A (IL-17A) is a pro-inflammatory cytokine produced predominantly by CD4+ T helper 17 (Th17) cells as well as gamma delta T cells. An experimental study that investigated effect of a proinflammatory cytokine interleukin 17 (IL17) reported that initial hypertensive response was similar for wild type mice (C57BL/6J mice) and interleukin 17 deficient mice (IL17−/− mice) however hypertension was not sustained in IL17−/− mice in Ang II hypertension model [40]. Mice model experimental studies and cell culture model studies showed that interleukin 17A up regulates NHE3 (in proximal segment), NCC and ENaC (in distal segment) of renal tubules. Moreover, studies implicated that interleukin 17A regulates renal sodium transporters through a serum and glucocorticoid regulated kinase 1 (SGK1) dependent pathway [63]. Serum and glucocorticoid regulated kinase1 is an important mediator of salt and water retention in the kidney through inhibition of neural precursor cell expressed developmentally down-regulated 4-2 (Nedd4-2) mediated ubiquitination and degradation of NHE3, NCC, and ENaC in the renal tubule, thereby enhancing the expression of these transporters on the cell surface [64].
Besides its effect on electrolyte and water homeostasis regulation function of kidney, sustained inflammation results in renal fibrosis, oxidative stress, glomerular injury, and chronic kidney disease [59].
Blood vessels are other organs that are affected by activated immune system and chronic low grade inflammation associated with hypertension. Elevated blood pressure has an impact on the vasculature as a consequence of both the mechanical effects of blood pressure and shear stress [65]. Inflammation can impair blood vessels in two ways. Inflammation can cause functional arterial stiffening by impairing the functional relaxation capability of arteries. The other mechanism is structural remodeling of arteries due to hypertension-associated inflammation [66]. Likewise, many experimental studies confirmed involvement of immune cells and inflammatory cytokines in vascular dysfunction associated with experimental hypertension.
An experimental study done on mice showed that Ang II infusion in mice increased immune cell content (T cells, macrophages, and dendritic cells) in perivascular adipose tissue and adventitia [67].
Endothelial cell culture study showed that inflammatory marker, C-reactive protein (CRP), caused a marked down regulation of endothelial nitric oxide synthase (eNOS) mRNA and protein expression [68]. Similarly, TNF-α mediated inhibition of eNOS expression was observed in endothelial cell culture [69]. Acute treatment of endothelial cells with IL-17 caused a significant increase in phosphorylation of the inhibitory eNOS residue threonine 495 (eNOS Thr495) [70]. All these studies indicate that inflammation decreases bioavailability of endothelial NO and thus impairs vascular smooth muscle relaxation and subsequent vasodilatations.
Moreover, involvement of immune cells and inflammatory cytokines in hypertensive vascular remodeling is implicated by many studies. Reduced vascular remodeling showed in Ang II or DOCA- salt induced hypertension in osteopetrosis (Op/Op) mice [10]. In RAG1−/− mice (mice deficient in T and B lymphocytes) reduced aortic and small artery remodeling observed in response to Ang II-induced hypertension [41]. Similarly, interleukin 17A deficient (IL-17a−/−) mice are protected against aortic collagen deposition and aortic stiffening in response to chronic angiotensin II infusion [71]. These studies implicated that immune cells and inflammatory cytokines play roles in vascular fibrosis, remodeling of small and large vessels, and vascular rarefaction in hypertension. Nonetheless, this remains to be further investigated.
Other important organ both in development of hypertension and as an end-organ target of hypertension is the brain. Regulation of short-term blood pressure level by sympathetic nervous system (SNS) is well established. SNS stimulation is associated with constriction of blood vessels, increased cardiac output, and augmented sodium and fluid retention by the kidneys [72]. Moreover, SNS serves as an integrative interface between the brain and the immune system.
Mounting evidence implicate that many forms of essential hypertension are initiated and maintained by an elevated sympathetic tone [73]. The elevated sympathetic activity can be initiated by several factors including humoral factors such as angiotensin II and by environmental factors such as stress and high salt intake. In view of sympathetic nervous system substantial innervation to both primary (thymus, bone marrow) and secondary (spleen, lymph nodes, Peyer’s patches) lymphoid tissues, and the central nervous system (CNS) powerful influences on the immune system and vice versa, it is reasonable to suppose that CNS enhance immune responses that lead to hypertension [74]. Pro-inflammatory cytokines (such as TNF-α, IL-1β) produced in the periphery can signal to the brain, passing through the BBB at points of increased permeability in the circumventricular organs (CVOs) and/or through disrupted blood brain barrier (BBB), and results in increased sympathetic outflow [75].
Observations such as increased splenic sympathetic nerve discharge (SND) and consequent increase in splenic cytokine gene expression (IL-1β, IL-6, IL-2, and IL-16) due to central Ang II administration (the effect which was abrogated by splenic sympathetic denervation), and others led to the hypothesis that central stimuli such as angiotensin II cause modest elevations of blood pressure, which leads to activation of immune system. Subsequently, the activated immune system leads to severe hypertension [76]. This hypothesis proposed a mechanism that occurs in a two-phase feed forward fashion. The initial phase brings a modest elevation in blood pressure (i.e. pre-hypertension), giving rise to an inflammatory response, possibly by generating “neoantigens” that activate innate and adaptive immune system. In the second phase, the activated immune system generates cytokines and other inflammatory mediators which work in concert with the direct effects of hypertensive stimuli (such as angiotensin II, catecholamines, and salt) to cause vascular and renal dysfunction, promote vasoconstriction, vascular remodeling, a shift in the pressure-natriuresis curve and sodium retention, and ultimately causes sustained hypertension [74].
Hypertension is a widely prevalent public health problem of world adult population. It is a major risk factor of cardiovascular diseases, chronic kidney disease, and dementia. Despite the availability of a plethora of hypertensive drugs, up to 40% of patients with hypertension fail to achieve adequate blood pressure control, even when prescribed a combination of drugs from three or more classes. This indicates lack of efficacy of existing hypertension treatment strategies and existence of additional drivers of hypertension that must be identified and may be targeted.
One of the proposed pathophysiologic mechanisms that contribute for elevated BP and target organ damage among hypertensive patients is activation of the immune system and chronic low grade systemic inflammation.
In kidneys, inflammatory cells and their products contribute to blood pressure elevation by increasing renal sodium retention and by causing renal fibrosis, oxidative stress, and glomerular injury. IL-1, IL-6, IFN-γ, and IL-17 are among pro-inflammatory cytokines that enhance sodium retention by renal tubules.
Activated immune cells and pro-inflammatory cytokines may contribute to functional arterial stiffening and structural remodeling of arteries that consequently cause elevated blood pressure in hypertension. C-reactive protein, TNF-α, and IL-17 may hamper synthesis of or inhibit nitric oxide (NO) synthase. Inflammatory cells that infiltrate blood vessels such as macrophages and lymphocytes and their pro-inflammatory products may also contribute for vascular remodeling.
Perturbed immune system and chronic low grade systemic inflammation also enhance SNS activity which in turn contributes to elevated blood pressure by its effect on blood vessels tone (vasoconstriction), on the kidneys (sodium and water retention, RAAS activation) and on immune system (activation of immune system and enhanced production pro-inflammatory cytokines).
Thus, unraveling the detail pathophysiological mechanisms by which activated immune system and inflammation contribute to hypertension paves a way to identify target, and to design and develop therapeutic intervention for hypertension.
Even though currently there is no anti-inflammatory drug to treat hypertension, anti-inflammatory agents that target specific inflammatory pathway (without compromising general immune system of an individual) are possible future hypertension treatment drugs.
Author does not have any conflict of interest whatsoever with regard to content or opinions expressed above.
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",metaTitle:"Waiver Policy",metaDescription:"We feel that financial barriers should never prevent researchers from publishing their research. With the need to make scientific research more publically available and support the benefits of Open Access, more institutions and funders have dedicated funds to assist their faculty members and researchers cover the APCs associated with publishing in Open Access. Below we have outlined several options available to secure financing for your Open Access publication.",metaKeywords:null,canonicalURL:"/page/waiver-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"At IntechOpen, the majority of OAPFs are paid by an Author’s institution or funding agency - Institutions (73%) vs. Authors (23%).
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Exoplanet characteristics and their comparison to Solar System planets are provided as well as general detection methods and planned probes to gather additional data.",book:{id:"10210",slug:"solar-system-planets-and-exoplanets",title:"Solar System Planets and Exoplanets",fullTitle:"Solar System Planets and Exoplanets"},signatures:"Joseph Bevelacqua",authors:[{id:"115462",title:"Dr.",name:"Joseph",middleName:"John",surname:"Bevelacqua",slug:"joseph-bevelacqua",fullName:"Joseph Bevelacqua"}]},{id:"65725",title:"On the Deviation of the Lunar Center of Mass to the East: Two Possible Mechanisms Based on Evolution of the Orbit and Rounding Off the Shape of the Moon",slug:"on-the-deviation-of-the-lunar-center-of-mass-to-the-east-two-possible-mechanisms-based-on-evolution-",totalDownloads:984,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"It is known that the Moon’s center of mass (COM) does not coincide with the geometric center of figure (COF) and the line “COF/COM” is not directed to the center of the Earth, but deviates from it to the South-East. Here, we discuss two mechanisms to explain the deviation of the lunar COM to the East from the mean direction to Earth. The first mechanism considers the secular evolution of the Moon’s orbit, using the effect of the preferred orientation of the satellite with synchronous rotation to the second (empty) orbital focus. It is established that only the scenario with an increase in the orbital eccentricity e leads to the required displacement of the lunar COM to the East. It is important that high-precision calculations confirm an increase e in our era. In order to fully explain the shift of the lunar COM to the East, a second mechanism was developed that takes into account the influence of tidal changes in the shape of the Moon at its gradual removal from the Earth. The second mechanism predicts that the elongation of the lunar figure in the early era was significant. As a result, it was found that the Moon could have been formed in the annular zone at a distance of 3–4 radii of the modern Earth.",book:{id:"8444",slug:"lunar-science",title:"Lunar Science",fullTitle:"Lunar Science"},signatures:"Boris P. Kondratyev",authors:[{id:"277909",title:"Prof.",name:"Boris",middleName:"Petrovich",surname:"Kondratyev",slug:"boris-kondratyev",fullName:"Boris Kondratyev"}]},{id:"68357",title:"Solar System Exploration Augmented by In Situ Resource Utilization: System Analyses, Vehicles, and Moon Bases for Saturn Exploration",slug:"solar-system-exploration-augmented-by-in-situ-resource-utilization-system-analyses-vehicles-and-moon",totalDownloads:824,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Human and robotic missions to Saturn are presented and analyzed with a range of propulsion options. Historical studies of space exploration, planetary spacecraft and astronomy, in situ resource utilization (ISRU), and industrialization all point to the vastness of natural resources in the solar system. Advanced propulsion is benefitted from these resources in many ways. While advanced propulsion systems were proposed in these historical studies, further investigation of nuclear options using high-power nuclear electric and nuclear pulse propulsion as well as advanced chemical propulsion can significantly enhance these scenarios. Updated analyses based on these historical visions are presented. At Saturn, nuclear pulse propulsion with alternate propellant feed systems and Saturn moon exploration with chemical propulsion and nuclear electric propulsion options are discussed. Issues with using in situ resource utilization on Saturn’s moons are discussed. At Saturn, the best locations for exploration and the use of the moons as central locations for Saturn moon exploration are assessed. 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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. 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He is also Member of the Laboratory of genetic, animal and feed resource and member of Animal science Department of INAT. He graduated from Higher School of Agriculture of Mateur, University of Carthage, in 2002 and completed his masters in 2006. Dr. M’HAMDI completed his PhD thesis in Genetic welfare indicators of dairy cattle at Higher Institute of Agronomy of Chott-Meriem, University of Sousse, in 2011. 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Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"95",type:"subseries",title:"Urban Planning and Environmental Management",keywords:"Circular economy, Contingency planning and response to disasters, Ecosystem services, Integrated urban water management, Nature-based solutions, Sustainable urban development, Urban green spaces",scope:"