HIF1 targets genes that regulate lipid metabolism.
\r\n\tThis book will aim to survey the most recent diagnostic techniques as well as the most promising therapeutic options we can count on to deal with optic nerve disorders. The audience of the book is quite wide and it aims at being the main entry to this fascinating topic for students, clinicians, and researchers.
",isbn:"978-1-80356-774-7",printIsbn:"978-1-80356-773-0",pdfIsbn:"978-1-80356-775-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"e3d02512ccae0638a73c5c2839e50015",bookSignature:"Prof. Felicia M. Ferreri",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11704.jpg",keywords:"Toxic Neuropathy, Ethambutol, Methanol, Leber Neuropathy, Congenital Anomalies, Coloboma, Optic Disc Excavation, Systemic Anomalies, Optic Disc Swelling, Anterior ION, Posterior ION, ION Variants",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 25th 2022",dateEndSecondStepPublish:"June 2nd 2022",dateEndThirdStepPublish:"August 1st 2022",dateEndFourthStepPublish:"October 20th 2022",dateEndFifthStepPublish:"December 19th 2022",remainingDaysToSecondStep:"17 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Prof. Felicia M. Ferreri graduated summa cum laude from the University of Messina, Italy in 1998. She served as co-investigator for many national and international clinical trials. Since 2002, she is an Assistant Professor in Ophthalmology at the University of Messina",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"32442",title:"Prof.",name:"Felicia M.",middleName:null,surname:"Ferreri",slug:"felicia-m.-ferreri",fullName:"Felicia M. Ferreri",profilePictureURL:"https://mts.intechopen.com/storage/users/32442/images/system/32442.png",biography:"Felicia M. Ferreri graduated summa cum laude from the University of Messina, Italy, in 1998 and completed her ophthalmology residency at the Policlinico Universitario, Messina, in 2002. She interned at the Corneal Section of San Raffaele Hospital in Milan and at the Pediatric Ophthalmology Diseases Section of Hospital Careggi in Florence. She spent research periods at Virginio del Rocio hospital in Seville, San Carlos hospital in Madrid, the Royal Bolton Hospital in Manchester, and Universidade Fluminense in Rio de Janeiro. 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Adaptation to hypoxia involves hypoxia‐inducible factor 1 (HIF1) and requires reprogramming of essential elements of cellular metabolism [6]. HIF1 was described about 20 years ago [7]. It is a heterodimeric transcription factor that is composed of an oxygen‐regulated HIF1α subunit and a constitutively expressed HIF1β subunit [7, 8]. HIF1α is mainly regulated by protein degradation. Under normoxic conditions, HIF1α is subjected to oxygen‐dependent hydroxylation by three prolyl hydroxylase domain proteins (PHD1–3) on two proline residues in the oxygen‐dependent degradation (ODD) domain [9]. The prolyl‐hydroxylated HIF1α is targeted for degradation by the tumor suppressor protein von Hippel‐Lindau (VHL), an E3 ubiquitin‐protein ligase [10, 11]. HIF1α is also regulated in an oxygen‐dependent manner by factor inhibiting HIF1 (FIH1) [12, 13]. In this case, FIH1 mediates the hydroxylation of an asparagine residue in the C‐terminal trans‐activation domain, which prevents the binding of HIF1α with coactivators p300 and CBP [13–15]. Hydroxylation of proline and asparagine is inhibited under hypoxic conditions causing HIF1α to rapidly accumulate [12, 13]. HIF1α subsequently heterodimerizes with HIF1β, and the complex binds to hypoxic responsive elements (HREs) within the promoter regions of target genes, and allows for recruitment of coactivators and activation of transcription [16]. In addition to hypoxia, HIF1 accumulation can also be induced by growth‐factor stimulation, gene mutations, and intermediate metabolites [17] (Figure 1).
\nRegulation of HIF1 and its downstream roles related to lipid metabolism. HIF1 accumulation can be induced by hypoxia, gene mutations, intermediate metabolites, and growth factors. HIF1 plays a pivotal role in lipid metabolism. It can increase lipid uptake and trafficking, fatty acid synthesis, sterol synthesis, TAG synthesis, lipid droplet biogenesis, and lipid signal production, and suppress fatty acid β‐oxidation. Lipid droplet accumulation may be the final result of HIF1 in lipid metabolism. It is unclear about its role in phospholipids metabolism.
It has been reported that HIF1 regulates the transcription of hundreds of genes involving many aspect of biology, especially energy metabolism and vascularization [16]. The role of HIF1 in glucose metabolism had been well established [17]. Most of genes involving glucose uptake and glycolysis are directly regulated by HIF1 [17]. Recent studies demonstrated that HIF1 also plays an important role in lipid metabolism [1, 2, 18–21]. Currently, our understanding of HIF1 in regulating lipid metabolism has lagged behind that of glucose metabolism. Lipids, structurally and functionally important in all organisms, are not only one of the major components of cellular membrane systems, but also the source of energy storage. Moreover, signal molecules, such as prostaglandin E2 (PGE2), hydroxyeicosatetraenoic acid (HETE), and steroid hormones, are derived from lipids. This review would focus on the HIF1\'s activity related to dysregulation of lipid metabolism in several diseases, including atherosclerosis [4], fatty liver disease (FLD) [19], heart failure diseases [5], obesity [3], and cancer [1, 2] as well as the involvement of HIF1 in lipid metabolism, including lipid uptake and trafficking, fatty acid metabolism, sterol metabolism, triacylglycerol (TAG) synthesis, phospholipid metabolism, lipid droplet (LD) biogenesis, and lipid signaling.
\nMost of the studies have demonstrated that HIF1\'s activity is associated with lipid accumulation positively [3, 18, 20–27], while few researches have indicated the opposite effect [28–31]. PHD2 inhibition or deletion, increasing HIF1\'s activity (Figure 1), decreased lipid accumulation in different animal models [28, 30, 31]. It indicated that the role of HIF1 in lipid metabolism may be different in different animal models. Details were described and discussed in the following sections.
\nHypoxia has been demonstrated in atherosclerotic plaques [4]. Arterial wall hypoxia exists in a rabbit atherosclerosis injury model [32–34], confirmed in rabbit atherosclerotic plaques [35, 36] as well as in several mouse models [23, 37, 38]. Recently, in vivo studies have demonstrated hypoxia in human atherosclerotic plaques [39]. Macrophages are the major cell types in human plaques that display signs of hypoxia. TAG‐loaded foam cells derived from macrophages are characteristic of both early and late atherosclerotic plaques [40, 41]. Exposure of human macrophages to hypoxia causes an accumulation of TAG‐containing lipid droplets [42]. HIF1α is expressed in various cell types of atherosclerotic lesions and is associated with lesional inflammation [43]. Knockdown of HIF1α with small interfering RNAs inhibits TAG‐loaded foam cell formation in the human monoblastic cell line U937 [22]. Dyslipidemia are regarded as the key risk factors for the development of atherosclerosis, and HIF1 has been suggested to have both detrimental and beneficial roles in atherosclerosis [28, 44, 45]. In murine atherosclerosis, the hypoxia‐induced accumulation of cholesterol was substantially reversed in vitro by reducing the expression of the HIF1α [23]. While in another model, PHD2 inhibition stabilized HIF1α and reduced serum cholesterol levels in low‐density lipoprotein receptor‐deficient mice that were fed a high‐fat diet (HFD) [28]. So the role of HIF1 should be further studied in atherosclerosis lipid metabolism.
\nIschemic heart disease, systemic hypertension, and pathological cardiac hypertrophy eventually result in heart failure. Myocardial hypoxia has been associated with these clinical conditions [25, 46]. Several studies showed a correlation between TAG accumulation and heart failure [26, 47–49]. Hypoxia promotes TAG accumulation in cardiomyocytes [48, 50]. Overexpression of the constitutive active form of HIF1α in cardiomyocytes promotes intracellular lipid accumulation under normoxia [24]. The specific deletion of VHL in mice cardiac myocytes results in lipid accumulation [25, 26]. In a pathological cardiac hypertrophy mouse model, cardiac TAG accumulation in ventricles was abolished in HIF1α knockout mice [26].
\nLipid accumulation is a common feature of fatty liver disease, whether it is alcoholic (AFLD) or nonalcoholic (NAFLD) [19]. FLD initially begins with simple hepatic steatosis, but can irreversibly progress to steatohepatitis, fibrosis, cirrhosis, or hepatocellular carcinoma [19]. Hypoxia in liver has been documented in vivo in rats on a continuous ethanol diet at a constant rate for prolonged periods [51–54]. Recent studies have demonstrated that hypoxia is also observed in NAFLD [55]. Indeed, HIF1 expression is increased in fatty liver diseases [19]. Nath and his colleagues found that ethanol feeding resulted in liver steatosis in wild‐type mice compared with isocaloric diet‐fed controls [27]. Constitutive activation of HIF1α in hepatocytes accelerates lipid accumulation with chronic ethanol feeding compared with wild‐type mice [27]. In contrast, hepatocyte‐specific deletion of HIF1α protected mice from alcohol‐induced liver lipid accumulation [27]. However, another group reported that hepatocyte‐specific HIF1α‐null mice developed severe hyper‐triglyceridemia with enhanced lipid accumulation in the liver of mice after 4 weeks of exposure to a 6% ethanol‐containing liquid diet [29]. Different genetic techniques used to create specific gene expression or knockout mice in each of these studies may offer some explanation of the different results each described. The other possible explanation is that the presence of inflammation may rewire the HIF‐1 pathway, which leads to a different gene expression profile compared to that observed in simple steatosis [19].
\nHypoxia has been directly demonstrated in adipose tissue of several obese mouse models, such as ob/ob mice [56, 57], KKAy obese mice [58], and high‐fat diet‐induced obese mice [56–58]. In HFD‐induced obese mice, HIF1 activation in visceral white adipocytes is critical to maintain dietary obesity [3] and adipocyte‐specific HIF1β or HIF1α knockout mice exhibit reduced fat formation compared with wild‐type controls [59]. Conversely, another group, using transgenic mice with adipose tissue selective expression of a dominant negative version of HIF1, found that mice with inhibition of HIF1\'s activity developed a more severe obesity in HFD‐induced obese mice [60]. Inactivation of PHD2 resulted in the activation of HIF1. Transgenic mice with PHD2‐specific deletion in adipocyte were resistant to HFD‐induced obesity and decreased lipid accumulation [30]. In another PHD2‐deficient mice model, they also had improved glucose tolerance and insulin sensitivity. Whether fed normal chow or HFD, PHD2 inhibition had less adipose tissue, smaller adipocytes, and less adipose tissue inflammation than their littermates. In addition, serum cholesterol level and de novo lipid synthesis were decreased, and the mice were protected against hepatic steatosis in PHD2‐deficient mice [31]. It seems that HIF1 in adipocyte of obesity had different effect on lipid metabolism compared with other models. Thus, the effect of HIF1 in lipid metabolism of obesity has yet to be defined.
\nHypoxia in the tumor microenvironment leads to the metabolic changes in cancer cells. Over 50% cellular energy is produced by glycolysis and HIF1 plays a central role in the changes [16, 61]. Recently disorders of lipid metabolism had been demonstrated in solid tumors [62, 63], such as pancreatic cancer [64], liver cancer [1], breast cancer [65], colon cancer [66], and ovarian cancer [67]. Lipid accumulation is observed in human tumor tissue [66, 68]. Accumulation of cholesterol also has been reported in prostate cancer [69]. Indeed, recent researches had demonstrated that HIF1\'s activity is really involved abnormal lipid metabolism of cancer cells. Hypoxia‐induced lipid accumulation depends on HIF1\'s activity in cancer cells [18, 20, 21]. Under hypoxic condition, the flux from glutamine into fatty acid is mediated by reductive carboxylation, and HIF1α plays an important role in this metabolic shift in tumor cells [70]. HIF1α also inhibits fatty acid β‐oxidation to promote lipid accumulation in human hepatocellular carcinoma [1]. Valli and his colleagues revealed that hypoxia induced many changes in lipid metabolites. Enzymatic steps in fatty acid synthesis and the Kennedy pathway were modified in an HIF1α‐dependent fashion in HCT116 cell line [2]. However, the role of HIF1 in cancer lipid metabolism has not been well addressed, so more researches should be further studied.
\nLipid metabolism is more complicated than glucose metabolism. Besides as major components of membrane, lipids are also a source of energy storage and signal molecules. HIF1‐induced genes involving lipid metabolism are listed in Table 1. We would discuss the role of HIF1 in lipid metabolism from the following linked aspects: lipid uptake and trafficking, fatty acid metabolism, sterol metabolism, TAG synthesis, phospholipids metabolism, lipid droplets biogenesis, and lipid signaling (Figure 1).
\n\nAt the plasma membrane, uptake of fatty acid is mainly regulated by the fatty acid transport protein family, such as CD36 [89–91], and plasma membrane‐associated fatty‐acid‐binding proteins (FABPs). Fatty acid transporter CD36 transports long chain fatty acid (LCFA) across plasma membrane. In cardiac myocytes, acute hypoxia (15 min) induced the redistribution of CD36 from an intracellular pool to the plasma membrane [92]. Similarly, in intact Langendorff‐perfused heart, a similar effect was demonstrated [92]. Thus, indicating the increased intracellular lipid accumulation in hypoxic hearts is attributable to accumulation of fatty acid in the heart [92]. CD36 also can be regulated at the transcriptional level. In neonatal mouse cardiac myocytes, phenyl‐epinephrine (PE) induced free fatty acid uptake in an HIF1α ‐dependent fashion while inhibition of CD36 led to decreased TAG accumulation upon PE stimulation [26]. In this model, CD36 was induced through HIF1‐PPARγ axis [26]. In human retinal pigment epithelial cells, CD36 is mediated by HIF1 binding on its promoter region [71]. Hypoxia also markedly induced CD36 mRNA in corneal and retinal tissue in in vivo [71].
\nProducts of HIF1\'s target genes | \nFunctions in lipid metabolism | \nReferences | \n
---|---|---|
CD36, PPARγ, FABP3, FABP7 | \nFatty acid uptake | \n[21, 26, 71] | \n
VLDLR, LRP1 | \nLDL and VLDL uptake | \n[18, 48, 72, 73] | \n
CAV1, RAB20 | \nEndocytosis and lipid trafficking | \n[74, 75] | \n
PPARα*, TWIST1, Sirt2* | \nFatty acid β‐oxidation | \n[3, 76, 77] | \n
DEC1 | \nFatty acid synthesis | \n[30, 78] | \n
ABCA1* | \nCholesterol efflux | \n[79] | \n
PPARγ, Lipin1 | \nTAG synthesis | \n[20, 26] | \n
CHKA | \nPhospholipids synthesis | \n[80, 81] | \n
ADRP, HIG2, CAV1 | \nLipid droplet biogenesis | \n[42, 74, 82–85] | \n
COX2, PTGES1 | \nLipid signaling | \n[86–88] | \n
HIF1 targets genes that regulate lipid metabolism.
FABPs are part of a larger family of cytoplasmic proteins comprising nine members (FABP1–FABP9) [93], and are involved in reversibly binding intracellular hydrophobic ligands and trafficking them throughout cellular compartments [89]. Some evidence suggested that FABPs could interact directly with CD36 [94]. In
LDL and VLDL are major source of extracellular lipid, and HIF1 has been implicated in the transport of LDL and VLDL into cells. LDL receptor (LDLR) and VLDL receptor (VLDLR) are major receptors that are responsible for LDL and VLDL uptake. It had been reported that hypoxia significantly increased LDL uptake and enhances lipid accumulation in arterial smooth muscle cells (SMCs), exclusive LDLR activity [100]. In addition, hypoxia increased VLDL uptake in cardiac myocytes, which might be partially dependent on up‐regulating VLDLR expression [101]. Some studies had also reported that VLDLR could be induced under hypoxia [102]. In human cancer cell lines, we had demonstrated that HIF1‐mediated VLDLR induction influenced intracellular lipid accumulation through regulating LDL and VLDL uptake under hypoxia [18]. In hepatocellular carcinoma, expression of VLDR was associated positively with HIF1 [18]. In mice, hypoxia‐induced VLDLR expression in HL‐1 cells was dependent on HIF1α through its interaction with an HRE in the
Low‐density lipoprotein receptor related protein 1 (LRP1) belongs to LDL receptor superfamily, and is a key receptor for selective cholesterol uptake in human vascular smooth muscle cells (VSMCs). Hypoxia increased LRP1 expression through HIF1α, and overexpression of LRP1 mediated hypoxia‐induced aggregated LDL (agLDL) uptake in human VSMCs [72] as well as VLDL‐cholesteryl ester (VLDL‐CE) uptake in neonatal rat ventricular myocytes (NRVMs) [73]. In contrast to the strong impact of LRP1 inhibition on VLDL‐CE uptake in hypoxic cardiomyocytes, LRP1 deficiency did not exert any significant effect on VLDL‐TG uptake or VLDL‐TG accumulation [73]. This indicated that VLDLR might be a key receptor for VLDL‐TG uptake. Therefore, more experiments should be done to value the precise contribution of VLDLR and LRP1 in myocardial VLDL‐CE and VLDL‐TG uptake in pathophysiological situation in the heart.
\nLDL and VLDL uptake are through vesicular transport pathways [103]. The LDL receptor superfamily has NPXY motif in cytoplasmic domain that interacts with the endocytotic machinery to mediate rapid clathrin‐dependent endocytosis of the receptor‐ligand complex [104, 105]. Caveolaes are formed in the process of receptor‐mediated endocytosis. Numerous proteins are involved in caveolae formation, including caveolins, Rabs, VAT‐1, SNAP, and VAMP [106]. Caveolin‐1 (CAV1) is an essential structural constituent of caveolae that is involved in constitutive endocytic vesicular trafficking. Loss of VHL function, an E3 ligase involving HIF1α degradation, was associated with increased caveolae formation [74]. CAV1, as a direct target of HIF1, accentuated the formation of caveolae [74]. Knockdown expression of CAV1 inhibited uptake of oxidized LDL (oxLDL) without changing its binding to the plasma membrane [107]. These results indicated that CAV1 was part of the pathway that allowed cells to take up oxLDL [107]. Rab20, a member of the Rab family of small GTP‐binding proteins, regulating intracellular trafficking and vesicle formation, had also been characterized as an HIF‐1 target [75]. Although there was no direct evidence of the involvement of CAV1 and Rab20 in hypoxia‐induced LDL and VLDL uptake, we hypothesized that they might play role in hypoxia‐induced LDL and VLDL uptake and/or intracellular lipid trafficking.
\nTaken together, HIF1 promoting lipid accumulation may increase lipid uptake and intracellular lipid trafficking by inducing related genes directly. It should be further studied if there are more genes targeted by HIF1 in the process.
\nHypoxia increased intracellular lipid accumulation through suppression of fatty acid β‐oxidation (FAO) in several models, and the molecular mechanism involvement of HIF1 in the process had been demonstrated (Figure 2). Under hypoxic condition, human macrophages showed in an increased TAG accumulation that was associated with a decreasing rate of FAO. The decreasing rate of FAO was shown to be partly dependent on the reduced expression of enzymes involved in FAO [42]. Peroxisome proliferator‐activated receptors (PPARs), including α, γ, and β/δ, belong to the nuclear receptor family of ligand‐activated transcription factors that were originally described as gene regulators of various metabolic pathways. PPARα and PPARβ/δ control expression of genes implicated in FAO. PPARγ, in contrast, is a key regulator of glucose homeostasis and adipogenesis [108].
\nThe molecular mechanism involving HIF1 repression of fatty acid β‐oxidation. HIF1 targets PPARα, PPARδ, and Sirt2 directly and thereby suppresses the genetic expression of fatty acid β‐oxidation.
Muscle carnitine palmitoyltransferase 1 (M‐CPT1), a known PPARα target gene, catalyzes the rate‐limiting step in the mitochondrial import of fatty acids for the FAO cycle [109]. In cardiomyocytes, hypoxia and adenovirus‐mediated expression of a constitutively active form of HIF1α reduced the mRNA and protein levels of PPARα and M‐CPT1 [24, 50, 110] as well as the DNA binding activity of PPARα [24, 50]. CoCl2 treatment also decreased PPARα and M‐CPT1 mRNA levels [110]. In intestinal epithelial cells, hypoxia rapidly down‐regulated PPARα mRNA and protein in an HIF1‐dependent manner in vitro and in vivo [76]. HIF1 could down‐regulate PPARα directly through binding a functional HRE in the promoter region [76]. These results suggested that the mechanism of HIF‐1 suppression of FAO involved the partial reduction of the expression of PPARα and M‐CPT1.
\nHIF1 also suppressed FAO by inhibition of PPARδ\'s activity. In a pathological cardiac hypertrophy mouse model, myocardial hypoxia provoked Dnm3os activation and concomitantly mir‐199a and mir‐214 expression through the HIF1‐TWIST1 axis [49]. TWIST1 is a direct target gene of HIF1 [77]. DNM3os is a noncoding RNA transcript that harbors the mi‐RNA cluster mir‐199a∼214, for which PPARδ is a target. Increased expression of mir‐199a and mir‐214 decreased cardiac PPARδ expression and mitochondrial fatty acid oxidative capacity. Reduced expression of enzymes involved in FAO, for example long-chain acyl-CoA dehydrogenase (LCAD) and medium-chain acyl-CoA dehydrogenase (MCAD), was also observed. Conversely, antagomir‐based silencing of miR‐199a∼214 in mice subjected to pressure overload de‐repressed cardiac PPARδ, LCAD and MCAD levels, and restored mitochondrial FAO [49].
\n\nPPARγ coactivator 1α (PGC‐1α) has been prominently associated with the expression of the genes involving FAO and energy expenditure [111]. In obese mouse model, HIF1α suppressed FAO in visceral white adipocytes, in part, through transcriptional repression of sirtuin 2 (Sirt2), an NAD+‐dependent deacetylase [3]. Reduced Sirt2 function directly translated into diminished deacetylation of PGC1α and the expression of FAO genes. HIF1α negated adipocyte‐intrinsic pathway of fatty acid catabolism by negatively regulating the Sirt2‐PGC1α regulatory axis [3].
\nPPARγ coactivator 1β (PGC‐1β) is a transcription factor that also plays critical roles in regulating mitochondrial function and lipid metabolism [112, 113]. PGC‐1β could regulate FAO through activating medium‐chain acyl‐CoA dehydrogenase (MCAD) and long‐chain acyl‐CoA dehydrogenase (LCAD), which catalyzes the first step of FAO in mitochondria [1, 112]. It had been documented previously that hypoxia inhibited PGC‐1β activity through HIF1‐dependent c‐Myc suppression in VHL‐null RCC4 renal carcinoma cells [114]. Under hypoxic condition in Hep3B and HepG2 cells, and also in PC3 prostate cancer cells, Huang and his colleagues revealed a role of the HIF1/C‐MYC/PGC‐1β regulatory axis in hypoxia‐mediated regulation of MCAD and LCAD by which HIF1 suppressed FAO [1]. This study confirmed that hypoxia inhibited FAO in an HIF1‐dependent mechanism in cancer cells [1].
\nIn summary, it had been confirmed by different models that hypoxia inhibits FAO depending on HIF1\'s activity (Figure 2). However, HIF1 did not target FAO‐related genes directly, and it was always cross‐talk with other pathway to suppress FAO indirectly. It should be further studied if HIF1 could involve cross‐talk with more pathways to suppress FAO.
\nDe novo fatty acid synthesis begins with acetyl coenzyme A (Ac‐CoA). Ac‐CoA is primarily generated from glucose through tri‐carboxylic acid (TCA) cycle in the mitochondrion, the citrate shuttle and ATP citrate lyase in the cytosol. Under hypoxic condition, cells converted glucose to lactate and the TCA cycle is largely disconnected from glycolysis [70, 115–117], thereby directing glucose carbon away from fatty acid synthesis. Recently, several groups had found that hypoxic tumor cells maintain proliferation by running the TCA cycle in reverse [70, 115–117]. In these cells, the source of carbon for Ac‐CoA and fatty acid switched from glucose to glutamine. This hypoxic flux from glutamine to fatty acid was mediated by the reductive carboxylation of glutamine‐derived α‐ketoglutarate.
\nThe reductive carboxylation of glutamine was part of the metabolic reprogramming associated with HIF1. Glutamine‐derived α‐ketoglutarate is reductively carboxylated by the cytosolic isocitrate dehydrogenase 1 (IDH1) [70, 115] and the mitochondrial isocitrate dehydrogenase 2 (IDH2) to form isocitrate [70, 115, 116], which could then be isomerized to citrate. The combined action of IDH1 and IDH2 was necessary and sufficient to affect the reverse TCA flux [115]. Citrate was converted into Ac‐CoA by ATP citrate lyase in the cytosol. Renal cell lines deficient in the VHL preferentially used reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels [70]. Constitutive activation of HIF1 recapitulated the preferential reductive metabolism of glutamine‐derived α‐ketoglutarate even in normoxic condition [116]. This regulation by HIF1 of the reverse TCA cycle occurred partly through HIF1‐inducing PDK1. Knocking down PDK1 suppressed reductive carboxylation [70, 118]. However, more details should be studied about the role of HIF1 in TCA cycle reverse.
\nThe first step of fatty acid synthesis is catalyzed by AcCoA carboxylase (ACC) which converts Ac‐CoA to malonyl‐CoA. Then fatty‐acid synthase (FASN) catalyzes acetyl‐CoA and malonyl‐CoA to palmitate. Further elongation and de‐saturation of newly synthesized fatty acid takes place at the cytoplasmic face of the endoplasmic reticulum membrane. It had been reported that hypoxia regulated FASN expression [78, 119, 120]. However, different conclusions on hypoxia regulation of FASN had been reported. One group using human breast cancer cell lines found that FASN was significantly up‐regulated by hypoxia via activation of the Akt and HIF1 followed by the induction of the SREBP1 gene [119]. Another group, using several cell lines other than breast cancer cell lines, found that hypoxia suppressed FASN expression through HIF1‐DEC1 and/or DEC2‐SREBP1 axis. They found that HIF1 repressed the SREBP1 gene by inducing DEC1 and DEC2, and further repressing FASN expression [78]. These results might indicate that HIF1 regulated FASN in a cell‐type specific manner. In addition, it had been reported that hypoxia could induce the expression of SCD1 which introduces a double bond in the Δ9 position of palmitic acid and stearic acid to produce mono‐unsaturated fatty acid [42, 121]. It is unknown if HIF1 is involved in hypoxic‐induced SCD1.
\nTaken together, the role of HIF1 in de novo fatty acid synthesis may depend on different models and conditions, and more researches should be done in the direction.
\nCholesterol is an essential structural component of membrane. It modulates membrane permeability and fluidity and also forms microdomains named lipid rafts that integrate the activation of some signal transduction pathways [14]. Intermediates generated by the cholesterol biosynthesis pathway were required for the posttranslational modification of small GTPases, such as the farnesylation of Ras and the geranyl‐geranylation of Rho [15]. Finally, cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acids, and vitamin D.
\nCellular cholesterol level can be modulated by three processes: cholesterol uptake, synthesis, and efflux [122]. In the preceding paragraph, we had discussed the role of HIF1 in LDL and VLDL uptake that are main source of extracellular cholesterol. Here, we discuss the cholesterol synthesis and efflux. Cholesterol biosynthesis begins with the condensation of AcCoA with acetoacetyl‐CoA to form 3‐hydroxy‐3‐methylglutaryl (HMG)‐CoA. Then HMG‐CoA reductase (HMGCR) reduces of HMG‐CoA to mevalonate. Early research found that Hypoxia also suppressed cholesterol synthesis in cultured rabbit skin fibroblasts [123]. However, recently research indicated that hypoxia increased sterol synthesis depending on HIF1\'s activity [23, 124]. In hypoxic macrophages, the increase of intracellular cholesterol content was correlated with elevated HMGCR\'s activity and mRNA levels [23]. In HepG2 cells, HIF1α accumulation was able to increase the level and activity of HMGCR by stimulating its transcription [124]. But it was unclear if HIF1 regulated HMGCR directly.
\nHypoxia suppressed the efflux of cholesterol, and this efflux was substantially reversed in vitro by reducing the expression of HIF1 [23, 123]. ATP‐binding cassette transporter A1 (ABCA1) plays a major role in cholesterol efflux. Hypoxia severely reduced ABCA1‐mediated cholesterol efflux, which could be explained by subcellular redistribution of ABCA1 protein under acute hypoxia and decreased protein level under prolonged hypoxia [23]. One group reported that HIF1 could repress the transcription of ABCA1 directly [79]. Hypoxia, partly mediated by HIF1α, increased intracellular cholesterol content due to the induction of cholesterol synthesis and the suppression of cholesterol efflux [23]. In addition, accumulation of cholesterol in hypoxic cells was in esterified form [23, 100]. At 2% O2 tension, twice the total cholesteryl ester was observed compared with that at 21% O2. At the same time, no significant difference was found in the concentration of cellular‐free cholesterol [100]. Accumulation of cholesteryl ester in hypoxic cells might depend on the increased activity of AcCoA:cholesterol acyltransferases (ACATs) [123], which are important enzymes for the esterification of cholesterol. Therefore, more studies should be done to define the role of HIF1 involving the cholesterol metabolism in detail.
\nTAG is formed by the addition of three molecules of fatty acid to glycerol. There are two major pathways for TAG biosynthesis in mammalian cell: the glycerol phosphate pathway and the mono‐acylglycerol (MG) pathway. In the glycerol phosphate pathway, two molecules of fatty acyl‐CoA are esterified to glycerol‐3‐phosphate to yield 1,2‐diacylglycerol (DAG) phosphate (commonly identified as phosphatidic acid). The phosphate is then removed to yield 1,2‐diacylglycerol, which is followed by addition of the third fatty acid to form TAG. TAG accumulation under hypoxia could be mediated by HIF1‐inducing Lipin1 [20], a phosphatidate phosphatase isoform that catalyzes the penultimate step in TAG biosynthesis, the removal of phosphate from diacylglycerol phosphate to yield DAG. It also had been reported that hypoxia produced a marked intracellular accumulation of diacylglycerol in different cell types [125]. DAG may also serve a feedback role regulating HIF1\'s activity [125]. In a mouse model of pathological hypertrophy, HIF1α promoted TAG accumulation in cardiomyocytes via the regulation of PPARγ expression. PPARγ was the principal mediator of TAG anabolism through its transcriptional regulation glycerol‐3‐phosphate generation (via GPD1), and downstream esterification processes (via GPAT) [26].
\nPhospholipids are indispensable for cell growth. Phospholipids synthesis and TAG synthesis share similar steps. DAG is a precursor for phosphatidylcholine and phosphatidylethanolamine. Phosphatidic acid utilizes cytidine triphosphate (CTP) as an energy source to produce a CDP‐DAG intermediate followed by conversion to phosphatidylcholine. It had been reported that the intracellular level of phosphatidic acid (PA) and DAG rose in response to hypoxia [125, 126]. However, PA accumulation in response to hypoxia was both HIF1 and VHL‐independent [127]. Choline kinase α (ChKα) catalyzes the phosphorylation of choline, the first step of phosphatidylcholine synthesis. In cancer cells, one group had shown that hypoxia increased ChKα expression and this was driven by HIF1 [80]. Conversely, another group had shown that choline kinase activity and choline phosphorylation were decreased, that might be mediated via HIF1α binding to the promoter of ChKα gene [81]. Thus, further studies should be done to address the role of HIF1 in phospholipids metabolism.
\n\nLipid droplet, also named lipid body, has been largely associated with neutral lipid storage and transport in cells [106]. The internal core of the LD is rich in neutral lipids, predominantly TAGs or cholesteryl esters, that are surrounded by an outer monolayer of phospholipids and associated proteins [128]. LD was considered to be highly regulated, dynamic and functionally active organelle [106]. Proteins on the surface of lipid droplets are crucial to the droplet structure and dynamics. Currently, the complete protein composition of LD has not been defined. The best characterized LD’ proteins are the perilipin/ADRP/TIP47 (PAT) domain family. Apart from the PAT domain proteins, there are other lipid droplets associated proteins which involve the catabolism of lipids, vesicular transport, eicosanoid‐forming enzymes, protein kinases, etc. [106]. Hypoxia increased LD number and size [42, 129]. Several LD‐associated proteins were induced by HIF1 and might also involve HIF1‐induced LD biogenesis and lipid signaling (Figure 3).
\n\nAdipose differentiation‐related protein (ADRP), a PAT domain protein, is a structural component of LD and had been reported by several groups to be inducible by HIF1 [42, 82–84]. Lipid accumulation was associated with high expression level of ADRP in solid tumors [68, 130], especially in clear cell lesions [131]. During the process of carcinogenesis, the ADRP expression was increased during early tumorigenesis and was associated with the proliferation rate [68]. The expression of ADRP was also correlated with atherosclerosis [132]. In mouse macrophages in vitro, ADRP expression facilitated foam cell formation induced by modified lipoproteins [132]. In apolipoprotein E‐deficient mice, ADRP inactivation reduced the number of LD in foam cells in atherosclerotic lesions [132]. Under hypoxia, knockdown of ADRP in U87 and T98G or in MCF‐7 and MDA‐MB‐231 cells significantly decreased the formation of LD, and resulted in decreased fatty acid uptake [21]. It indicated that ADRP promoted LD formation mainly through increasing FA uptake under hypoxic condition. It had been reported that ADRP can also stimulate LCFA uptake [133]. While another research reported that ADRP did not involve LDL‐ and VLDL‐induced LD formation under hypoxia [84].
\nA hypothetical representation of molecular mechanism involving hypoxia‐induced lipid droplet biogenesis and function. HIF1‐induced structural proteins of the LD, such as ADRP, HIG2, combine with HIF1‐increased lipids to form the LD. Enzymes involving eicosanoid production are also induced by HIF1, and are recruited to the LD. These proteins can increase lipid signaling that can involve many aspects of biology, such as HIF1α\'s stability, angiogenesis, inflammation, cell proliferation and survival.
Hypoxia‐inducible protein 2 (HIG2), a newly identified protein associated with LD, was up‐regulated by hypoxia and was a direct and specific target gene of HIF1 [85]. Overexpression of HIG2 under normoxic condition was sufficient to increase LD in HeLa cells. HIG2‐driven LD might contribute to an inflammatory response. Overexpression of HIG2 stimulated cytokine expression of vascular endothelial growth factor‐A (VEGFA), macrophage migration inhibitory factor (MIF), and interleukin‐6 (IL‐6). Increasing expression of HIG2 was also detected under several conditions of pathological lipid accumulation, such as atherosclerotic arteries and fatty liver disease [85]. We had mentioned that CAV1 was a target of HIF1. CAV1 could distribute to LD under several conditions [134–137] and the association with LD was reversible [134]. However, It is unknown if hypoxia can redistribute CAV1 to LD and CAV1 involves LD biogenesis under hypoxia.
\nEicosanoids are signaling molecules made by oxidation of 20‐carbon fatty acids, mainly from arachidonic acid. Cyclooxygenases and Lipoxygenases are two families of enzymes catalyzing fatty acid oxygenation to produce the eicosanoids. There are multiple subfamilies of eicosanoids, including prostaglandins, prostacyclins, thromboxanes, lipoxins, and leukotrienes. Prostaglandins, such as PGI2 and PGE2, are synthesized via cyclooxygenase (COX) by oxidation of arachidonic acid. PGE2 is synthesized in three steps catalyzed by phospholipase (PL) A2, COX, and terminal prostaglandin E synthase (PTGES), where each catalytic activity is represented by multiple enzymes and/or isoenzymes. It had been reported that hypoxia could increase prostaglandins (PGI2 and PGE2) synthesis [138]. Hypoxia‐induced synthesis of PGE2 was accompanied by up‐regulation of COX2, which is a direct target gene of HIF1 [86]. Several studies had indicated that LD was reservoirs of COX2 and sites of PGE2 synthesis [66, 139, 140]. PTGES1 could also be regulated by HIF1 directly [87, 88]; however, it is unknown if PTGES1 localizes to hypoxia‐induced LD.
\nLipoxygenases are a family of nonheme iron‐containing enzymes which dioxygenate polyunsaturated fatty acid to hydroperoxyl metabolite, and mainly include 5‐lipoxygenase (5‐LO), 12‐lipoxygenase (12‐LO), and 15‐lipoxygenase (15‐LO). 5‐LO and 15‐LO were shown by immuno‐cytochemistry, immuno‐fluorescence, ultrastructural postembedding immuno‐gold EM and/or western blotting from subcellular fractions to localize within lipid droplets stimulated in vitro [141–144]. Increasing level of 5‐LO was detected in lung tissue of rodent model of hypoxia‐induced pulmonary hypertension [145]. Hypoxia increased 12‐LO in rat lung and in in vitro cultured rat pulmonary artery smooth muscle cell (PASMC) and may contribute to the production of 12(S)‐hydroxyeicosatetraenoic acid (12(S)‐HETE) [146]. Increasing 12(S)‐HETE had also been demonstrated in hypoxic macrophage cells [147]. Under hypoxia, increased levels of 15‐LO had been demonstrated by different groups [147, 148] and its product, 15‐hydroperoxyeicosatetraenoic acid (15‐HETE), was up‐regulated [147]. Up‐regulation of 15‐LO/15‐HETE in response to hypoxia might be partially mediated by HIF1α [149]. In addition, HIF1α was shown to be regulated by 15‐HETE in a positive feedback manner [149]. However, it is unknown if lipoxygenases are regulated by HIF1 directly.
\nHIF1 plays an important role in lipid metabolism and a number of studies support the findings that HIF1 promotes lipid accumulation. Nevertheless, many questions remain. HIF1, as a master transcriptional factor, may target many genes directly or indirectly involved in lipid metabolism. HIF1 plays a pivotal role in glucose metabolism. Inhibition of GULT3, an HIF1 target gene, could significantly reduce both glucose uptake and hypoxia‐induced de novo lipid synthesis in human monocyte‐derived macrophages [150]. PGAM1, induced by hypoxia [151], catalyzes the reversible reaction of 3‐phosphoglycerate (3‐PGA) to 2‐phosphoglycerate (2‐PGA) in the glycolytic pathway. Inhibition of PGAM1 led to significantly decreased glycolysis and de novo lipid synthesis in cancer cells [152]. Thus, it is possible that glucose metabolism might couple with lipid metabolism under hypoxia. The source of carbon for fatty acid switched from glucose to glutamine under hypoxia [70]. The question thus arises. Does HIF1 induce lipid accumulation through targeting genes involving glucose metabolism, and how does glucose metabolism affect lipid metabolism under hypoxia?
\nHIF1 could interact with other pathways to regulate lipid metabolism besides PPARα, PPARγ, PPARδ, PGC1α, and SREBP1. There might be a pivotal role for mTOR in controlling lipid homeostasis in many settings, both physiological and pathological [153]. AMPK is a cellular energy sensor that normalizes lipid, glucose, and energy imbalances [154]. Inhibition of cMYC was accompanied by accumulation of intracellular LD in tumor cells as a direct consequence of mitochondrial dysfunction [155]. Recently, p53 had also been shown to regulate lipid metabolism [156]. The role of HIF1 in these pathways and the molecular mechanism will require further investigation.
\nLipid accumulation in diseases, including obesity, atherosclerosis, ALD, heart failure disease and cancer, had been associated with HIF1\'s activity. There may be additional pathologies with lipid metabolism disorder associated with HIF1. HIF1 is an attractive target candidate for therapeutic intervention in diseases with disorder of lipid metabolism including cancer. Its involvement in the etiology of a number of diseases and its interaction with a number of regulatory genes make it an important area for further study.
\nThis review is supported by a National Natural Science Foundation of China (Grant No. 31301076 to G. S; Grant No. 81401961 to X. L.), We thank Gerard Moskowitz, Ph. D. (Washington University in St. Louis, St. Louis, MO) for critical reading of the manuscript. We sincerely apologize to the colleagues whose works are not covered in this review due to limitations of time and space.
\nSensing and responding to environmental stimuli is necessary for bacteria to adjust the expression of related genes and adapt to changing habitats. The two-component systems (TCSs) are the most widespread regulation system in bacteria [8]. The TCS is mainly composed of two proteins, histidine kinase (HK) and their cognate response regulator (RR) (Figure 1). Histidine kinase is a membrane protein that can sense extracellular signals and autophosphorylate its histidine. The phosphorylated HK can transfer the phosphoryl group to its cognate RR protein leading to the phosphorylation of the RR protein at the aspartate residue (Asp) and the activation of RR protein. The activated RR protein is able to change its conformation by dimerization or multimerization and regulates the expression of its target genes. In general, the RR protein can regulate gene transcription by binding to specific sequences in the promoter region of related genes located upstream of the RNA polymerase binding region.
Two-component system regulation mechanism.
Although not completely understood, the study of molecular regulation mechanisms in acidophilic bacteria has recently been progressing. In this chapter, we discuss the occurrence of the TCS in these bacteria, the regulation mechanism of sulfur and iron oxidation, and the future prospects in the TCS regulation research.
The occurrence of the TCSs in the acidophilic bacteria was compared among different species on basis of the reported TspS-TspR, RsrS-RsrR, and RegB-RegA two-component systems [7, 9, 10] (Figure 2). The sulfur oxidization (Sox) system is a critical sulfur oxidization pathway of chemotrophic sulfur-oxidizing bacteria, and the regulation of the Sox system in
Distribution of two-component system in acidophilic bacteria. The identities of corresponding protein were indicated by the percentage values with the first line of each part set as 100%. Accession numbers (GenBank) for proteins in Sox pathway are as follows,
The S4I pathway is also an important thiosulfate oxidization pathway composed of tetrathionate hydrolase (TetH) and thiosulfate: quinone oxidoreductase (DoxDA), and its regulation by the RsrS-RsrR system was reported [9, 11]. However, a similar distribution of this gene cluster was only found in
The RegB-RegA is a well-studied global redox responding regulatory system in
Hence, the TCSs are widespread in the sulfur and iron oxidization bacteria, while different distributions are revealed by bioinformatics analysis and different regulation mechanism maybe adapted, which deserves further studies.
Gene transcription is a fundamental process in bacteria, which is carried out by multi-subunit RNA polymerase (RNAP). σ factors determine transcription specificity by recognizing specific promoter sequences. Bacterial σ factors can be divided into two distinct classes: σ70 and σ54 [14]. σ70 recognizes the consensus −10 and − 35 regions and recruits RNAP to a specific promoter region to initiate gene transcription [15]. σ70 controls transcription of most housekeeping genes, whereas σ54 regulates the genes involved in nitrogen assimilation [16], phage shock response [17], infection [18], and other cellular stresses [19, 20]. σ54 recognizes distinct sequences in the −12 (GC) and − 24 (GG) regions of the promoter. The requirement of the bacterial enhancer binding proteins (bEBPs) is a remarkable feature of σ54-dependent transcription initiation [20]. Accordingly, two kinds of transcription regulation were reported in acidophilic bacteria (Figure 3).
Different TCS regulation mechanisms between the sox system and the S4I pathway. Sox system and the S4I pathway are important sulfur oxidation system in
The
The RR protein of TCS can function as the activator of σ54-dependent transcription initiation, which converts the closed RNAP-σ54 holoenzyme complex to open state to initiate transcription. σ54 -dependent RR proteins have been reported in several bacteria [21, 22, 23]. It was reported that the two-component system TspS-TspR could regulate the sulfur oxidization (Sox) system in
When
Moreover, other regulatory proteins may be involved in the regulation of these genes. The transcription factor Fur was proven to control the transcription of
Based on the reported results, the regulation model for RegBA two-component system is portrayed in Figure 4. When Fe (II) is used as the electro donor, RegB is able to sense the low potential state and activate through autophosphorylation. It then activates the RegA protein by transferring the phosphoryl group to the conserved Asp residue of RegA. Phosphorylated RegA protein multimerizes and binds to the promoter region of the target genes, which may activate iron oxidation genes by repressing the binding of other repressor proteins such as Fur for
Regulation of sulfur and ferrous iron oxidation by the TCS system. The regulation in
Two component systems possess critical roles in the regulation of sulfur and iron oxidation in acidophilic bacteria. In the sulfur oxidizing species
This work was supported by grants from the National Natural Science Foundation of China (31900116), the Scientific and Technological Projects of Henan Province (202102310395), the Natural Science Foundation of Shandong Province (6622320549) and the Medical Science and Technology Projects of Henan Province (LHGJ20190955).
The authors declare no conflict of interests.
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. 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:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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The main pollutants can be poisons, chemical compounds, toxic gases, and bacterial toxins. These can be found in different places and their effects depend on the dose and exposure time. Furthermore, foodborne diseases (FBDs) can cause disability; these diseases can be caused by toxins produced by bacteria or other toxic substances in the food, which can cause severe diarrhea, toxic shock syndrome, debilitating infections such as meningitis and even death. FBDs are transmitted through food contaminated with pathogenic microorganisms that have multiple factors of virulence, which gives them the ability to cause an infection; some bacterial genres can produce toxins directly in the food, but other genres can produce them once they have colonized the intestine. Among the pathogens involved in FBDs that are also considered to be toxigenic are Salmonella spp., Vibrio parahaemolyticus, Vibrio cholerae, Staphylococcus aureus, Clostridium botulinum, Clostridium perfringens, Bacillus cereus, Listeria monocytogenes. Foodborne diseases can be prevented and acute diarrhea syndromes, fever and even death from dehydration can be avoided, especially in children under the age of 5 and in immunocompromised people.",book:{id:"5873",slug:"poisoning-from-specific-toxic-agents-to-novel-rapid-and-simplified-techniques-for-analysis",title:"Poisoning",fullTitle:"Poisoning - From Specific Toxic Agents to Novel Rapid and Simplified Techniques for Analysis"},signatures:"Cecilia Hernández-Cortez, Ingrid Palma-Martínez, Luis Uriel\nGonzalez-Avila, Andrea Guerrero-Mandujano, Raúl Colmenero Solís\nand Graciela Castro-Escarpulli",authors:[{id:"204160",title:"Prof.",name:"Graciela",middleName:null,surname:"Castro-Escarpulli",slug:"graciela-castro-escarpulli",fullName:"Graciela Castro-Escarpulli"},{id:"204162",title:"Dr.",name:"Cecilia",middleName:null,surname:"Hernández-Cortez",slug:"cecilia-hernandez-cortez",fullName:"Cecilia Hernández-Cortez"},{id:"204163",title:"MSc.",name:"Ingrid",middleName:null,surname:"Palma-Martinez",slug:"ingrid-palma-martinez",fullName:"Ingrid Palma-Martinez"},{id:"204164",title:"MSc.",name:"Luis Uriel",middleName:null,surname:"González-Avila",slug:"luis-uriel-gonzalez-avila",fullName:"Luis Uriel González-Avila"},{id:"204165",title:"MSc.",name:"Andrea",middleName:null,surname:"Guerrero-Mandujano",slug:"andrea-guerrero-mandujano",fullName:"Andrea Guerrero-Mandujano"}]},{id:"51450",doi:"10.5772/63888",title:"ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring",slug:"ecmo-biocompatibility-surface-coatings-anticoagulation-and-coagulation-monitoring",totalDownloads:4397,totalCrossrefCites:9,totalDimensionsCites:17,abstract:"The interaction between the patient and the ECMO (extracorporeal membrane oxygenation) circuit initiates a significant coagulation and inflammatory response due to the large surface area of foreign material contained within the circuit. This response can be blunted with the appropriate mix of biocompatible materials and anticoagulation therapy. The use of anticoagulants, in turn, requires appropriate laboratory testing to determine whether the patient is appropriately anticoagulated. Physicians must balance the risks of bleeding with the risks of thrombosis; the proper interpretation of these tests is often shrouded in mystery. It is the purpose of this chapter to help demystify the coagulation system, anticoagulants, biocompatible surfaces, and coagulation testing so that ECMO practitioners can make informed decisions about their patients and to spur coordinated efforts for future research to improve our understanding of these complex processes.",book:{id:"5202",slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"Timothy M. Maul, M Patricia Massicotte and Peter D. Wearden",authors:[{id:"182691",title:"Dr.",name:"Timothy",middleName:"Michael",surname:"Maul",slug:"timothy-maul",fullName:"Timothy Maul"},{id:"187110",title:"Dr.",name:"Peter",middleName:null,surname:"Wearden",slug:"peter-wearden",fullName:"Peter Wearden"},{id:"187112",title:"Dr.",name:"Patti",middleName:null,surname:"Massicotte",slug:"patti-massicotte",fullName:"Patti Massicotte"}]},{id:"56530",doi:"10.5772/intechopen.69955",title:"Poisoning by Anticoagulant Rodenticides in Humans and Animals: Causes and Consequences",slug:"poisoning-by-anticoagulant-rodenticides-in-humans-and-animals-causes-and-consequences",totalDownloads:1823,totalCrossrefCites:9,totalDimensionsCites:15,abstract:"Anticoagulant rodenticides (ARs) are a keystone of the management of rodent populations in the world. The widespread use of these molecules raises questions on exposure and intoxication risks, which define the safety of these products. Exposures and intoxications can affect humans, domestic animals and wildlife. Consequences are different for each group, from the simple issue of intoxication in humans to public health concern if farm animals are exposed. After a rapid presentation of the mechanism of action and the use of anticoagulant rodenticides, this chapter assesses the prominence of poisoning by anticoagulant rodenticides in humans, domestic animals and wildlife.",book:{id:"5873",slug:"poisoning-from-specific-toxic-agents-to-novel-rapid-and-simplified-techniques-for-analysis",title:"Poisoning",fullTitle:"Poisoning - From Specific Toxic Agents to Novel Rapid and Simplified Techniques for Analysis"},signatures:"Sébastien Lefebvre, Isabelle Fourel, Stéphane Queffélec, Dominique\nVodovar, Bruno Mégarbane, Etienne Benoit, Virginie Siguret and\nVirginie Lattard",authors:[{id:"180156",title:"Dr.",name:"Virginie",middleName:null,surname:"Lattard",slug:"virginie-lattard",fullName:"Virginie Lattard"},{id:"185579",title:"Dr.",name:"Sébastien",middleName:null,surname:"Lefebvre",slug:"sebastien-lefebvre",fullName:"Sébastien Lefebvre"},{id:"185580",title:"Prof.",name:"Etienne",middleName:null,surname:"Benoit",slug:"etienne-benoit",fullName:"Etienne Benoit"},{id:"209023",title:"Dr.",name:"Isabelle",middleName:null,surname:"Fourel",slug:"isabelle-fourel",fullName:"Isabelle Fourel"},{id:"209031",title:"Mr.",name:"Stéphane",middleName:null,surname:"Queffélec",slug:"stephane-queffelec",fullName:"Stéphane Queffélec"},{id:"209032",title:"Dr.",name:"Bruno",middleName:null,surname:"Megarbane",slug:"bruno-megarbane",fullName:"Bruno Megarbane"},{id:"209033",title:"Dr.",name:"Dominique",middleName:null,surname:"Vodovar",slug:"dominique-vodovar",fullName:"Dominique Vodovar"},{id:"209034",title:"Prof.",name:"Virginie",middleName:null,surname:"Siguret",slug:"virginie-siguret",fullName:"Virginie Siguret"}]},{id:"39638",doi:"10.5772/51484",title:"The History of Sepsis from Ancient Egypt to the XIX Century",slug:"the-history-of-sepsis-from-ancient-egypt-to-the-xix-century",totalDownloads:10503,totalCrossrefCites:5,totalDimensionsCites:15,abstract:null,book:{id:"2583",slug:"sepsis-an-ongoing-and-significant-challenge",title:"Sepsis",fullTitle:"Sepsis - An Ongoing and Significant Challenge"},signatures:"Johan Sebastián Hernández Botero and María Cristina Florián Pérez",authors:[{id:"141171",title:"Dr.",name:"Johan",middleName:"Sebastian",surname:"Hernandez Botero",slug:"johan-hernandez-botero",fullName:"Johan Hernandez Botero"},{id:"141520",title:"Dr.",name:"Maria Cristina",middleName:null,surname:"Florian Perez",slug:"maria-cristina-florian-perez",fullName:"Maria Cristina Florian Perez"}]}],mostDownloadedChaptersLast30Days:[{id:"56521",title:"Food Poisoning Caused by Bacteria (Food Toxins)",slug:"food-poisoning-caused-by-bacteria-food-toxins-",totalDownloads:5827,totalCrossrefCites:9,totalDimensionsCites:20,abstract:"In the environment, there are polluting substances that can cause adverse reactions in human beings when entering the body through different ways (ingestion, inhalation, injection, or absorption). The main pollutants can be poisons, chemical compounds, toxic gases, and bacterial toxins. These can be found in different places and their effects depend on the dose and exposure time. Furthermore, foodborne diseases (FBDs) can cause disability; these diseases can be caused by toxins produced by bacteria or other toxic substances in the food, which can cause severe diarrhea, toxic shock syndrome, debilitating infections such as meningitis and even death. FBDs are transmitted through food contaminated with pathogenic microorganisms that have multiple factors of virulence, which gives them the ability to cause an infection; some bacterial genres can produce toxins directly in the food, but other genres can produce them once they have colonized the intestine. Among the pathogens involved in FBDs that are also considered to be toxigenic are Salmonella spp., Vibrio parahaemolyticus, Vibrio cholerae, Staphylococcus aureus, Clostridium botulinum, Clostridium perfringens, Bacillus cereus, Listeria monocytogenes. Foodborne diseases can be prevented and acute diarrhea syndromes, fever and even death from dehydration can be avoided, especially in children under the age of 5 and in immunocompromised people.",book:{id:"5873",slug:"poisoning-from-specific-toxic-agents-to-novel-rapid-and-simplified-techniques-for-analysis",title:"Poisoning",fullTitle:"Poisoning - From Specific Toxic Agents to Novel Rapid and Simplified Techniques for Analysis"},signatures:"Cecilia Hernández-Cortez, Ingrid Palma-Martínez, Luis Uriel\nGonzalez-Avila, Andrea Guerrero-Mandujano, Raúl Colmenero Solís\nand Graciela Castro-Escarpulli",authors:[{id:"204160",title:"Prof.",name:"Graciela",middleName:null,surname:"Castro-Escarpulli",slug:"graciela-castro-escarpulli",fullName:"Graciela Castro-Escarpulli"},{id:"204162",title:"Dr.",name:"Cecilia",middleName:null,surname:"Hernández-Cortez",slug:"cecilia-hernandez-cortez",fullName:"Cecilia Hernández-Cortez"},{id:"204163",title:"MSc.",name:"Ingrid",middleName:null,surname:"Palma-Martinez",slug:"ingrid-palma-martinez",fullName:"Ingrid Palma-Martinez"},{id:"204164",title:"MSc.",name:"Luis Uriel",middleName:null,surname:"González-Avila",slug:"luis-uriel-gonzalez-avila",fullName:"Luis Uriel González-Avila"},{id:"204165",title:"MSc.",name:"Andrea",middleName:null,surname:"Guerrero-Mandujano",slug:"andrea-guerrero-mandujano",fullName:"Andrea Guerrero-Mandujano"}]},{id:"64561",title:"Musculoskeletal Injuries: Types and Management Protocols for Emergency Care",slug:"musculoskeletal-injuries-types-and-management-protocols-for-emergency-care",totalDownloads:2430,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"These are a common type of human injuries which can result from the damage of muscular or skeletal systems (i.e., bones, muscles, tendons, ligaments, nerves, blood vessels, etc.); they usually occur due to a strenuous and/or repetitive activity and can result into variety of complaints, complications, and deformities causing a big burden on the financial and health system in all societies. They are among the largest category of work-related injuries and are responsible for almost 30% of all worker’s compensation costs worldwide. Injuries to the musculoskeletal system occur in 85% of patients who sustain blunt trauma; they often appear dramatic, but rarely cause an immediate life-threatening situation, although these injuries must be assessed and managed accurately so life or limb are not jeopardized. The doctor must be familiar with the anatomy and the injury site to protect his patients from further disability and prevent complications. Major musculoskeletal trauma such as crushed injuries that can cause release of myoglobin resulting in renal tubular injury (acute kidney injury), or can be associated with internal torso injuries like acute compartment syndrome. soft tissue and skeletal system traumas may not be initially recognized, so continued reassessment and evaluation are necessary to identify all injuries.",book:{id:"6616",slug:"essentials-of-accident-and-emergency-medicine",title:"Essentials of Accident and Emergency Medicine",fullTitle:"Essentials of Accident and Emergency Medicine"},signatures:"Ahmad Subhy Alsheikhly and Mazin Subhy Alsheikhly",authors:[{id:"144628",title:"Prof.",name:"Ahmad Subhy",middleName:"Humadi",surname:"Alsheikhly",slug:"ahmad-subhy-alsheikhly",fullName:"Ahmad Subhy Alsheikhly"}]},{id:"59641",title:"Problem of Burns in Children: Opportunities for Health Improvement",slug:"problem-of-burns-in-children-opportunities-for-health-improvement",totalDownloads:1386,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Burns are one of the most devastating types of trauma in medicine. Children under 5 years of age are a high-risk group to burns. The most common type is thermal burn caused by hot fluids (scald). Most childhood burns occur at home under parental supervision. These are preventable injuries. The chapter presents results of my studies about risk factors of burns in children and possibilities of health improvement. Simple changes in children’s environment and increasing awareness of caregivers can lead to a decrease in the number of this type of injuries. Moreover, the first aid given to burnt children soon after the injury usually is not adequate (no cooling thermal burns and no analgesia). Health improvement can be obtained by reducing the number of burns, the correct first aid given after the injury, and the organization of specialized health-care centers and rehabilitation services for victims of burns.",book:{id:"6616",slug:"essentials-of-accident-and-emergency-medicine",title:"Essentials of Accident and Emergency Medicine",fullTitle:"Essentials of Accident and Emergency Medicine"},signatures:"Agata Maria Kawalec",authors:null},{id:"51795",title:"ECMO Cannulation Techniques",slug:"ecmo-cannulation-techniques",totalDownloads:4289,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"An extracorporeal membrane oxygenation (ECMO) circuit consists of a pump and a membrane oxygenator. This circuit can interface with the human body in a variety of cannulation strategies to provide different forms and levels of support. These various support techniques can be divided into two broad categories: those designed to support the body’s respiratory functions (lungs) and those designed to support the body’s blood circulation (heart). In this chapter we discuss various cannulation techniques used.",book:{id:"5202",slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"Chand Ramaiah and Ashok Babu",authors:[{id:"183646",title:"Dr.",name:"Chand",middleName:null,surname:"Ramaiah",slug:"chand-ramaiah",fullName:"Chand Ramaiah"},{id:"189073",title:"Dr.",name:"Ashok",middleName:null,surname:"Babu",slug:"ashok-babu",fullName:"Ashok Babu"}]},{id:"27955",title:"Transfusion-Associated Bacterial Sepsis",slug:"transfusion-associated-sepsis",totalDownloads:8258,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"802",slug:"severe-sepsis-and-septic-shock-understanding-a-serious-killer",title:"Severe Sepsis and Septic Shock",fullTitle:"Severe Sepsis and Septic Shock - Understanding a Serious Killer"},signatures:"Jolanta Korsak",authors:[{id:"72828",title:"Prof.",name:"Jolanta",middleName:null,surname:"Korsak",slug:"jolanta-korsak",fullName:"Jolanta Korsak"}]}],onlineFirstChaptersFilter:{topicId:"177",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:86,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:96,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:283,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:138,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:128,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:100,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:8,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:9,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"13633",title:"Prof.",name:"Abdelhamid",middleName:null,surname:"Mellouk",slug:"abdelhamid-mellouk",fullName:"Abdelhamid Mellouk",profilePictureURL:"https://mts.intechopen.com/storage/users/13633/images/1567_n.jpg",institutionString:null,institution:{name:"Paris 12 Val de Marne University",institutionURL:null,country:{name:"France"}}},{id:"109268",title:"Dr.",name:"Ali",middleName:null,surname:"Al-Ataby",slug:"ali-al-ataby",fullName:"Ali Al-Ataby",profilePictureURL:"https://mts.intechopen.com/storage/users/109268/images/7410_n.jpg",institutionString:null,institution:{name:"University of Liverpool",institutionURL:null,country:{name:"United Kingdom"}}},{id:"3807",title:"Dr.",name:"Carmelo",middleName:"Jose Albanez",surname:"Bastos-Filho",slug:"carmelo-bastos-filho",fullName:"Carmelo Bastos-Filho",profilePictureURL:"https://mts.intechopen.com/storage/users/3807/images/624_n.jpg",institutionString:null,institution:{name:"Universidade de Pernambuco",institutionURL:null,country:{name:"Brazil"}}},{id:"38850",title:"Dr.",name:"Efren",middleName:null,surname:"Gorrostieta Hurtado",slug:"efren-gorrostieta-hurtado",fullName:"Efren Gorrostieta Hurtado",profilePictureURL:"https://mts.intechopen.com/storage/users/38850/images/system/38850.jpg",institutionString:null,institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},{id:"239041",title:"Prof.",name:"Yang",middleName:null,surname:"Yi",slug:"yang-yi",fullName:"Yang Yi",profilePictureURL:"https://mts.intechopen.com/storage/users/239041/images/system/239041.jpeg",institutionString:"Virginia Tech",institution:{name:"Virginia Tech",institutionURL:null,country:{name:"United States of America"}}}]},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"13818",title:"Dr.",name:"Asim",middleName:null,surname:"Bhatti",slug:"asim-bhatti",fullName:"Asim Bhatti",profilePictureURL:"https://mts.intechopen.com/storage/users/13818/images/system/13818.jpg",institutionString:null,institution:{name:"Deakin University",institutionURL:null,country:{name:"Australia"}}},{id:"151889",title:"Dr.",name:"Joao Luis Garcia",middleName:null,surname:"Rosa",slug:"joao-luis-garcia-rosa",fullName:"Joao Luis Garcia Rosa",profilePictureURL:"https://mts.intechopen.com/storage/users/151889/images/4861_n.jpg",institutionString:null,institution:{name:"University of Sao Paulo",institutionURL:null,country:{name:"Brazil"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",institutionURL:null,country:{name:"Turkey"}}}]},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"1177",title:"Prof.",name:"Antonio",middleName:"J. 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Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). 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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:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"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:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}},{id:"351158",title:"Prof.",name:"David W.",middleName:null,surname:"Anderson",slug:"david-w.-anderson",fullName:"David W. Anderson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",country:{name:"Canada"}}},{id:"351159",title:"BSc.",name:"Kalum J.",middleName:null,surname:"Ost",slug:"kalum-j.-ost",fullName:"Kalum J. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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