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\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
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\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
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\n\nBiomedical Engineering, ISSN 2631-5343
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\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
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Plants rich in essential oils represent a viable source of biomolecules for use in the most varied human activities, such as agricultural, cosmetic, and pharmaceutical applications. Essential oils are natural volatile fractions extracted from aromatic plants that are formed by classes of substances such as fatty acid esters, mono and sesquiterpenes, phenylpropanoids, and aldehyde alcohols, and in some cases, aliphatic hydrocarbons, among others. In this context, this book includes twelve chapters that present new information on the extraction and application of essential oils in various industrial segments. It is divided into three sections that discuss the general concepts of essential oils and techniques for their extraction, topics in food science and technology, and essential oils and their pharmacological properties in various activities and applications.",isbn:"978-1-80355-754-0",printIsbn:"978-1-80355-753-3",pdfIsbn:"978-1-80355-755-7",doi:"10.5772/intechopen.98130",price:119,priceEur:129,priceUsd:155,slug:"essential-oils-advances-in-extractions-and-biological-applications",numberOfPages:228,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"742e6cae3a35686f975edc8d7f9afa94",bookSignature:"Mozaniel Santana de Oliveira and Eloisa Helena de Aguiar Andrade",publishedDate:"June 23rd 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11332.jpg",keywords:null,numberOfDownloads:636,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfDimensionsCitations:1,numberOfTotalCitations:2,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 19th 2021",dateEndSecondStepPublish:"November 16th 2021",dateEndThirdStepPublish:"January 15th 2022",dateEndFourthStepPublish:"April 5th 2022",dateEndFifthStepPublish:"June 4th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"8 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:'A researcher with a Ph.D. degree in Food Science and Technology from the Federal University of Pará, former Academy Mentor on the Web of Science (Publons), currently a reviewer of 20 international journals, and academic editor of the journal "Evidence-based Complementary and Alternative Medicine". Dr. Santana de Oliveira co-directs doctoral and master\'s students at the Postgraduate Programs PPGBOT and BIONORTE in partnership with Dr. Eloisa Helena de Aguiar Andrade and Dr. Ely Simome Cashew Gurgel.',coeditorOneBiosketch:"A researcher in Organic Chemistry, Food Chemistry, and Botany, with over 500 publications, three books edited, 297 works indexed in WOS and SCOPUS, and 3380 total citations.\r\nDr. Andrade is an associated researcher for the Paraense Museum Emilio Goeldi and Adjunta, Teacher of the Postgraduate Programs in Chemistry, UFPA, PPG- in C. 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From 2010 to 2014, he worked on the chemistry of natural products at the Empresa Brasileira de Pesquisa Agropecuária (Embrapa), and from 2014 to 2018, he worked in the Postgraduate Program in Food Science and Technology at the Federal University of Pará, specifically with essential oils. Since 2020, he has been a researcher for the Institutional Training Program - PCI, at the institution Museu Paraense Emilio Goeldi, linked to the Ministério da Ciência, Tecnologia e Inovações of Brazil (MCTI), with studies focused on extraction, characterization chemistry, and applications of essential oils in several industrial segments, among them the food industry. Specifically, Dr. Oliveira has experience in engineering, food science and technology, pharmacology and drug discovery, medicinal chemistry, ethnopharmacology and ethnobotany, phytochemistry, methods of extraction of bioactive compounds, biotechnology of natural products, and allelopathy to find new natural herbicides to control invasive plants. He also has experience in the area of essential oil extraction using supercritical technology and conventional methods. Since 2020, he has supervised and co-supervised master’s and Ph.D. students in several graduate programs. Dr. Oliveira serves as a reviewer for thirty-one international scientific journals and is the academic editor of the journals Evidence-based Complementary and Alternative Medicine, Journal of Food Quality, Molecules, and Open Chemistry.",institutionString:"Museu Paraense Emílio Goeldi",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Museu Paraense Emílio Goeldi",institutionURL:null,country:{name:"Brazil"}}}],coeditorOne:{id:"314369",title:"Dr.",name:"Eloisa",middleName:null,surname:"Helena De Aguiar Andrade",slug:"eloisa-helena-de-aguiar-andrade",fullName:"Eloisa Helena De Aguiar Andrade",profilePictureURL:"https://mts.intechopen.com/storage/users/314369/images/system/314369.jpg",biography:"Eloisa Helena de Aguiar Andrade holds a degree in Pharmacy (1980), a qualification in Biochemistry (1982), a master\\'s degree in Chemistry of Natural Products (1992), and a Ph.D. in Chemistry (2008) from the Federal University of Pará, Brazil. For. She is currently Associate Researcher II at the Botany Coordination of the Museu Paraense Emílio Goeldi and Adjunct Professor III at the Faculty of Chemistry at the Federal University of Pará. Professor of the Graduate Programs in Chemistry, UFPA, PPG- in Biological C. - Tropical Botany, UFRA/MPEG and Graduate in Biodiversity Biotechnology - Bionorte Network. She is the coordinator of the Pole of the State of Pará, Graduate Program in Biodiversity and Biotechnology (PPG-BIONORTE/PA) of the Bionorte Network (2016-2020). Dr. Andrade is the author of more than 500 scientific contributions, including articles, event communications, book chapters, and books. 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Indeed, data in Europe show that milk production is surplus, but it is in deficit in Africa and South America [1]. The breeding programs for dairy animals have led to an increase in the quantity of milk. The reasons of this increase in milk yield include udder size, connective tissue mass, and secretory tissue. In fact, a hypertrophy of the secretory tissue of the udder is accompanied by a large milk production that can only be expressed phenotypically when the volume of the udder cistern is important to facilitate the storage of the milk produced [2, 3, 4, 5, 6, 7].
\nIn practice, because of the selection pressure exerted on the morphology of the udder, for example, cows with a high milk production must be milked at least three times a day. So, the increase in milking frequency has improved milk production in cows (15–20%, [8]). However, this practice reduces the fat matter, protein, fertility, and productive life of dairy cows [9]. It should be noted that the increase in the number of milkings per day is not accepted by farmers who are looking for farming practices to reduce the number of milkings per week and improve the quality of life on the farm [6].
\nTo avoid increasing the number of milkings per day and reducing milk losses, a strategy based on the selection of ruminants with large udder cistern to store a large quantity of milk was adopted [2, 3]. Therefore, noninvasive in vivo imaging techniques to measure udder storage capacity have been developed [10, 11, 12, 13, 14, 5].
\nIndeed, the study of the internal morphology of the udder in ruminants will know an important development soon. Scientific advances such as embryo transplantation and cloning can contribute to increased uniformity of livestock. Therefore, with this new orientation, it is interesting to take into account, in addition to the external volume of the udder, the internal size of the udder, the capacity of distension of the cells, and the kinetics of udder filling to ensure better adaptation of the udders to the number of milkings (conventional mechanical milking and robotic) and the different milk production systems (extensive, intensive) to maximize farmer’s income.
\nThe purpose of the use of morphological traits in a dairy breeding scheme is to improve the functional longevity of animals by reducing the frequency of reforms and facilitate the adaptation of animals to milking, mechanics, as well as the work of the breeder. In fact, the study of mammary morphometry in dairy animals permits identifying correlations between some morphological traits and milk production as well as the possibility of mechanical milking.
\nSeveral authors have studied the external morphological characteristics of the udder in ruminants for performance evaluation and mechanical milking skills [15, 16, 17, 18]. The importance of these morphological measurements of the cow’s udder has been accentuated by the interest in the application of the system of mechanical milking by robot [19]. In dairy cows, the large udders are usually the ones that give the most milk. Moreover, the correlations between the estimated volume of the udder and the milk production can vary from 0.60 to 0.82 depending on the breed [20]. According to the same authors, the teats must be implanted vertically, and the distance between them must never be less than 6 cm. Wide teats are associated with udder health risks and with the quality of produced milk [21]. In cattle, positive correlations have been confirmed between the distances of the teats and the teat diameter and milk yield of cows [15]. The same researchers have shown that some features of cows’ mammary morphology may be associated with a risk of higher mastitis such as low teats and wide teats, as they may increase the risk of injury and the entry of pathogens inside the udder.
\nIn ewes, the criteria of the size and shape of the udder and teats are positively correlated with milk production [21] and milk flow [22]. The presence of developed udder implies a good ability to withstand long intervals between milking and even the practice of single milking (one milking per day). Indeed, the removal of one milking per day indicates a greater loss of milk in breeds with smaller cistern udders [4]. In addition, the udders with rather horizontal teats and inserted high relative to the base of the cisterns are associated with the increase in the fraction of milk drip, requiring a manual intervention of massage and udder movement to collect the milk not extracted by the machine.
\nIn Murciano-Granadina goats, positive correlations between teat length and milk flow (r = 0.55) and between teat surface (r = 0.47–0.58) and residual milk were reported [23]. In the Saanen goats, a positive correlation (r = 0.65) was found between the circumference of the udder and daily milk production.
\nUnlike other dairy animals, there has been little work on the study of mammary morphology in camels [24, 25, 26, 27, 28, 29]. A good udder in camels is characterized by well-developed and symmetrical neighborhoods with vertically implanted, uniform, and well-spaced teats [30]. In the same context, [28] reported that the length and depth of the udder in camels are of the same order of magnitude as those indicated for cows [6] and for buffalos [31]. In camels, the teats placed very close to each other and sometimes fused are frequent. Juhasz and Nagy [32] showed a great heterogeneity in the morphology of the udder and teats in camels. They defined at least five different forms of teats. Ayadi et al. [28] found that daily milk production is positively correlated with teat distance (r = 0.61), udder depth (r = 0.29), and breast vein diameter (r = 0.34). The conformation of the udder in camels varies considerably according to the breed, the age, and the stage of lactation. Indeed, [25] reported that camels’ teat length varies with parity with shorter teats in primiparous (3.40 cm) than multiparous (6.10 cm).
\nRecently, for the development of a dromedary selection program according to the udder and teat typology adapted to mechanical milking, [33] proposed a 5-point linear scoring template for evaluating the udder of dairy camels based on five main traits.
\nA functional mammary gland is an exocrine gland consisting of a tubuloalveolar epithelial tissue and a stroma. In order to fulfill its production function, the udder is richly vascularized and innervated. There are two main categories of udders: the so-called udders composed without cistern (case of rodents and primates) and the so-called udder simple cistern (case of ruminants).
\nIn the ruminant udder, it is possible to distinguish an alveolar compartment (alveoli and fine channels) from an interconnected cistern compartment (large canals and cistern). The volumes of milk accumulated in each of these anatomical compartments can be measured accurately. Milk was first evaluated by draining the milk accumulated in the cistern by insertion of a cannula into the teat canal; the alveolar milk is then recovered by milking followed or not by an injection of oxytocin [2]. The use of a cannula to drain milk has been widely used. By using this technique, the volume of milk may be overestimated (in addition to milk, a fraction of alveolar milk can be recovered by endogenous oxytocin secretion conditioned or linked to stimulation of the udder when introducing the cannula).
\nIntravenous injection of oxytocin receptor blocking agent (Atosiban), which inhibits milk ejection, has been developed [34, 35]. Milking after injection of Atosiban permits to collect the cistern milk; then oxytocin injection reverses the effect and the alveolar milk can be collected. The use of Atosiban is therefore recommended in ruminants [36]. Moreover, noninvasive in vivo imaging techniques (ultrasonography) have been used to measure cistern udder storage capacity [10, 11, 5, 13]. Certainly, whatever the measurement method, knowledge of the distribution of milk in the udder, as well as the kinetics of its filling according to the species, is particularly important to determine the appropriate intervals between milkings.
\nIn cows, the volume of milk contained in the alveolar compartment is preponderant since it represents between 70 and 80% of the total quantity of milk 12 hours after milking [2, 3, 5]. This fraction is about 50–75% in ewes [37, 38, 4] and reaches even 80–90% in goats [39]. The cisternal milk represented 3–19% of total milk in camels [28, 12, 26] and 5% in buffaloes [40]. These proportions may vary depending on the breed of animals but also on the stage of lactation. In addition, the volume of milk stored in the cistern increases during lactation because of the decrease in secretory tissue during lactation [41]. Likewise, the volume of milk is higher in multiparas [41]. This is due to the immaturity of the development of cisterns in primiparas [42]. Studies on milk accumulation in the udder after milking have been conducted in dairy ruminants.
\nRecently, [43] proposed a 6-point linear scoring template for evaluating the cisternal size of the udder of dairy cows (0 = absent cistern; 6 = very large cistern), evaluated by ultrasound according to the methodology of [5]. This classification optimizes the milking frequency according to the stage of lactation and the production system.
\nMilk production (quantity and quality of milk) is regulated at different levels: by genetic factors, diet, various endocrines, and environmental controls. One of the levers for acting on the metabolic and secretory activity of the udder is the frequency of milking. Generally, cows are milked twice a day with milking intervals ranging from 8 to 16 hours, though studies have been conducted to determine animal milking management systems that combine maximization of quantitative and qualitative production with reduced work constraints. Research showed that for a frequency of two milkings per day, a 12–12 interval would be beneficial for high-producing cows (3–5% gain over a 10–14 interval) [37], suggesting the appearance of a brake on secretion beyond a certain time limit. To determine this limit, several studies place it between 10 and 18 hours depending on the animals [44]. These differences could be due to inter-individual variations and could also be related to anatomical features of the udder.
\nIn fact, animals with large udder cistern produce more milk and withstand relatively longer intervals between milkings than animals with a small udder cistern, which cannot transfer their alveolar milk and in which a brake on the secretion is set up faster. Such an observation has been verified in cows [2, 5], ewes [37, 13], goats [39], and camels [45, 12]. Therefore, it has been shown that when milk can flow continuously from the udder, milk production increases [44].
\nThe consequences of reducing the number of milkings on ruminant milk production have been studied by many authors. Certainly, the passage from two milkings to a single milking per day leads to a loss of milk production from 10 to 50% in cows [42].
\nShort-term (1 week) trials of mid-lactation Friesian and Jersey cows from two milkings to one daily milking reported milk yield decreases ranging from 10 to 25% [2]. The responses would depend on the stage of lactation since the loss of production would be more pronounced for animals in early lactation than for animals at the end of lactation (−38 vs. −28%) [44]. This can be related to the anatomy of the gland since it is known that the proportion of milk stored in the cistern varies with relation to the stage of lactation in cows [46, 41]. In ewes, switching to one milking per day causes a decrease in production from 15 to 35% [47, 48, 49]. The lowest losses are reported in Sardi ewes, known for their high capacity for storage and high production capacity, while the largest losses are observed in pre-Alpine ewes with small tanks and low production.
\nIn goats, one milking per day leads to production decrease from 6 to 35% compared to two milkings per day [50]. As in cows and sheep, race and stage of lactation have an effect, which can be related to the storage capacity of the udder. Undeniably, the largest losses are recorded at the beginning of lactation [39], and the lowest losses are observed in Canary goats, with very large cisterns. Overall, a decrease in milking frequency causes production losses depending on the animal’s storage capacity. Finally, it seems that this milking practice increases the concentration of somatic cells in milk [44], the increase being more marked as the number of cells in the milk at the beginning of the experiment is important. In dairy sheep, switching to one milking per day does not significantly modify the composition of milk [47], whereas in goats, an increase in fat matter and casein concentrations is reported [39].
\nIn dairy ruminants, as time after milking increased, there is (i) an increase in alveolar distension, (ii) a decrease in udder blood flow, (iii) an increase in tight junction’s permeability, and (vi) an accumulation of putative feedback inhibitor of lactation [50, 51].
\nThe first signals of local regulation of mammary gland activity are probably the degree and duration of alveolar distension. Studies by [52] have shown that the amount of alveolar milk in goats is low compared to animals with a high volume of residual milk. Despite the size of the alveolar compartment of the udder of cows reaches its maximum around 16 hours after milking, the longer the interval increases beyond 16 hours, the more the cells are filled with milk. In fact, the increase in pressure following the accumulation of milk throughout the mammary ducts generally leads to an inhibition of the secretion of milk [44]. According to [53], the dilation of the mammary alveoli is accompanied by a decrease in prolactin concentrations when the milking frequency is reduced. Furthermore, the increase of the intra-alveolar pressure causes the compression of the mammary epithelial cells (CEMs) altering the activity of their cytoskeletons and thus the intracellular traffic of the constituents of milk.
\nDairy production and mammary blood flow are positively correlated throughout lactation, with the synthesis of 1 L of milk requiring the passage of approximately 300–500 L of blood regardless of the ruminant species [54]. The increase in intramammary pressure (IMP) related to milk accumulation decreases the mammary blood flow (−10% after 24 hours in cows) [55] and −50% after 36 hours in goats [56]. The availability of hormones and nutrients would be reduced in the gland, thus decreasing the rate of secretion. This decrease in mammary blood flow could also be related to the activation of the sympathetic nervous system by the accumulation of milk [57]. Draining more frequently would therefore avoid a decline in blood flow, which could be a limiting factor for milk production, although the latter hypothesis has not been confirmed in goats [58].
\nA regulating mechanism involved in the practice of a single milking per day acts on the tight junctions, leading to an increase in the alveolar permeability. Really, the change in the chemical composition of milk during the practice of daily milking can be attributed to an increase in the serum in milk, as a result of changing the permeability of tight junctions. Furthermore, the increased permeability of the tight junction is achieved at around 17–18 hours of milking in cows [51], 19–20 hours in sheep [13], beyond 21 hours in goats [39], and 16 hours in camels [45]. Indeed, the change of the permeability of the mammary epithelium membrane during the practice of a single daily milking suggests a rapid increase in the concentration of lactose in the blood plasma and increased serum protein in milk and content of milk in Cl and Na and a reduction in lactose and K [59].
\nThe causes of the decrease in milk production for daily single milking are not well known. Indeed, in dairy cows, it has been shown, reduction of the milking frequency in one quarter of the mammary gland and not in the other quarters, that the quantity of milk in the treated unit only once a day decreased [60]. The same results were observed in sheep and goats [61]. In addition, incomplete emptying of the udder causes a decrease in production [62]. In order to prevent engorgement, the mammary gland has a feedback mechanism on milk synthesis; it produces a glycoprotein that inhibits its synthesis. Therefore, frequent emptying reduces the amount of this inhibiting factor in contact with the CEMs. This local chemical factor with inhibitory activity on milk secretion, called feedback inhibitor of lactation (FIL) or lactation inhibitor factor (LIF), is a low-molecular-weight protein (7.6 kDa), which has been shown in goats [63]. The FIL reduces the secretion rate of milk in vitro [62] and in vivo [63] when in contact with the alveolar epithelium. It works by inhibiting the constitutive secretion of proteins by CEMs by reversible blocking of the early stages of the biosynthesis-secretion pathway. In addition, the FIL would also inhibit lactose synthesis. Finally, FIL would regulate the number of cell tissue by triggering apoptosis [54]. Indeed, incomplete milking or milking removals would allow an accumulation of the FIL in contact with the CEMs, which would explain the reductions in milk production described above.
\nRecently, serotonin (5-HT) has been proposed to be an autocrine/paracrine regulator of lactation in the mouse, humans, and more recently in the bovine. The enzymatic machinery necessary for 5-HT biosynthesis has been detected in the mammary epithelium [64]. Other researches support the concept that serotonin (5-HT) is a feedback inhibitor of lactation in the bovine [65].
\nIncreasing milking frequency in dairy cattle to more than two milkings per day has resulted in an increase in milk production without any negative effect on the health of the animal. There are various reasons for the practice of three milkings a day, namely, increase in the time of use of the milking machine, the size of the herd, and milk production. In fact, milking three times a day results in an increase in milk production from 3 to 39% compared to two times in dairy cows [66], 15–35% in ewes [47], 10–20% in goats [67, 62, 39], and 4–13% in camels [68, 45]. The response to increased milking frequency would be greater in high-producing, primiparous, and late-lactating cows [66, 69]. Erdman and Varner [70] in their review of 40 comparative studies of increased milking frequency reported that switching from 2 to 3 milkings per day resulted in a stable increase in milk production in terms of quantity (3.5 kg/day) and not by a proportional increase.
\nIn studies on the milking robot, it has been shown that cows, when given free time, are milked on average between 2.7 and 3.9 times a day [71]. In addition, when a rate of four milkings per day is applied for 4 weeks, a production increase of 14% is observed [2]. However, switching to six milkings per day for 2 days only increases production by 10–15% [8]. Such observations suggest that an interval between milkings of 6–8 hours is physiologically ideal for the animal and that there would be no advantage in increasing the rate of milking above four milkings per day in cows [53], as in ewes [47]. An increase in milking frequency would therefore allow improved persistence of production in goats and cows [2, 51].
\nThere are contradictions in the literature regarding the effects of switching to three milkings per day. For some, changes in milk composition at three milkings per day would be insignificant, while others report a decrease in milk fat compared with cows milked twice a day [8]. For some, this decrease would be greater for primiparous cows, while for others, the decrease would be greater for multiparous cows [66]. At the lactation scale, [69] noted a slight decrease in protein and casein concentrations in milk, enough to reduce cheese yield by 1.5%. Somatic cell milk content is used as an indicator of the microbiological quality of milk. Indeed, the number of somatic cells decreases when milking frequency increases [71]. On the other hand, [66] report that switching from two to three milkings per day in dairy cows increases the California mastitis test (CMT) score.
\nThe increase of milking frequency could lead to an increased release of lactogenic hormones which will stimulate the synthetic activities of the CEMs and allow a better persistence of the lactation. These hormones may, in addition to their metabolic effects, increase the number of secretory cells and thus increase the volume of milk secreted [72]. Indeed, even if it is admitted in ruminants that the CEMs deteriorate and that their number decreases progressively with the advancement of lactation, by triggering apoptosis [54], the activity of synthesis of remaining cells is unchanged [72]. This decrease in the number of cells would be modulated by the frequency of milking. The increase of milking frequency causes cellular hypertrophy followed by an increase in the number of CEMs by proliferation of new cells. In addition, an increase in enzyme activities, reflecting their potential for synthesis, is observed in response to an increase in milking frequency in goats [62], cows [2], and camels [45].
\nDeciding about the number of milkings per day for each ruminant is a key factor in optimizing the use of mechanical milking. Currently, this decision is primarily based on the production level and stage of lactation data, but no udder capacity is taken into account. Therefore, it is recommended to use ruminants with large cisterns in order to minimize the effect of hydrostatic pressure on the cells and consequently reduce production losses. In practice, we propose to use the evaluation of udder cistern area by ultrasonography as a criterion to estimate milk storage capacity in the udder in order to establish the appropriate milking frequency for each ruminant according to the production system.
\nResearch opportunities are open to broaden and consolidate this study. Indeed, the work on the heritability and the repeatability of this character “glandular cistern” is essential in order to incorporate it into the breeding programs for dairy ruminants.
\nIt has been several decades since an unknown fever dramatically emerged, close to the Ebola river, a small tributary of the great Ubangi river in the heart of the Congolese tropical forest of Africa. Since that time, even though the virus responsible for this new hemorrhagic fever has been identified and characterized, the natural history of the eponymic Ebolavirus remains largely unknown. The cradle of the virus remains enigmatic and the emergence of the Ebola fever unsolved. Indeed, the arcane of Ebolavirus natural history is still hypothesized, thanks to an elusive virus that always risen where it was not expected, violent and devastating, and surprising local populations and health systems, as well as the international scientific community. This Ebolavirus eco-epidemiology remains complex while the Ebola fever (alias Ebolavirus Disease) can be considered as an exemplary disease that can be eventually comprehended only with a transdisciplinary approach that has recently been promoted as a One Health concept. Indeed, it is only when we take into account all disease and virus drivers, including biotic and abiotic factors of the natural and human environments, that some mechanisms of the Ebolavirus disease emergence, such as spread and circulation, can be ultimately unveiled. For that, we have collected all information available, often estimated, from the time and place of the virus emergence long before the emerging event was identified as it and the epidemic phase was brought to public attention. Moreover, when available we also collect all data on potential natural and accidental hosts, weather and environment chorology, among other multiple factors potentially involved.
\nHistorically, Ebolavirus emerged in Central Africa in the late 1970s, and has re-emerged most recently with the active epidemic (April 2019) in the eastern Democratic Republic of Congo (DRC), by encompassing more than 24 epidemic events from Central to West Africa, to imported infected monkey from Asia to Virginia, and the emerging new Ebola species of the Philippines archipelago [1].
\nAmong the negative sense RNA viruses of the
Ebolavirus’ (EBOV) first emergence occurred in 1976, as two different EBOV species in two different places in sub Saharan Africa. The Zaire Ebolavirus (ZEBOV) species and the Sudan Ebolavirus (SUDV) were detected concomitantly, a few weeks apart, respectively in the Northeastern Equator province of the Democratic Republic of Congo, DRC (alias Zaire), and in the Bahr el Ghazal province of South Sudan. On the 26th of August 1976 ZEBOV was isolated from missionaries and local villagers of the Yambuku, in the rain forest close to the Ebola river. However, earlier in June 1976, the SUDV had broken out among cotton factory workers in Nzara, Sudan (now in South Sudan) [3].
\nThen, in 1989, the Reston Ebolavirus species surprisingly (RESTV) emerged in the US (!) and was identified during an outbreak of simian hemorrhagic fever virus in crab-eating macaques from Hazleton Laboratories (now Covance) of Reston county, Virginia. Such primate specimens were found to be recently imported from the Philippines. Then, in 1994 a fourth new species of Ebolavirus was isolated from chimpanzee leaving in the Tai Forest of Côte d’Ivoire and named Côte d’Ivoire ebolavirus (CIEBOV). Finally, in November 2007, a fifth Ebolavirus species, was detected from infected patients in Uganda in the Bundibugyo District and was subsequently identified by the eponymic name of Bundibugyo Ebolavirus [4].
\nBriefly and extraordinarily among the world of the viruses, the filovirus virion presents a bacilliform (filamentous) shape, like a Rhabdovirus, but presents unique pleomorphic figures with branches and other tortuous shapes. Ebolaviruses have also an unusual and variable long length - up to 805 nanometers (only some plant virus can compete to this filamentous extensive length). However, the internal structure is more classical with a ribonucleoprotein nucleocapsid, a lipid envelope and seven nanometers size spikes. The genome is non-segmented, single stranded RNA of negative polarity with lengths of about 18.9 kb that code for seven proteins, each one having a specific function [5].
\nEbolaviruses are known for their high case-fatality rate (CFR) with always less than 2/3 of survivors among the identified cases. ZEBOV, the most frequently isolated Ebolavirus species during the outbreaks, has the highest CFR, up to 90% in some instances, with an average of 83% for the past 37 years. The Uganda BDBV outbreak had a mortality rate of 34%. RESTV imported to the US did not cause disease in exposed human laboratory workers. The scientist performing the necropsies on CIEBOV infected chimpanzees got infected and developed a Dengue-like fever, fully recovered 6 weeks after the infection while treated in Switzerland.
\nDates and time make History. Indeed, the various reports on the emergence of Ebolavirus in Africa show discrepancies and lack accuracy, for multiple reasons (remote event, reports by different person or team, at different time…) but the only way to forge the history is to label the events with date, time and the environmental factors observed. On July 27, 1976, the first (known) victim to contract Ebolavirus was a cotton factory worker from Nzara, Sudan. Then, in Zaire (DRC) on September 1, 1976, the first Ebolavirus (Zaire ebolavirus, ZEBOV) victim was a teacher who had just returned from a family visit to northern Zaire (6 Jennifer Rosenberg Internet). These two events were the very beginning of the boundless journey of a deadly Ebolavirus outbreaks.
\nWhen the virus becomes epidemic in a human population, it does so weeks or months after the emergent event of the virus switching from its silent transmission in a natural cycle to a zoonotic/epidemic manifestation, revealed to the local health system. Let us see in more detail such emerging events of Ebolavirus species (ICTV, 2018) as there were reported or sometime interpreted, in time and place.
\nSudan ebolavirus (SEBOV) occurred when the first recorded SUDV broke out among cotton factory workers in Nzara, South Sudan in June 271,976. This was indeed, the first case of Ebolavirus infection recorded and confirmed and also reported as potentially exposed to chiropteran. Indeed, at the Nzara Cotton Manufacturing Factory this first patient was a cloth room worker where bats (mostly
Zaire ebolavirus (ZEBOV) was reported in the Mongala district of the Democratic Republic of Congo (DRC; alias Zaire) in August 1976, when a 44-year-old schoolteacher of the Yambuku village, became the first recorded case of Ebolavirus infection in DRC. Also, the schoolteacher travel earlier in August 1976 near the Central African Republic border and along the Ebola River, estimated 90 km NW from the village [6].
\nReston ebolavirus (REBOV) had its first emerging event as an imported infected cynomolgus monkey (
Cote d’Ivoire ebolavirus (CIEBOV) was isolated for the first time, and as an only known appearance, in November 1994, from wild chimpanzees presenting severe internal bleeding of the Taï Forest in Côte d’Ivoire, Africa. A researcher became infected when practicing a necropsy on one of these primates, he developed a dengue syndrome and survived. At that time, many dead chimpanzees were discovered and tested positive for Ebolavirus. However, the source of the virus was believed to be of infected western red colobus monkeys (
Bundibugyo ebolavirus (BDBV) was then discovered during an outbreak of Ebolavirus in the Bundibugyo District (Bundibugyo and Kikyo townships), on August 1st, 2007, in Western Uganda (Towner et al. [11]). BDBV second emerging event was observed in the DRC in August 17, 2012 in Isiro, Pawa and Dungu, districts of the Province Orientale [11].
\nWith the exception of REBOV in Philippines and CIEBOV in West Africa, all other EBOVs species emerged in the Central African region. Also, all EBOVs are known to emerged in the tropical rain forest during the inter-season between dry and rainy seasons. Also, REBOV appears to actively circulate in the tropical rain or moist deciduous forest of the Philippines [12].
\nOn several occasions, concurrent emerging events of Ebolavirus have been observed. Indeed, such events occurred in places geographically distant, independent, and unconnected. The Ebolavirus was isolated and the strains different, even they belonged to the same species of Ebolavirus, altogether in favor of a different origin from an elusive natural reservoir, thus eliminating the notion of leaping from one site to the other. In that matter, the following observations are a paradigm: From its inceptive emergence the Ebolavirus was identified in Sudan at the cotton factory and a few days later at Yambuku, Zaire. The Ebola Sudan and Ebola Zaire viruses emerged concurrently in 1976 in the Congo basin of Central Africa; More than 20 years later the virus emerged and reemergence from 1994 to 1996 in a different places in Gabon, in a successive and timely overlapping events but in unconnected areas from where different strains of the same EBOVZ were isolated [13]; More recently, during the 2014–2016 dramatic Ebolavirus disease (EVD) emergence of in West Africa where the virus emerged in late December 2013 of a 18-month-old boy from the small village of Meliandou (Guéckédou district, South-Eastern Guinea) believed to have been infected by bats [14], concurrently, in August 2013, the Ebolavirus reemerged in the Equator province of DRC - different places and different strain of ZEBOV [15].
\nIt is remarkable that most of these emerging events occurred during or close to the end of the rainy season which generally stretches from August to October in the domain of the Congo basin tropical rain forest.
\nAltogether, these observations are in favor of environmental factors of emergence favoring, when they occur synchronously in the same place, the spillover of the virus from its hidden natural cycle to an accidental and susceptible host. Therefore, these plural and concomitant emerging events play against the theory of Ebola virus diffusing in oil spot in Central Africa [16]. This original pattern of concurrent emergences could explain also the relative stability of the virus strains which remain for years in the same environment, and the interepidemic silences which require several fundamentals (i.e. concurrent risk factors) to be broken.
\nThe first evidence that showed that Ebola virus had previously circulated in areas without any known cases of disease came in 1977, near the Ebola outbreak in Tandala, DRC, just 200 miles west of the first known cases in 1976 [17]. Blood samples obtained from individuals in areas with no previous symptoms of Ebola were found to contain antibodies for Ebolavirus, indicating a previous or ongoing infection with that virus. Because subclinical illness is always a possibility with viral infections, the presence of these Ebolavirus-specific antibodies could only be explained by exposure to the virus, which is somewhat reasonable in an area that is endemic to the disease. But how do we know the true endemic zone of a virus such as Ebolavirus?
\nEndemic zones are primarily based on where disease can most likely be expected, and are determined by historical accounts of disease, as well as supplemental information such as where animals or insects that might transmit the disease are located. With respect to the Ebola virus, outbreaks that occur in Central Africa, in or near the Congo River Basin, are expected; outbreaks that take place elsewhere are unexpected and can be problematic, as was the case for the 2014–2016 West African outbreak. And yet, scientists have highlighted the presence of Ebola antibodies well outside the endemic zone for disease for decades.
\nIn the early 1980’s, research based at the Pasteur Institute in Bangui, Central African Republic, demonstrated for the first time that the population of central Africa presented natural antibodies against the Ebolavirus strains of Zaire and Sudan [3, 4]. Research also showed for the first time that several mammal species had Ebolavirus-reacting antibodies, including rodents, dogs, and others. Initially, the scientific community was skeptical of the findings, due to the type of antibody tests used, and because the prevalence of these antibodies was unbelievably dispersed and at a high level of prevalence. However, a 1989 follow-up study confirmed methodology and preliminary observations, and expanded the results to include similar observations in Cameroon, Chad, Gabon, and Republic of Congo (the latter two of these countries would have their first Ebola outbreaks in 1994 and 2001, respectively) [5]. Moreover, such Ebolavirus antibody prevalence was found in West Africa (e.g. Senegal, Chad, Sierra Leone), preceding the catastrophic 2014–2016 Ebolavirus outbreak [18]. Subsequent studies have determined that 20–25% of persons living in or near the Congolese rain forest are seropositive for Ebola, despite never exhibiting symptoms [19].
\nToday, Ebola antibody prevalence is widely distributed across the African continent in the absence of severe clinical presentation and/or outbreak manifestation. A 1989 study even found Ebola Zaire antibodies among people living in Madagascar, an island country that has never had a single known case of Ebola, and which has been geographically separated from continental Africa for 100 million years [20].
\nRisk mapping, including ecological and geographical distribution <10-13 cm/s first hour, and extended, highly sensitive and specific environmental and biogeographical models based on EBOVs susceptible mammalian biogeography in Africa, show a robust and precise potential distribution of EBOVs in Africa that clearly overlap the African tropical rain forest biome of the Guinea-Congo forests (including the Congo basin rain forest, and the Occidental relic of the Congolese rain forest spreading from Guinea to Ghana) and the southern band of the Sudan-Guinea Savanna [21].
\nAlso, as a result of potential Ebolavirus (or Ebolavirus antigen) exposure, serological markers have been found in vertebrates outside of Africa. With the exception of Philippines, where REBOV is known to circulate in monkeys and pigs, thus showing its ability to infect multiple animal species, in several instances serological evidence of Ebolavirus exposure has been detected in many vertebrates, particularly chiropterans [9]. Definitely, bat populations in Bangladesh and China present antibodies against ZEBOV and REBOV proteins [22, 23]. Ultimately, it appears that EBOVs are widely distributed throughout Africa, West and Central, and Asia. Moreover, risk mapping of filovirus ecologic niches suggests potential areas of EBOVs distribution in Southeast Asia [24].
\nThe unexpected detection of REBOV first in Virginia, for the reason we know, and then the astonishing discovery of its circulation and natural cycle in the Philippines gave a rethinking of the entire family of Ebola viruses previously known mainly on the African continent [25].
\nFrom these observation and facts, the potential circulation of EBOVs in its natural cycle appears much wider than expected, while the emerging events we can witness appears to be only a tip of the iceberg in the wide Congolese tropical rain forest.
\nThe fundamentals of emergence are changing in the heart of the rainforest and elsewhere: changing times, when the means of transmission switch from foot to motorbike, when knowledge conveyance has switched from paper reporting to the internet.
\nLet us examine the risk of expansion for Ebolavirus. Indeed, the factors of transmission of the virus to man and man to man are essential to take into account in this context. Moreover, it is extremely important to note that these factors are subject to permanent changes in societies whose trade and means of communication are drastically changing as a result of health systems, responses and preparedness for epidemics at national and international levels, policies, and the economy.
\nSo, with the experience gained for more than 40 years, the strategies of struggle are clearly defined, but the societal changes that are taking place make their application difficult and sometimes impossible (e.g., the 2019 outbreak in the DRC, where political institutions have prevented an adapted response). Situation and the epidemic are perpetuated.
\nThere is also a growing means of communication, both smartphones and motorized transport, to travel more quickly as ever, between the epidemic zone of EVD and the family [26].
\nThus, during the emergence of the Ebola virus in West Africa, all of this means of communication played a fundamental role in the regional spread of the epidemic, until it became a pandemic risk when the virus was exported to other countries of the African continent and, outside Africa in Europe and North America [27].
\nIt is known for several other transmitted viruses that during the inter-epidemic silences several factors can be responsible. In general mass herd immunity (natural of due to acquired immunization i.e. vaccine) of the permissive hosts force the virus in its natural cycle without apparent clinical manifestation in the hosts (e.g. Most by the arbovirus classically yellow fever, Dengue, Japanese encephalitis, West Nile, Zika etc.).
\nThe
If one were to describe the history of Ebola outbreaks, one could simply construct a timeline, with a point on the line for each outbreak. You could create this timeline with a varying number of points, depending on your methodology, but regardless of how you built your timeline, there would be spaces between these points. This is due to the nature of Ebola; it appears, it disappears, and it appears again. To the Ebola virus, these gaps are periods of convalescence. To us, they are periods of absence and mystery, and one of these gaps stands out as the most mysterious (Figure 1).
\nTimeline of Ebolavirus emergence. Emerging events (bars) red = EBOV; blue = SEBOV; green = BDBV; horizontal axis = years 1972–2018; vertical axis = no value. Numbers above brackets = years of silent inter-emerging event.
The CDC lists five Ebola outbreaks in the late 1970’s. The “first” Ebola outbreak took place in 1976, though we now recognize the event as two simultaneous and separate outbreaks. Between June and November 1976, 284 cases (151 deaths) of Ebola Sudan occurred near what is now Nzara, South Sudan; between September and October 1976, 318 cases (280 deaths) of Ebola Zaire occurred near what is now Yambuku, Democratic Republic of Congo (DRC). In November 1976, a researcher in England that was working with samples from the Nzara outbreak accidentally infected himself; CDC lists this accident as the third Ebola outbreak (the individual recovered). In June 1977, a child became sick and died from Ebola Zaire in Tandala, DRC though there was only one confirmed case, subsequent epidemiological investigations of the area uncovered several other historical, probable cases. Finally, between July and October 1979, 34 cases (22 deaths) of Ebola Sudan occurred, unbelievably, in Nzara, Sudan – the same community where the first cases of Ebola emerged just 3 years prior. In the span of just 39 months, the terror of Ebola had introduced itself to the world five times (638 cases, 454 deaths) and then… silence.
\nEbola would not reappear for 10 whole years, and even then, the subtype was Ebola Reston, which we now know does not affect humans. Though CDC lists four Ebola Reston outbreaks between 1989 and 1992, the world would not see another case of Ebola virus disease in humans until late-1994, in Gabon. Even then, the outbreak (52 cases, 31 deaths) was mischaracterized as yellow fever for several months. Perhaps the virus’s long absence from the spotlight had removed it from the collective consciousness in 1994, certainly in the presence of those pathogens that had been circulating and consuming our attention in the meantime.
\nThis fifteen-year disappearance of Ebola, particularly in light of its frequent and severe outbreaks in the late 1970’s, has perplexed researchers for decades. The mystery lay, to some extent, within the lack of complete knowledge of the virus reservoir, though scientists are now having their long-held suspicions in bats confirmed. It’s hard to detect disease when you cannot pinpoint the source. Surveillance and reporting have been another confounding element. How many times in that fifteen-year period was an illness misdiagnosed as yellow fever, dengue hemorrhagic fever, or some other similar illness, because of lack of knowledge or diagnostic capabilities, or simply because there was no health care around? We will probably never be able to answer this question. Finally, our perceived zone of endemicity at the time was limited to northern DRC and southern Sudan. Was the virus appearing elsewhere, unbeknownst to us? We certainly were not expecting it to emerge in Gabon in 1994, and Uganda in 2000, and West Africa in 2014 [31].
\nScientists today continue to be perplexed by the emergence of the virus. What brings Ebola out from its hiding place? Is its emergence/re-emergence tied to climate change? globalization? the changing interface between humans and wildlife? If it has to do with any of these increasingly significant factors, how do they explain the fifteen-year disappearance?
\nThese days, the virus comes and goes with some predictability—since 2000, outbreaks have approached a near-annual incidence, sometimes skipping a year, sometimes lasting more than a year. The periods between outbreaks are growing shorter. Is this because our capability to detect Ebola outbreaks is improving, or is the virus able to infect humans more frequently? One thing is for sure: the world knows that when one outbreak ends, another will eventually follow, and we need not wait 15 years.
\nSince the ZEBOV and SEBOV emergence, extended field studies have been conducted to discover the reservoir of EBOVs [32] including the 1976 first recorded DRC outbreaks and Sudan, the 1979 outbreak in DRC in 1979 and 1995 following the Kikwit outbreak, the same year in the Tai Forest and in 1999 in the Central African Republic [33, 34, 35, 36, 37, 38] . A total of more than 7000 vertebrates and 30,000 invertebrates were sampled and tested for the presence of EBOVs. Limited finding was inconclusive for an potential EBOVs reservoir status among all these animals. Moreover, while several animal species (Bats, birds, reptiles, mollusks, arthropods, and plants) were experimentally infected with ZEBOV, only two fruit bat species (
Also, historically, the first documented case of EVD in Sudan in 1976, the index case was located (by the World Health Organization) in a cotton factory far from the forest block, where the only wild significantly abundant species was an insectivorous bat species [21].
\nSince the discovery of EBOV in 1976, more than half of the epidemic outbreaks caused by EBOVs have broken down between Gabon and the DRC. Following the successive EBOV outbreaks in Gabon from 1995 to 2001 affecting several animal species non-human primates, and wild ungulates and responsible of the dramatic decline of great apes (gorilla and chimpanzee) populations in the region (Leroy et al. [16]), researchers engaged several missions of captures of wild animals in the forest areas affected by the recent past epidemics. Also, 1030 animals were captured and analyzed, only three species of fruit bats were found infected with the ZEBOV by PCR including:
Since then, many studies have converged in favor of the role of chiropters in maintaining EBOV in the wild (Caron et al. [42], Leendertz). In addition, a recent study of bats in Sierra Leone showed the association of an EBOV like with several species of bats (
Altogether, several fruit bats (
Interestingly, REBOV was also found associated with the bats in its natural habitat of the Philippines [51]. Also, again in this same
Moreover, several virus groups are known to hold bat-borne viruses including the coronaviruses, hantaviruses, lyssaviruses, lassa virus, Henipavirus, filovirus which are among the most severe of the emerging viruses [54, 55].
\nConclusively, this was the first evidence of chiropteran as a potential reservoir and/or vector of EBOV, while several wild animals, in particular great apes were find highly sensitive to EBOV infection. Also, if several species of chiropteran have been identified as a potential virus reservoir,
\nFrom all above observations, records and historical events of EBOVs emerging events, several fundamentals of emergence have been identified as well putative time and space of such events where, that is when the virus jump from the cryptic natural cycle of the reservoir-vector to manifest itself clearly as an open index case of infection in a susceptible host and the potential opening epizootic or epidemic chain.
\nAgain, from the literature numerous vertebrates appears to be permissive to infection by EBOVs, however, due to their ethology, including environmental habits, societal structure, density and their ability of intra and interspecies to mingle. Altogether primates appear highly susceptible to EBOVs infection including non-human primate apes, gorilla and chimpanzee, but also cercopithecids (e.g. colobus) but also small wild ungulates (e.g. forest duikers) and eventually domestic animals (e.g. dogs) [32, 56, 57, 58].
\nOne can summarize that EBOVs natural hosts belongs to chiropteran as a potential host reservoir represented mostly by Pteropodidae in Africa (REBOV and Roussetus; Bombali virus and Molossidae), and as secondary natural or accidental wild and domestic hosts including several other mammals: primates (Colobus, Cercopithecus), non-human primates (Gorilla, chimpanzee), wild ungulates (duikers) and, human primates. Also this needs to be taken into account with respect to other permissive species to EBOVs, indeed, as an example, if Roussetus spp. was shown to carry EBOVs reacting antibodies more recently
The African Rain forest of the Congolese basin appears to be the epicenter of EBOVs emerging events. More than 80% of the emerging events of EBOVs occurred in the Tropical zone under the influence of the (Intertropical converging zone, ITCZ) from five degree North to 5 degrees south and oscillating as much as 40 to 45° of latitude north or south of the equator based on the pattern of land and ocean beneath it [28] (Figure 2).
\nEmerging events of Ebolavirus and climate since the Ebola fever inception in Africa. Left = annual rainfall; right = annual temperature. To illustrate the association temperature/rainfall and emergence, the month of May was chosen because it is at this time of the year that we observe the most emergent events of the Ebola virus. Temperature and rainfall are expressed as an annual average for the period under consideration. The precise location of 32 Ebola emergent events are here integrated into the global climatic map of Africa. Only 30-year average values per month of rainfall are available for the study period (ref.: WorldClim world databases) as well for the average monthly temperature.
Temperature and precipitation data for Africa (average data computed from 1960 to 1990, 300 m resolution [HIJ 05]) were integrated with the distribution map of the emergent events of the Ebola virus and the values calculated for each of the emergence points [60].
\nOn all emergence points, the temperature at the time of emergence is not significantly different from the average annual temperature over 30 years. The difference in temperature between the moment of emergence and the average temperature (of 30 years monthly average) of the hottest month does not show any difference either. Emergence would not be directly related to temperature.
\nWhen we compare Ebolavirus emerging events time and the rainfall, there is strict quantitative correlation between rainfall and emergence: Most of the emergent events (93.8%) occurred during the rainy season (Figure 2). For precipitation values, there is a slightly statistically significant (p = 0.02) positive difference between the average precipitation of the month of emergence and the average of the monthly average precipitation (over 30 years), indicating that precipitations are higher when emergences occur. There is an even more statistically significant (p = 0.003) positive difference when considering precipitation of the month preceding the emergence. Emergence is therefore likely to be associated with rainfall intensity and the rainy season. 10/32 emergences occur at the beginning of the rainy season, 9/32 in the middle, and 11/32 at the end. Only 2/32 emergences occurred in the dry season.
\nWhen referring to land use (Figure 3) the temperature at the 6 emergence points in “Cropland” is highly significantly less (p = 0.005) than 15% (21.6°C) at temperature (24.4°C) to the 9 points in “Tree cover, broadleaved, evergreen, closed to open”, however the average temperature of the Cropland (21.6°) is to a degree less, significantly lower (p = 0.01) than that of the “Tree cover” (24.5°C).
\nEnvironmental factors surrounding Ebolavirus emerging event: Land use and places of Ebola virus emergence in Africa from 1976 to 2014. Land use from ESA 2015, 300 m resolution; red circle = putative place of the Ebola virus emergence (index case). Estimated Ebola emergence places are superimposed on the land use layer. The identification of the land use types were 32 points (red circle) representing the putative places of Ebolavirus emergence are superimposed and are distributed as follows: (1) cropland: 6, (2) herbaceous cover: 5, (3) cropland mosaic: 5 (> 50% natural vegetation vs. <50% tree, shrub, herbaceous cover), (4) tree cover with: (a) 15% of broadleaved, evergreen, closed to open: 9, (b) 15–40% of broadleaved, deciduous, open: 2, (5) flooded, fresh or brackish water: 1, (6) urban areas: 3, and (7) water bodies: 1. The limitations of this interpretation are linked to the accuracy of the location of Ebolavirus emergence sites (from literature and reports) and, to the evolution of vegetation cover over the past decades since the first emergence of the Ebolavirus occurred in Africa.
Ultimately, taking into account these environmental factors, when we look for an association between the emergent events of the Ebola virus and the characteristics of the places of these emergences (i.e. land use, temperature, rainfall) it turns out that the emergences are always in the zone of heavy rainfall, but nevertheless do not follow the moving of the rainy season. Moreover, these emergences remain always and remarkably close enough to the Equator, therefore in the equatorial forest area with a high hygrometry, and a moderate annual temperature. However, the temperature at the time of emergence is not significantly different from the average annual temperature (at the points of emergence) which does not allow to distinguish seasonal effect in the emergence-temperature relationship. Conclusively, we did not identify a seasonality associated with the time of emergence, however the emerging events occur in specific geographic zone characterized by several environmental factors. Finally, the emergence zones are in areas of Land Use with specific temperatures not related to seasonality. Ultimately, it is also remarkable that all these emerging events occurred in an area with a highly potential presence of apes, virus-sensitive hosts.
\nAlso, the EBOVs species are closely genetically related, their seems to occur by foci in nature. The host appears to be the same, natural or accidental, and the transmission done by direct contact with infected hosts or its biological products [50, 61]. Altogether, in the early 2000s, before the identification of chiropteran as a potential host-reservoir of the EBOVs, a hypothetic natural cycle was described empirically based on seasonal environmental climatic factors [55]. Then, taking into account bats as a potential reservoir-host, the question of virus transmission was central to consider while environmental factors appears to play a major role to the host and their natural cycle (Chiropteran physiology) (climate/fructification, chorology, bats physiology). Several factors of emergence were then listed including: Chronic infection, infected organs, virus shedding, close encounters between reservoir and susceptible hosts, food and water resource, seasonality, chorology (i.e. causal effect between geographical phenomena – season) in the tropical rain forest and the spatial distribution of chiropteran (i.e. index site of Ebola emerging events).
\nEpidemiological field surveys indicate that mass mortalities of apes and monkey species due to Ebola virus often appear at the end of the dry season, a period when food resources are scarce. Restricted access to a limited number of fruit-bearing trees can lead to spatiotemporal clustering of diverse species of frugivorous animals, such as bats, nonhuman primates, and other terrestrial species foraging on fallen partially eaten (by bats) fruits. These aggregates of wild animal species favor the contact between infected and susceptible individuals and promote virus transmission. The dry season aggregation of reservoir host species involved in natural maintenance cycles, augmented by incidentally infected secondary hosts serving as sources for intra- and interspecific transmission chains independent of repeated spillover from the reservoir host, provides an ecological setting for amplifying enzootic transmission of Ebola virus when a vertebrate hosts are concentrated around a scarce number of water sources [62].
\nIn addition to this dietary impoverishment, there are behavioral and physiological events occurring among bats during the tropical dry favor the contact frequency and intimacy between bats, which can promote transmission of Ebola virus to others and increase R0. As an example, megachiropteran fruit bats breeding activities and intraspecific competitions between males and grouped
(A) Understanding Ebolavirus enzootic and epidemics. Red arrows = cycles of transmission; dashed square = a putative natural cycle of Ebolavirus in Central Africa (see B). Fruit bats are considered to be a putative reservoir of Ebola virus in Central Africa after 2004; In 2009, several non-human primate epizootic are reported; 1976 was the first emerging events and subsequent epidemic chains in remote area of the rain forest and close by; 2012 showed a dramatic spread of the virus associated with motorized transportation and ground network; In 2014 urban epidemics are reported as well as a pandemic risk and become an international public health emergency. (B) Putative natural cycle of Ebolavirus in Central Africa. Red arrow indicates Ebolavirus transmission. Numbered red circle of transmission: (1) sylvatic inter- and intra-species transmission; (2) chiropteran migration; (3) chiropter to primate (close contact of dejection); (4) primate inter species (Cercopithecus/chimpanzee); (5) primate to primate (non-human primates); (6) non-human primate epizootic (gorillas); (7) chiropter to duikers; and (8) consumption of chiropteran infected food by shrew or wild pig.
Based on historical data and observations, the presented hypothesis of the natural cycle of Ebolavirus emergence prevail an inter-species spillover as the complex natural cycle involving several hosts (reservoir, vector, amplifier), as well as biotic and abiotic factors in a changing environment among other original features.
\nAlthough the natural cycle of EBOVs remains in the darkness of the rain forest, strong findings and comparative analysis of close parents of the filovirus throw some light to a potential natural cycle of EBOVs in Africa. EBOVs clearly appear linked to chiropteran and dependent for merging events in the environmental factors. Indeed, it appears that filoviridae are often associated with chiropteran while the emergence of the virus strains occurs as a sparse focus with a silent period of cryptic virus circulation. When virus transmission, i.e. spillover, from a hidden natural cycle, to accidental hosts occurs, it happened in a specific time-frame often linked to the season.
\nOne can retain is that the EBOVs complex natural cycle is yet not on entirely elucidated and certainly dependent on environmental factors – associated with a specific environment of the chiropteran species incriminated (i.e. Different territories, different cycle) - leading to multiple, sometime concurrent, temporally and timely emergence in focus.
\nAlthough, other hypothesis has been suggested elsewhere including the Ebola virus Disease as an arthropod borne disease among others [42], there is important fundamental matters to consider as well before providing more.
\nHowever, beyond these hypotheses, fundamental questions subsist in order to go further learn. We can cite in particular the mystery of kin between the Reston virus of Asia and the Ebola viruses of Africa, would there not be a missing link in a geographic area yet to discover. Do the filovirus exist in the Americas hidden in the darkness of the tropical forest? Also, the Ebolavirus seems genetically stable, related to particular species of chiropter, was it to think about a co-evolution of the host and the virus in this closed environment of the forest of the tropical? Today, with the endless epidemic unfolding in the DRC, should we revisit our tools and strategy of struggle in an ever-changing world? [64].
\nWe sincerely thank for their supports, brings to all the authors of this deep and never-ending research and scientific thought around an outstanding and fascinating subject: Georgetown University, Centaurus Biotech LLC., The DHS Emeritus Center for Emerging Zoonotic and Animal Diseases at Kansas State University.
\nAll authors do not have any conflict of interest whatsoever with this published manuscript.
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\\n\\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\\n\\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Article but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Article as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world. The Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\\n\\nSubject to the license granted above, copyright in the Article and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\\n\\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Article.
\\n\\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\\n\\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Article as a consequence of IntechOpen's changes to the Article arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\\n\\n3. CORRESPONDING AUTHOR'S DUTIES
\\n\\n3.1 When distributing or re-publishing the Article, the Corresponding Author agrees to credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen, when they are distributing or re publishing the Article.
\\n\\n3.2 When submitting the Article, the Corresponding Author agrees to:
\\n\\n• Comply with all instructions and guidelines provided by IntechOpen;
\\n\\n• Produce the Article with all due skill, care and diligence, and in accordance with good scientific practice;
\\n\\n• Submit all the corrections in due time as defined during the publishing process schedule.
\\n\\nThe Corresponding Author will be held responsible for the payment of the Article Processing Charge.
\\n\\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\\n\\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Article worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\\n\\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\\n\\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\\n\\n4. CORRESPONDING AUTHOR'S WARRANTY
\\n\\n4.1 The Corresponding Author represents and warrants that the Article does not and will not breach any applicable law or the rights of any third party and, specifically, that the Article contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Article is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Article has not been formally published in any other peer-reviewed journal or in a Journal or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication
\\n\\nAgreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Article to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Article was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Article on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Article attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Article and has the right to contact the Corresponding Author and any Co-Author until the Article is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Article,
\\n\\nIntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\\n\\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\\n"}]'},components:[{type:"htmlEditorComponent",content:"The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Journal Article:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Article who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author. Co-Author: All other Authors of the Article besides the Corresponding Author. IntechOpen: IntechOpen Ltd., the Publisher of the Journal.
\n\nJournal: The publication as a collection of Articles compiled by IntechOpen .
\n\nArticle: The original literary work created by Corresponding Author and any Co Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to publish, communicate to the public, reproduce, republish, transmit, sell, distribute and otherwise use and make available the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works, in electronic and print editions of the Publication and in derivative works and on any platform owned and/or operated by IntechOpen, throughout the world, in all languages, and in all media and formats now known or later developed.
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to create and store electronic archival copies of the Article, including the right to deposit the Article in open access digital repositories.
\n\n• An irrevocable, worldwide, royalty-free, perpetual, transferable, sublicensable, non-exclusive right to license others to reproduce, translate, republish, transmit and distribute the Article in whole, partial or adapted from and/or incorporated in or in conjunction with other works under the condition that the Corresponding Author and each Co-Author is attributed (currently this is carried out by publishing the Article under a Creative Commons 4.0 International Licence).
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Article but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Article as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world. The Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Article and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Article.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Article as a consequence of IntechOpen's changes to the Article arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Article, the Corresponding Author agrees to credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Journal in which the Article has been published as the source of first publication, as well as IntechOpen, when they are distributing or re publishing the Article.
\n\n3.2 When submitting the Article, the Corresponding Author agrees to:
\n\n• Comply with all instructions and guidelines provided by IntechOpen;
\n\n• Produce the Article with all due skill, care and diligence, and in accordance with good scientific practice;
\n\n• Submit all the corrections in due time as defined during the publishing process schedule.
\n\nThe Corresponding Author will be held responsible for the payment of the Article Processing Charge.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Article worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Article does not and will not breach any applicable law or the rights of any third party and, specifically, that the Article contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Article is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Article has not been formally published in any other peer-reviewed journal or in a Journal or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication
\n\nAgreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Article to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Article was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Article on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Article attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Article and has the right to contact the Corresponding Author and any Co-Author until the Article is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Article,
\n\nIntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\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. 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But the blood-flow measurement inside the heart is difficult. There are many reasons behind it. The deep range and fast blood-flow are difficult to measure because of limitation of acoustic velocity. Moreover, strong heart valve signals mix into the blood-flow signal. Against such difficulties, the statistics mathematical model was applied to analyze many clinical data sets. The system identification method based on the mathematical model could realize a new blood-flow measurement system that has ultrasound Doppler information as input and electrocardiogram as output.",book:{id:"4655",slug:"applications-of-digital-signal-processing-through-practical-approach",title:"Applications of Digital Signal Processing through Practical Approach",fullTitle:"Applications of Digital Signal Processing through Practical Approach"},signatures:"Baba Tatsuro",authors:[{id:"65121",title:"Dr.",name:"Baba",middleName:null,surname:"Tatsuro",slug:"baba-tatsuro",fullName:"Baba Tatsuro"}]},{id:"24302",title:"Multiple-Membership Communities Detection and Its Applications for Mobile Networks",slug:"multiple-membership-communities-detection-and-its-applications-for-mobile-networks",totalDownloads:4095,totalCrossrefCites:4,totalDimensionsCites:4,abstract:null,book:{id:"599",slug:"applications-of-digital-signal-processing",title:"Applications of Digital Signal Processing",fullTitle:"Applications of Digital Signal Processing"},signatures:"Nikolai Nefedov",authors:[{id:"66756",title:"Dr.",name:"Nikolai",middleName:null,surname:"Nefedov",slug:"nikolai-nefedov",fullName:"Nikolai Nefedov"}]},{id:"49358",title:"Optical Signal Processing for High-Order Quadrature- Amplitude Modulation Formats",slug:"optical-signal-processing-for-high-order-quadrature-amplitude-modulation-formats",totalDownloads:1990,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In this book chapter, optical signal processing technology, including optical wavelength conversion, wavelength exchange and wavelength multicasting, for phase-noise-sensitive high-order quadrature-amplitude modulation (QAM) signals will be discussed. Due to the susceptibility of high-order QAM signals against phase noise, it is imperative to avoid the phase noise in the optical signal processing subsystems. To design high-performance optical signal processing subsystems, both linear and nonlinear phase noise and distortions are the main concerns in the system design. We will first investigate the effective monitoring approach to optimize the performance of wavelength conversion for avoiding undesired nonlinear phase noise and distortions, and then propose coherent pumping scheme to eliminate the linear phase noise from local pumps in order to realize pump-phase-noise-free wavelength conversion, wavelength exchange and multicasting for high-order QAM signals. All of the discussions are based on experimental investigation.",book:{id:"4655",slug:"applications-of-digital-signal-processing-through-practical-approach",title:"Applications of Digital Signal Processing through Practical Approach",fullTitle:"Applications of Digital Signal Processing through Practical Approach"},signatures:"Guo-Wei Lu",authors:[{id:"174507",title:"Associate Prof.",name:"Guo-Wei",middleName:null,surname:"Lu",slug:"guo-wei-lu",fullName:"Guo-Wei Lu"}]}],onlineFirstChaptersFilter:{topicId:"561",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,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:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,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. 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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. 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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. 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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},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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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). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",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. 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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. 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The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/309674",hash:"",query:{},params:{id:"309674"},fullPath:"/profiles/309674",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()