\r\n\tFurthermore, during the preparation of high-quality dairy products, several physical, chemical, enzymatic, and microbial transformations take place. We will consciously focus on this interaction of different constituents of milk under different processing conditions for the development of the products.
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The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",doi:"10.5772/intechopen.103760",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",body:'Even for students just beginning to study biochemistry and physiology, it is immediately apparent that amino acids (AAs) are among the most important molecules in nature. Their functions are broad and varied. Indeed, protein synthesis relies on the well-known polymerization of AAs to form a peptide bond. This property is the most famous aspect of AAs. However, many AAs have specific individual functions, such as neurotransmission [1], cellular energy metabolism [2], and detoxification [3, 4]. Accumulating evidence in recent years has demonstrated that AAs also regulate both the expression of genes and the protein phosphorylation cascade. Moreover, hormones and different low-molecular-weight biologically important chemical compounds can be synthesized from AAs [5]. AAs can be divided into essential and nonessential categories. If the body cannot synthesize the carbon skeleton of an amino acid, then it is considered nutritionally essential. Indeed, the diet must contain such AAs. The dietary essentiality of other AAs (e.g., arginine, glycine, proline, and taurine) is determined by the developmental stage and species [6]. In contrast, if AAs can be synthesized de novo in a species-dependent manner, they are considered nonessential. Accumulating evidence has led to the concept of functional AAs (FAAs), which are defined as AAs that regulate key metabolic pathways to improve the health, survival, growth, development, lactation, and reproduction of organisms [7]. Since the late 1970s, researchers have generally agreed that amino acids can also function as inhibitory or excitatory neurotransmitters [8]. It should be noted that in neurochemistry, the term “neurotransmitter” is usually used synonymously with “neuromediator,” another term for a chemical participant in connections between neurons and neuroglia cells. Because these terms are exchangeable, they will both be used in the text. Based on their effects on vertebrate nerve cells, γ-aminobutyric acid (GABA), glycine, and taurine fall into the class of inhibitory amino acids, whereas glutamate and aspartate fall into the class of excitatory compounds [9]. Indeed, GABA is considered the main inhibitory neurotransmitter in the central nervous system (CNS) [10], but it is not truly a member of the AA family. Although taurine also plays a role in inhibitory neuromediation [11] and serves as an osmoeffector to regulate volume in astrocytes [12], this compound is considered a derivative of cysteine, and, similar to GABA, not a true amino acid. Thus, the remaining excitatory/inhibitory amino acid neurotransmitters are glutamate, aspartate, and glycine. The first and third are the most prominent members of the AA family. The processes that regulate glutamate and glycine in the CNS are (i) transportation, (ii) biochemical transformations in metabolic pathways, and (iii) interactions with membrane receptors. In the current chapter, the crosstalk between the processes mentioned above for both glutamate and glycine is presented because the final state of neurons seems to be a result of the balance between these excitatory and inhibitory influences.
Glutamate and glycine are nonessential amino acids; their levels differ depending on the location. The extracellular glutamate concentration around quiescent neurons is less than 1 μM, while its concentration in the cytoplasm is much higher, at approximately 2 mM [13]. The brain sequesters glycine in concentrations of 600 μM [14], with a basal concentration in the cerebrospinal fluid (CSF) of ~6 μM [15], compared to a plasma concentration of ~250 μM [16]. Because no extracellular enzymes degrade glutamate and glycine, maintaining these low extracellular concentrations requires cellular uptake of both compounds. Thus, the activity of the carriers directly regulates receptor response to neuron activation. Indeed, glutamate and glycine serve as neuromediators in the extracellular fluid because the binding site of AA receptors is exposed to the outer surface of cells. Consequently, the release of AA into the extracellular fluid controls receptor activation and active states are controlled by the removal of AAs from the extracellular fluid [17]. This uptake is catalyzed by a family of transporter proteins located on the cell surface of both astrocytes and neurons [17]. A high-affinity glutamatergic uptake system was observed in the mammalian brain in the 1970s. Subsequently, excitatory amino acid transporters (EAATs) were experimentally identified. They transport glutamate and aspartate across the plasma membrane. Notably, EAATs are part of the well-known solute carrier 1 (SLC1) family of transmembrane amino acid transporters [18]. Thus, released glutamate molecules can be removed from the synaptic cleft by the brain transporters; this process will initiate the glutamate-glutamine cycle, eventually restoring the pool of the neuromediator in synaptic vesicles [19]. Five EAAT isoforms, human EAAT1-5, have been identified; they correspond to GLAST1/GLT-1/EAAC1/EAAT4/EAAT5 in rodents, respectively [20]. In addition, the EAAT4 and EAAT5 subtypes were identified, with EAAT5 predominantly expressed in the retina. Notably, the transport cycle times of EAATs are relatively slow and their high affinity for glutamate makes it possible to sequester low glutamate concentrations from the extracellular space, preventing excitotoxicity. The slow transportation rate may in part be overcome by rapid surface diffusion and transporter tracking of EAATs upon glutamate stimulation [21]. The SLC1 family also contains two neutral amino acid transporters, alanine serine cysteine transporters 1 and 2 (ASCT1 and 2), which share high sequence homology with the EAATs [22]. EAAT1 and EAAT2 are glutamate transporters that are mostly expressed in astrocytes. These two glutamate transporters are responsible for most of the glutamate clearance in the brain. EAAT2 is widely expressed in the cerebral cortex and the hippocampus [13]. Moreover, GLT-1/EAAT2 accounts for approximately 90% of the total glutamate uptake in the brain, and thus, it is considered the most important glutamate transporter subtype in the CNS. This transporter is predominantly but not exclusively expressed in astrocytes [22]. Glutamate transporters couple glutamate uptake to the transport of inorganic ions. It is now generally accepted that 3 Na+ ions and 1 H+ ion are cotransported and 1 K+ ion is counter-transported with the uptake of each glutamate molecule. Based on this stoichiometry, glutamate transporters were calculated to concentrate glutamate up to 5 × 106-fold inside cells under physiological conditions. This glutamate transport is electrogenic [23].
The extracellular levels of glycine in inhibitory and excitatory synapses are controlled by glycine transporters (GlyTs). Both subtypes, GlyT1 and GlyT2, belong to the sodium-dependent solute carrier 6 (SLC6) family of transporters, but they have different regional and cellular expression patterns in the CNS, different stoichiometries (that is, different numbers of sodium ions that are co-transported with every glycine molecule) and varying abilities to reverse-transport glycine into the extracellular space. To date, five variants of GlyT1 (GlyT1a, GlyT1b, GlyT1c, GlyT1d, and GlyT1e) and three variants of GlyT2 (GlyT2a, GlyT2b, and GlyT2c) have been identified and occur as a result of alternative promoter usage and/or splicing, but the relative distributions of these within the CNS have not been fully characterized [21].
The essential function of membrane transporters is to accumulate neuromediators in vesicles. At presynaptic terminals, vesicular glutamate transporters (vGluTs; SLC17A7, -6, and -8) load glutamate into synaptic vesicles. The two subtypes of vGluTs, vGluT1, and vGluT2, are expressed in excitatory neurons in a complementary manner in the brain, composing two subsets of excitatory neurons [13]. Glycine also actively accumulates in synaptic vesicles through vesicular inhibitory amino acid transporter (VIAAT); currently, only one type of transporter (SLC32A1) is known to be responsible for this process [18]. The scheme of balanced neuromediator transport is represented in Figure 1.
Membrane carriers are responsible for clearance of glutamate/glycine from interstitial fluid (ISF) in the CNS. The scheme indicates two types of neurons. Some are excitatory and glutamatergic (the upper part of the scheme). Other neurons are inhibitory and glycinergic (the lower part of the scheme). Both types of neurons are interconnected with astrocytes. Moreover, glycine and glutamate are accessible for both types of cells. AA transporters (EAAT, GlyT, etc.) are found in all cell membranes but have differing isoenzyme compositions.
Remarkably, both glutamate and glycine transporters have mechanisms that include sodium ion transport. This means that neuromediator uptake is accompanied by changes in membrane potential. Moreover, the intake of both glutamate and glycine initiates several metabolic reactions in neurons and astrocytes. However, these reactions are spatially distributed, and the fate of the neuromediators is functionally determined by different cells. Interestingly, the metabolic transformations of AAs are closely related to ATP production by mitochondria and the oxidation of glucose.
As mentioned above, any example of metabolic transformation in brain tissue is tightly connected with glycolysis Therefore, glutamate/glycine participation in metabolic pathways seems to be considered correctly including the main neighbor reactions of glucose oxidation. The primary source of energy for the brain is glucose. This sugar is almost entirely oxidized under basal physiological conditions, providing nearly all the energy necessary to support brain function. However, when supplemental energy is needed, necessary energy demands may be provided by other metabolites, such as ketones, fatty acids, acetate, lactate, and certain amino acids [19]. Pyruvate, the end product of aerobic glycolysis, can enter the tricarboxylic acid (TCA) cycle by two different routes: (1) via acetyl-CoA formation, catalyzed by the pyruvate dehydrogenase complex, and (2) by the formation of oxaloacetate, catalyzed by PC [24]. However, the end metabolite of anaerobic glycolysis, lactate, also participates in the energy supply of neurons (Figure 2). Pellerin and Magistretti originally proposed the astrocyte-neuron lactate shuttle (ANLS) model, wherein lactate released from astrocytes serves as a buffer compound in response to a glutamate-induced glycolysis stimulus [25]. Then, lactate is exported to neurons, where it is converted to pyruvate to fuel oxidative phosphorylation.
A scheme of the metabolic pathways involved in general glutamate/glycine transformations. The reactions occur in various intracellular localizations and can be duplicated in different compartments. The main metabolic pathways (glycolysis and the tricarboxylic acid (TCA) cycle) are labeled. The enzyme abbreviations are as follows: GM: glutaminase; GS: glutamine synthetase; GDH: glutamate dehydrogenase; GL: glutamylcysteine ligase; GTS: glutathione synthetase; AG: asparaginase; AT: aminotransferase; PPC: phosphoenolpyruvate carboxykinase; PC: pyruvate carboxylase; PDC: pyruvate dehydrogenase complex; PK: pyruvate kinase; LDH: lactate dehydrogenase; SDH: serine dehydrogenase; STM: serine transhydroxymethylase; and GCS: the glycine cleavage system. Other abbreviations are as follows: NAD+: Nicotinamide adenine dinucleotide (oxidized); NADH: Nicotinamide adenine dinucleotide (reduced); ATP: Adenosine triphosphate; ADP: Adenosine diphosphate; and THF:Tetrahydrofolate.
Thus, the ANLS model suggests that lactate, not glucose, provides energetic support for firing neurons [26]. Glutamate and glycine are active participants in these metabolic processes. Exclusion of most blood-borne glutamate at the blood-brain barrier (BBB) and a net removal of glutamine from the brain indicate that the cerebral pools of glutamate are largely produced within the brain [27]. The stability of glutamate concentration is maintained by two main reactions. Glutamine synthetase (GS), which is found in astrocytes, is the only known enzyme to date that is capable of a reversible conversion between glutamine and glutamate and ammonia in the mammalian brain [28]. Furthermore, cells can convert glutamate to glutamine in an ATP-dependent process catalyzed by glutamine synthetase. Astrocytic uptake of glutamate and release of glutamine, together with neuronal uptake of glutamine and release of glutamate, constitute the glutamate-glutamine cycle [29]. However, much of the glutamate taken up by astrocytes is destined for oxidative degradation, which first requires conversion to the TCA cycle intermediate 2-oxoglutarate. This can take place via transamination by aminotransferase (AT) or via oxidative deamination by glutamate dehydrogenase (GDH) [30].
Once glycine passes into a cell by uptake by GlyTs, the intracellular glycine concentration can be regulated via synthesis from L-serine within the cell, which itself can be synthesized from glycolysis intermediates and L-glutamate [24]. The major pathway for the glycine catabolism involves the oxidative cleavage of glycine to CO2, NH4+, and a methylene group (–CH2–), which is accepted by tetrahydrofolate (H4folate) in a reversible reaction catalyzed by the glycine cleavage system (also called glycine synthase) [31]. The glycine cleavage system is essentially reversible but catalyzes glycine synthesis significantly only under anaerobic conditions, such as in anaerobic bacteria or anaerobic systems in vitro supplemented with NADH+H+ [32].
Taken together, all known information about the metabolic pathways suggests that glutamate and glycine self-regulate the processes of their concentration restoration and mutual transformation. Additionally, oxidative phosphorylation in the mitochondria also plays a key role in the balance of these AAs.
The neuromediator function of AAs in the CNS is performed through the activation of membrane receptors. After being released from the presynaptic membrane into a synaptic cleft, glutamate and glycine rapidly diffuse to a postsynaptic membrane, where appropriate receptors are further activated.
Glutamate receptors are divided into two groups: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). Excitatory neurotransmission throughout the CNS is mediated by ligand-gated ion channels, including ionotropic glutamate receptors (iGluRs) [33]. Abnormalities in iGluRs lead to a wide range of neurological diseases. Glutamate, the primary neurotransmitter in almost all synapses in the CNS, is released from presynaptic terminals and diffuses to the postsynaptic membrane, where it binds to iGluRs. This process leads to the opening of ion channels, allowing cations to flow in. Thus, the transmembrane channel rapidly depolarizes the postsynaptic membrane. The decrease in membrane potential initiates signal transduction in the postsynaptic neuron. In the iGluR family, four subtypes of integral membrane proteins have been identified in vertebrates based on their pharmacological properties and sequence homologies: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate (KA), N-methyl-D-aspartate (NMDA), and δ-receptors [34]. Subsequent cloning studies have revealed that NMDARs are assembled as heteromers that differ in subunit composition. To date, seven different subunits have been identified and categorized into three subfamilies according to sequence homology [35]. Each iGluR family member exhibits specific kinetic and pharmacological properties in addition to playing a unique role in neurotransmission [36]. The iGluRs are ligand-gated ion channels that are permeable to Na+ and K+ (and Ca2+ in some instances), whereas the mGluRs are G protein-coupled receptors that trigger second messenger cascades. The early component and the late component of neurotransmission are assumed to be mediated by AMPARs and NMDARs/KARs, respectively. This assumption is based on receptor kinetics, as AMPARs are faster and NMDARs/KARs are slower. Nevertheless, acoustic signals are transferred by all of these iGluRs in a precise and reliable manner. Moreover, some auditory processing neurons have a fourth type of iGluR, the delta receptor [34]. The open, or conducting, conformation of the iGluR ion channel is nonselective for monovalent cations. Membrane excitation is often driven by channel permeability to Ca2+. This Ca2+ influx and its physiological and pathological consequences depend strongly on the specific iGluR subtype and the specific subunits in its oligomeric complex [37].
mGluRs are G protein-coupled receptors (GPCRs) that, following activation, regulate both G protein-dependent and G protein-independent signalling pathways. According to sequence homology, cell signalling activation, and agonist selectivity, the mGluRs have been divided into eight subtypes (from mGlu1 to mGlu8). These subtypes comprise three different subgroups (from I to III) [38]. Group I mGluRs (mGlu1 and mGlu5) are functionally linked to polyphosphoinositide (PI) hydrolysis and are negatively coupled with K+ channels. Both group II (mGlu2 and mGlu3) and group III (mGlu4, mGlu6, mGlu7, and mGlu8) mGluRs negatively regulate adenylate cyclase and activate mitogen-activated protein kinase (MAPK) and PI-3-kinase pathways [39]. mGluRs are usually localized on synaptic and extrasynaptic membranes in both glia and neurons. Group I mGluRs are generally postsynaptic, surrounding ionotropic receptors, and modulate depolarization and synaptic excitability. Groups II and III are mostly expressed at the presynaptic level and control the release of neurotransmitters [39, 40]. mGluRs are heavily expressed throughout the basal ganglia (BG), where they modulate neuronal excitability, transmitter release, and long-term synaptic plasticity [41]. These receptors are coupled to different G proteins and modulate slow postsynaptic neuronal responses, either through presynaptic or postsynaptic machinery or through modulation of astrocyte function [42]. mGluRs are highly and diffusely expressed in glial cells. On the one hand, this increases the options for therapeutic interventions, but on the other hand, it makes it even more difficult to selectively target single receptors to yield neuroprotection (Figure 3) [43].
A reconstruction of possible AA ionotropic receptors in the CNS. The images were created using the data collected in the Protein Data Bank (PDB) (
Glycine receptors (GlyRs), along with certain γ-aminobutyric acid receptors (GABAARs), are the principal determinants of fast inhibitory synaptic neurotransmission in the central nervous system (CNS). GlyR and GABAAR belong to the superfamily of pentameric ligand-gated ion channels (pLGICs) [33]. The two neurotransmitters (glycine and GABA) may be functionally interchangeable, and the multiple receptor subtypes with inhibitory influences provide diverse mechanisms for maintaining inhibitory homeostasis [35]. Inhibitory glycine receptors (GlyRs) are anion-selective ligand-gated ion channels (LGICs), which, together with GABAA receptors (GABAARs), nicotinic acetylcholine receptors (nAChRs), and serotonin type 3 receptors (5HT-3), form the eukaryotic Cys-loop family [36]. Several endogenous molecules, including neurotransmitters and neuromodulators (such as glutamate, Zn, and Ni), and exogenous substances, such as anaesthetics and alcohols, modulate GlyR function [40].
Despite their obvious physiological roles in protein synthesis, the cellular effects of glycine and glutamate in the CNS seem to be quite different. If glycine has been contemplated an “angel” compound, due to its generally positive effects, then glutamate has usually been considered a “demon” compound, owing to its generally negative effects. Although the last claim is far from accurate, the first is supported by many experimental findings. Indeed, the effect of glycine has always been reported as positive. It protects against oxidative stress caused by a wide variety of chemicals, drugs, and toxicants at the cellular or organ level in the liver, kidneys, intestines, and vascular system [34, 37]. Glycine is a major component of collagen molecules that is vital to stabilizing them to form a triple helix [48]. Administration of glycine attenuates diabetic complications in a streptozotocin-induced diabetic rat model [49]. Supplemental glycine effectively protects muscles in a variety of wasting models, including cancer cachexia, sepsis, and dieting [50]. Glycine may prevent ischaemia–reperfusion injury by direct cytoprotection, presumably by inhibition of the formation of plasma membrane pores and of the inflammatory response [38]. The cytoprotective and modulatory effects of glycine have been observed in many nonneuronal cell types. The action of glycine is mediated by classic or unconventional GlyRs, both inside and outside of the nervous system [51]. Glycine cytoprotection substantially overlaps with the number of agents that act on neuronal receptors with glycine as an agonist or coagonist. This observation has been confirmed by molecular pharmacology studies from multiple laboratories. The studies indicate highly constrained steric and conformational requirements for the interaction, which, along with the rapid on-off timing of the effects, is consistent with the involvement of reversible ligand-binding site interactions [52].
In contrast, glutamate is considered a toxic agent that yields excitotoxicity at overload concentrations. Indeed, the neurotoxic potential of glutamate has been recognized since the 1950s [53]. For example, a major driver of white matter demise is excitotoxicity, a consequence of the excessive glutamate released by vesicular and nonvesicular mechanisms from axons and glial cells. This excessive glutamate concentration results in overactivation of iGluRs profusely expressed by all cell compartments in white matter [54]. Generally, excitotoxicity involves a large inflow of Ca2+ and Na+ into neurons up to the conditions when Ca2+ concentrations reach critical levels, leading to cell injury or death [55]. Moreover, ambient extracellular glutamate is lower than the concentration known to trigger excitotoxicity and subsequent neurodegeneration; excitotoxicity is known to occur at extracellular glutamate concentrations as low as 2 to 5 μM, with swelling and apoptosis predominating at <20 μM glutamate and fast necrosis at >100 μM glutamate [56]. Excitotoxic neuronal death is involved in neurodegenerative diseases of the CNS, such as multiple sclerosis [57], Alzheimer’s disease [58], Parkinson’s disease [59], Huntington’s disease [60], stroke, epilepsy, alcohol withdrawal, and amyotrophic lateral sclerosis [61]. However, the role of glutamate is not only excitotoxic. The assumption that neurodegenerative disease treatments should “fight against” glutamate is incorrect given the wrong function of glutamate in the CNS. As a part of normal physiological excitation, this AA must be properly regulated, but battling with glutamate receptors or the transport system will cause serious negative consequences. Instead, the level and functional activity of glutamate may be adjusted by metabolic processes, including glycine and oxidative phosphorylation, in mitochondria.
Because glutamate is the major mediator of excitatory signals as well as of nervous system plasticity, including cell elimination, it follows that glutamate needs to be present at the right concentrations in the right places at the right time [17]. These conditions are regulated by GS, GM, and EAATs and convectional diffusion in ISF. There is evidence that extracellular glutamate is not compartmentalized by EAATs under some conditions [62]. The most obvious shift in glutamate levels is observed under high GDH and AT activity. The general activation of bioenergetics decreases the excessive glutamate concentration by stimulating the TCA cycle. Moreover, glycine can participate in this shift in a variety of ways. GlyT-1 controls glycine release and reuptake, determines glycine availability at glycine binding sites on NMDA receptors [36] and coordinates neuronal-glial interactions at glutamatergic synapses [19]. Thus, glycine assists glutamate in the activation of astrocytes and further stimulates the mitochondria according to the ANLS hypothesis. Glycine can conjugate with glutamate in the GSH synthesis pathway (Figure 1). This mechanism is essential to maintain the redox status of neurons and to prevent oxidative stress and high levels of reactive oxygen species (ROS) synthesis. Neuronal mitochondria are the target of glutamate, which attenuates succinate dehydrogenase (a key enzyme of the TCA cycle) inhibition by oxaloacetate [63], with further induction of ROS production [64]. However, glycine can prevent excessive hydrogen peroxide production induced by glutamate in brain mitochondria [65], thereby reducing the prooxidant effects of the excessive glutamate concentrations.
Interestingly, the effects of amino acids can vary depending on the species. For example, in a chick model, injections of L-glutamate, NMDA, and AMPA attenuated total distress vocalizations and induced sedation [66]. The association between glutamate and inhibition/sedation is even stronger because the brain contains a considerable level of glutamate decarboxylase, which directly catalyzes the decarboxylation of glutamate to GABA [27]. Additionally, glycine is not always associated with direct inhibition in the CNS. Indeed, in mature neurons, where there is a low intracellular Cl− concentration maintained by K+- Cl− cotransporter 2 (KCC2), activation of GlyRs elicits an influx of Cl−, leading to rapid hyperpolarization and postsynaptic inhibition [67]. In contrast, in immature neurons, activation of GlyRs results in efflux of Cl−, leading to neuronal depolarization; this opens voltage-dependent Ca2+ channels, elicits action potentials, and establishes early network activity and excitation in the developing nervous system [68].
Thus, the balance between excitation and inhibition is the result of continuous interactions among different processes involving both glutamate and glycine. It is essential that the main reactions and regulatory sites are nonhomogenously distributed in neuronal space and are time-regulated. Convective flow does not restore the homogeneity of mediator and metabolite concentrations because of the tortuosity of the system [63]. A scheme of the balanced interactions between glycinergic and glutamatergic synapses is shown in Figure 4.
The transport and activation of receptors in glycinergic and glutamatergic synapses. The transport system is tightly linked with glucose consumption. This transport system occurs in both astrocytes and neurons, but according to the ANLS model, the majority of glucose is consumed in astrocytes, with further diffusion of lactate to neurons. Lactate transport is facilitated by monocarboxylate transporters (MCTs), which have two different isoenzymes. MCT1 is expressed in astrocytes, and MCT2 is found in neurons [
The first (and obvious) clinical application of AAs is as a reference level to indicate different pathologies. This suggestion covers more AAs than those mentioned above. For decades, the biochemical analysis of AAs in body fluids has been an important diagnostic tool in the detection of congenital errors of metabolism. Significant elevations of amino acids in plasma, urine, or CSF have been the backbone of many diagnostic procedures [71]. This is because defects in amino acid catabolic pathways can be detected by the characteristic accumulation of their metabolites. Well-known examples of this are elevated plasma concentrations of phenylalanine in phenylketonuria (PKU) and increased concentrations of homocysteine in homocystinuria [71].
In addition, the properties of glutamate/glycine discussed above indicate a wide range of potential medical applications for compounds that govern transport, receptors, and metabolic systems in the CNS. A classic pharmacological approach may be based on the search for chemicals that affect the indicated processes; interactions with the target protein site or reaction must be local and precisely unidirectional and wide metabolic participation of the candidate should be avoided. There are several examples to date. Each of the three mGlu subgroups can be considered a novel target for the treatment of schizophrenia. All three symptom domains could be effectively treated by mGlu5 positive allosteric modulators, which are devoid of toxicity and seizure liability according to preclinical data. Furthermore, the potential antipsychotic and cognitive-enhancing effects of drugs targeting mGlu1 and mGlu3 were supported by recent genetic investigations of schizophrenia patients [72]. Preclinical studies have revealed that specific mGluR subtypes mediate significant neuroprotective effects that reduce toxin-induced midbrain dopaminergic neuronal death in animal models of Parkinson’s disease [41]. Additionally, mGluRs have emerged as research targets in treating Alzheimer’s disease. In particular, mGluR-based compounds producing both symptomatic and disease-modifying effects in preclinical models of the disease are of special interest [73]. G protein-coupled mGluRs expressed by tumor cells, particularly cancer stem cells, might represent new candidate drug targets for the treatment of malignant brain tumors [74]. Group III mGluR agonists have been recently identified as promising tools for managing affective symptoms, such as the pathological anxiety observed in neuropathic pain. However, the use of mGluR ligands as anxiolytics was disappointing in clinical trials. Nevertheless, there is ground for a certain amount of optimism [75].
Pharmacological modulation of glycinergic inhibition could represent a novel therapeutic strategy for a variety of diseases involving altered synaptic inhibition, primarily in the spinal cord and brain stem but possibly also at supraspinal sites [74]. Among the inhibitors of GlyT-1, two candidates have attracted the most attention. Sarcosine, a known intermediate of glycine metabolism, had positive results as a short-term treatment of major depression and for acutely ill and chronically stable schizophrenia patients. Another GlyT-1 inhibitor, bitopertin, was expected to be effective in treating negative or positive schizophrenia symptoms. However, the phase III clinical trials fell short of the primary endpoint, and the investigation was halted due to its lack of efficacy in improving negative symptoms [76]. Gelsemium, a small genus of flowering plants from the family Loganiaceae, may be used as a pain treatment and for its mechanism of action. Gelsemium and its active alkaloids may produce antinociception by activating the spinal α3 glycine/allopregnanolone pathway in inflammatory, neuropathic, and bone cancer pain without inducing antinociceptive tolerance, in contrast to morphine [75].
Another strategy is to directly use AAs for medical treatment. In this scenario, glycine is the most appropriate candidate. Glycine has a wide spectrum of protective properties against different diseases and injuries. As such, it represents a novel anti-inflammatory, immunomodulatory and cytoprotective agent [77]. Oral supplementation of glycine at a proper dose is very successful in treating several metabolic disorders in individuals with cardiovascular diseases, various inflammatory diseases, cancers, diabetes, and obesity [34]. Glycine was well tolerated at a dose of 0.8 g/kg body weight a day, resulting in significantly increased serum glycine levels and a 7% reduction in negative symptoms in patients with treatment-resistant schizophrenia [78]. An acute high dosage of glycine attenuates the neurophysiological representation of the brain’s preattentive acoustic change detection system (mismatch negativity) in healthy controls, raising the possibility that the optimal effects of glycine and other glycine agonists may depend on the integrity of the NMDA receptor system [79]. The glycine was effective in the treatment of ischaemic stroke patients. In a randomized, double-blind, placebo-controlled study on 200 patients with acute (<6 h) ischaemic stroke in the carotid artery area, 1.0–2.0 g/day of glycine was accompanied by a tendency towards decreased 30-day mortality (5.9% in the 1.0 g/day glycine and 10% in the 2.0 g/day glycine groups vs. 14% in the placebo and 14.3% in the 0.5 g/day glycine groups), an improved clinical outcome on the Orgogozo Stroke Scale (p < 0.01) and the Scandinavian Stroke Scale (p < 0.01) and a favorable functional outcome on the Barthel Index for Activities of Daily Living (p < 0.01) in the 1.0 g/day glycine group compared to those in the placebo group in patients with no or mild disability [80]. The molecular mechanism of such an effect is based on the ability of glycine to initiate stable vasodilatation of arterioles, which has been demonstrated in rat pial vessels and in mesenteric arterioles [81, 82].
According to experimental and clinical evidence, AAs are especially useful nutrients for the treatment of patients with different diseases. These nutrients not only supply a background pool for biochemical reactions, but the functions of the metabolites cover a wide range of neurochemical processes, and they are always mutually dependent. Even though some processes are decreased or increased in illnesses, it does not mean that the treatment strategy must be targeted to only correct the single altered process. A prominent example is glutamate-induced excitotoxicity in neurons. The best strategy to prevent increased glutamate concentrations is to maintain bioenergetic processes in neurons and astrocytes at high activity levels and to activate glycine-dependent processes. Moreover, it helps to assign the exceeded content of the neuromediator to a physiological range and to form stable conditions for further health development, avoiding excitotoxicity (Figure 5). Searching for exogenous antagonists of metabolic receptors seems to be an incorrect therapeutic strategy because the function of the AA-dependent system depends on the basic metabolic regulatory core of metabolic processes. Indeed, to find appropriate therapeutic methods, further fundamental and clinical investigations are necessary.
Scheme of the mutual influence of inhibition and excitation mediated by glycine and glutamate.
The author has no conflict of interest to declare.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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The ability to measure and predict business cycles, taking into account their mutual influence, is a prerequisite for the development of an adequate business policy of countries and their associations.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Elena Zarova",authors:null},{id:"54366",title:"Solution of Differential Equations with Applications to Engineering Problems",slug:"solution-of-differential-equations-with-applications-to-engineering-problems",totalDownloads:6866,totalCrossrefCites:5,totalDimensionsCites:8,abstract:"Over the last hundred years, many techniques have been developed for the solution of ordinary differential equations and partial differential equations. 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After that, the readers are introduced to two major numerical methods commonly used by the engineers for the solution of real engineering problems.",book:{id:"5513",slug:"dynamical-systems-analytical-and-computational-techniques",title:"Dynamical Systems",fullTitle:"Dynamical Systems - Analytical and Computational Techniques"},signatures:"Cheng Yung Ming",authors:[{id:"191017",title:"Dr.",name:"Cheng",middleName:null,surname:"Y.M.",slug:"cheng-y.m.",fullName:"Cheng Y.M."}]},{id:"56538",title:"Stochastic Resonance and Related Topics",slug:"stochastic-resonance-and-related-topics",totalDownloads:1718,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The stochastic resonance (SR) is the phenomenon which can emerge in nonlinear dynamic systems. In general, it is related with a bistable nonlinear system of Duffing type under additive excitation combining deterministic periodic force and Gaussian white noise. It manifests as a stable quasiperiodic interwell hopping between both stable states with a small random perturbation. Classical definition and basic features of SR are regarded. The most important methods of investigation outlined are: analytical, semi-analytical, and numerical procedures of governing physical systems or relevant Fokker-Planck equation. Stochastic simulation is mentioned and experimental way of results verification is recommended. Some areas in Engineering Dynamics related with SR are presented together with a particular demonstration observed in the aeroelastic stability. Interaction of stationary and quasiperiodic parts of the response is discussed. Some nonconventional definitions are outlined concerning alternative operators and driving processes are highlighted. The chapter shows a large potential of specific basic, applied and industrial research in SR. This strategy enables to formulate new ideas for both development of nonconventional measures for vibration damping and employment of SR in branches, where it represents an operating mode of the system itself. Weaknesses and empty areas where the research effort of SR should be oriented are indicated.",book:{id:"6128",slug:"resonance",title:"Resonance",fullTitle:"Resonance"},signatures:"Jiří Náprstek and Cyril Fischer",authors:[{id:"207472",title:"Dr.",name:"Jiri",middleName:null,surname:"Naprstek",slug:"jiri-naprstek",fullName:"Jiri Naprstek"},{id:"213311",title:"Dr.",name:"Cyril",middleName:null,surname:"Fischer",slug:"cyril-fischer",fullName:"Cyril Fischer"}]}],onlineFirstChaptersFilter:{topicId:"15",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83034",title:"Optimal N-of-1 Clinical Trials for Individualized Patient Care and Aggregated N-of-1 Designs",slug:"optimal-n-of-1-clinical-trials-for-individualized-patient-care-and-aggregated-n-of-1-designs",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106352",abstract:"Precision medicine typically refers to the use of genomic signatures of patients to assign more effective therapies to treat patients, or, for improved diagnosis of the early onset of a disease so that interventions can be delivered to prevent or delay the disease progression. Because the aim is to provide individualized patient treatment, such single-person trials are called N-of-1 trials. This chapter reviews fundamental ideas, models, and construction of optimal designs for N-of-1 trials, which are invariably constructed from crossover trials, where each patient receives a random sequence of trial treatments over time. 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Then, it is investigated that quasi conformally flat quasi Einstein-Weyl manifolds are of quasi constant curvature, recurrent and semi-symmetric under which conditions after obtaining the expression of the curvature tensor of the quasi conformally flat quasi Einstein-Weyl manifold. Furthermore, some equivalences are obtained between to be of quasi constant curvature and to be semi-symmetric in quasi conformally flat quasi Einstein-Weyl manifolds.",book:{id:"11502",title:"Manifolds - Recent Developments and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11502.jpg"},signatures:"Fusun Nurcan"},{id:"82970",title:"Probability to be Involved in a Road Accident: Transport User Socioeconomic Approach",slug:"probability-to-be-involved-in-a-road-accident-transport-user-socioeconomic-approach",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.106325",abstract:"Road education is one of the most relevant issues focused to reduce traffic accidents, so it is important to analyze the driver’s behavior on the roads. International research has found evidence for a relationship between socioeconomic characteristics and traffic accidents. In this sense, the chapter shows a methodology to estimate the probability to be involved in a road accident, considering the road education and the socioeconomic characteristics of the population of a specific region, taking the Santiago de Querétaro city (in México) as a study case. Through a logit model estimation and a survey applied to pedestrian, cyclist, motorcyclist, car driver, and freight driver allow us to determine which socioeconomic variables and road education are significant to determine the probability of being involved in a road accident.",book:{id:"12021",title:"Applied Probability Theory - New Perspectives, Recent Advances and Trends",coverURL:"https://cdn.intechopen.com/books/images_new/12021.jpg"},signatures:"Saúl Antonio, Obregón Biosca, José Luis Reyes Araiza and Miguel Angel Pérez Lara y Hernández"},{id:"82947",title:"Some Tauberian Theorems under Triple Statistically Nörlund-Cesáro Summability Method",slug:"some-tauberian-theorems-under-triple-statistically-n-rlund-ces-ro-summability-method",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106141",abstract:"In this paper, we extend the notion presented by Braha (2020) in a higher dimension, we introduce the notion of Np,qn,m,gCn,m,g1,1,1-statistically convergence and show necessity and sufficiency conditions under which the existence of the limit st-limn,m,g→∞xn,m,g=L follows from that st-limn,m,g→∞Np,qn,m,gCn,m,g1,1,1=L. These conditions are one-sided or two-sided if xn,m,g is a sequence of real or complex numbers, respectively.",book:{id:"11503",title:"Functional Calculus - Recent Advances and Development",coverURL:"https://cdn.intechopen.com/books/images_new/11503.jpg"},signatures:"Carlos Granados"},{id:"82847",title:"A Chaos Auto-Associative Model with Chebyshev Activation Function",slug:"a-chaos-auto-associative-model-with-chebyshev-activation-function",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106147",abstract:"In this work, we shall put forward a novel chaos memory retrieval model with a Chebyshev-type activation function as an artificial chaos neuron. According to certain numerical analyses of the present association model with autocorrelation connection matrix between neurons, the dependence of memory retrieval properties on the initial Hamming distance between the input pattern and a target pattern to be retrieved among the embedded patterns will be presented to examine the retrieval abilities, i.e. the memory capacity of the associative memory.",book:{id:"12019",title:"Chaos Theory - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/12019.jpg"},signatures:"Masahiro Nakagawa"},{id:"82826",title:"A Brief Look at the Calderón and Hilbert Operators",slug:"a-brief-look-at-the-calder-n-and-hilbert-operators",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106027",abstract:"The Calderón operator is the sum of the Hardy averaging operator and its adjoint, and plays an important role in the theory of real interpolation. On the other hand, the Hilbert operator arises from the continuous version of Hilbert’s inequality. Both operators appear in different contexts and have numerous applications within harmonic analysis. In this chapter we will briefly review the Calderón and Hilbert operators, showing some of the most relevant results within functional analysis and finally we will present recent results on these operators within Fourier analysis.",book:{id:"11503",title:"Functional Calculus - Recent Advances and Development",coverURL:"https://cdn.intechopen.com/books/images_new/11503.jpg"},signatures:"Guillermo J. 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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. 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His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. 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Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. 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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:21,paginationItems:[{id:"83000",title:"Purine and Pyrimidine Pathways as Antimalarial Targets",doi:"10.5772/intechopen.106468",signatures:"Yacoba V.T. Minnow and Vern L. 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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. 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Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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He has published more than 190 research papers and authored five books.",institutionString:"Yunnan University",institution:{name:"Yunnan University",country:{name:"China"}}},{id:"1177",title:"Prof.",name:"António",middleName:"J. R.",surname:"José Ribeiro Neves",slug:"antonio-jose-ribeiro-neves",fullName:"António José Ribeiro Neves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1177/images/system/1177.jpg",biography:"Prof. António J. R. Neves received a Ph.D. in Electrical Engineering from the University of Aveiro, Portugal, in 2007. Since 2002, he has been a researcher at the Institute of Electronics and Informatics Engineering of Aveiro. Since 2007, he has been an assistant professor in the Department of Electronics, Telecommunications, and Informatics, University of Aveiro. He is the director of the undergraduate course on Electrical and Computers Engineering and the vice-director of the master’s degree in Electronics and Telecommunications Engineering. He is an IEEE Senior Member and a member of several other research organizations worldwide. His main research interests are computer vision, intelligent systems, robotics, and image and video processing. He has participated in or coordinated several research projects and received more than thirty-five awards. He has 161 publications to his credit, including books, book chapters, journal articles, and conference papers. He has vast experience as a reviewer of several journals and conferences. As a professor, Dr. Neves has supervised several Ph.D. and master’s students and was involved in more than twenty-five different courses.",institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"11317",title:"Dr.",name:"Francisco",middleName:null,surname:"Javier Gallegos-Funes",slug:"francisco-javier-gallegos-funes",fullName:"Francisco Javier Gallegos-Funes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/11317/images/system/11317.png",biography:"Francisco J. Gallegos-Funes received his Ph.D. in Communications and Electronics from the Instituto Politécnico Nacional de México (National Polytechnic Institute of Mexico) in 2003. He is currently an associate professor in the Escuela Superior de Ingeniería Mecánica y Eléctrica (Mechanical and Electrical Engineering Higher School) at the same institute. His areas of scientific interest are signal and image processing, filtering, steganography, segmentation, pattern recognition, biomedical signal processing, sensors, and real-time applications.",institutionString:"Instituto Politécnico Nacional",institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"428449",title:"Dr.",name:"Ronaldo",middleName:null,surname:"Ferreira",slug:"ronaldo-ferreira",fullName:"Ronaldo Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428449/images/21449_n.png",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour, MS, Ph.D., is currently with the Department of Research and Evaluation, Kaiser Permanente Southern California. He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. 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:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{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:"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:'"Politechnica" University Timişoara',institution:null},{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:{name:"Tecnalia",country:{name:"Spain"}}},{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:"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:null,institution:null},{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:"417317",title:"Mrs.",name:"Chiedza",middleName:null,surname:"Elvina Mashiri",slug:"chiedza-elvina-mashiri",fullName:"Chiedza Elvina Mashiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"352140",title:"Dr.",name:"Edina",middleName:null,surname:"Chandiwana",slug:"edina-chandiwana",fullName:"Edina Chandiwana",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"342259",title:"B.Sc.",name:"Leonard",middleName:null,surname:"Mushunje",slug:"leonard-mushunje",fullName:"Leonard Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"347042",title:"Mr.",name:"Maxwell",middleName:null,surname:"Mashasha",slug:"maxwell-mashasha",fullName:"Maxwell Mashasha",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"2941",title:"Dr.",name:"Alberto J.",middleName:"Jorge",surname:"Rosales-Silva",slug:"alberto-j.-rosales-silva",fullName:"Alberto J. Rosales-Silva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"437913",title:"Dr.",name:"Guillermo",middleName:null,surname:"Urriolagoitia-Sosa",slug:"guillermo-urriolagoitia-sosa",fullName:"Guillermo Urriolagoitia-Sosa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"435126",title:"Prof.",name:"Joaquim",middleName:null,surname:"José de Castro Ferreira",slug:"joaquim-jose-de-castro-ferreira",fullName:"Joaquim José de Castro Ferreira",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"437899",title:"MSc.",name:"Miguel Angel",middleName:null,surname:"Ángel Castillo-Martínez",slug:"miguel-angel-angel-castillo-martinez",fullName:"Miguel Angel Ángel Castillo-Martínez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"289955",title:"Dr.",name:"Raja",middleName:null,surname:"Kishor Duggirala",slug:"raja-kishor-duggirala",fullName:"Raja Kishor Duggirala",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jawaharlal Nehru Technological University, Hyderabad",country:{name:"India"}}}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",slug:"hitoshi-tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",slug:"marcus-vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",slug:"ramana-vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},onlineFirstChapters:{paginationCount:7,paginationItems:[{id:"83087",title:"Role of Cellular Responses in Periodontal Tissue Destruction",doi:"10.5772/intechopen.106645",signatures:"Nam Cong-Nhat Huynh",slug:"role-of-cellular-responses-in-periodontal-tissue-destruction",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Periodontology - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11566.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"82654",title:"Atraumatic Restorative Treatment: More than a Minimally Invasive Approach?",doi:"10.5772/intechopen.105623",signatures:"Manal A. 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