“Depression (−)”: HCV patients without depression, “Depression (+)”: HCV patients with depression following IFN-α therapy [47]. HCV, hepatitis C virus; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
\r\n\tReduction of inefficiencies, cost, and environmental impact are the main topics of energy engineering. Improving the individual technologies becomes more challenging from year to year as thermodynamic inefficiencies approach unavoidable levels. The chapters to be presented in the book aim to cover a wide range of: processes from low-temperature processes associated with air separation of liquefaction of gases to the high-temperature processes of combustion; from micro thermodynamic processes associated with the structure of materials to the macro thermodynamic processes associated with complex energy-conversion and chemical energy-intensive plants; application of new concepts such energy analysis; combination of thermodynamics and environmental sciences, and many other interdisciplinary concepts including modern applied thermodynamics; evaluation criteria based on the availability of primary energy resources, the efficiency of available energy technologies, as well as their economic and environmental methods to ensure that the scientifically-based evaluation and optimization methods are adequate and comprehensive.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:null,priceUsd:null,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"a8122d2875513b75741cacfd07cf65fb",bookSignature:"Prof. Tatiana Morosuk",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8365.jpg",keywords:"Applied Thermodynamics, Energy Resources, Energy Analysis, Entropy Analysis, Exergy Analysis, Energy Engineering, Energy-Conversion System, Economic Analysis, Ecological Analysis, Optimization",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 28th 2018",dateEndSecondStepPublish:"June 18th 2018",dateEndThirdStepPublish:"August 17th 2018",dateEndFourthStepPublish:"November 5th 2018",dateEndFifthStepPublish:"January 4th 2019",remainingDaysToSecondStep:"3 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"193888",title:"Prof.",name:"Tatiana",middleName:null,surname:"Morosuk",slug:"tatiana-morosuk",fullName:"Tatiana Morosuk",profilePictureURL:"https://mts.intechopen.com/storage/users/193888/images/system/193888.jpeg",biography:"Professor Tatiana Morosuk (Tetyana Morozyuk) is the Head of the Department “Energy-Based Methods for Refrigeration Systems” at the Technische Universität Berlin, Germany. She studied refrigeration engineering in the Odessa State Academy of Refrigeration, Ukraine, and received her diploma in 1990. She received her Ph.D. in 1994 and Professorship in 2001, all in the Ukraine.\nProfessor Morosuk has over twenty years teaching experience in the fields of refrigeration, energy engineering, and applied thermodynamics. She is associated with several scientific organizations as well as many international energy-related conferences and recognized international journals. She serves as an associate editor for the following international journals: “International Journal of Energy and Environmental Engineering” (Springer), “International Journal of Natural Gas Science and Engineering” (Elsevier), “International Journal of Energy Research” (Wiley), “Energies” (MDPI), “Entropy” (MDPI), and “Journal of Energy Resources Technology” (ASME).\nProfessor Morosuk’s areas of scientific activities include the application of energy-based methods to the improvement of the thermodynamic, economic, environmental performance of different power generation systems, refrigeration/cryogenic systems and chemical plants. Particular attention is given to hydrogen economy, systems associated with the liquefaction of natural gas and the regasification of LNG, alternative refrigeration processes for sustainable industrial and commercial applications, and smart energy supply and use in industrial parks, including innovative concepts of liquid air energy storage. She is the author or co-author of 7 books and 12 book chapters as well as more than 300 publications and 10 patents. Fourteen Ph.D. theses and more than 100 master theses have been successfully completed under her supervision/co-supervision. Prof. Morosuk has vast administrative experience being the study dean of four international master’s programs in Germany, and the Head of the Energy Engineering Department at TU Berlin Campus El Gouna. Tatiana Morosuk is professor of Technische Universität Berlin, Germany. She studied refrigeration engineering in the Odessa State Academy of Refrigeration (Diploma in 1990), Ph.D. in 1994 and Professorship in 2001, all in Ukraine. The main objective of her research is to increase the sustainability of energy conversion systems from the thermodynamic, economic and ecological viewpoints. These activities in research and teaching cover a wide range of applications from power plants to refrigeration/cryogenic processes, and energy-intensive chemical plants. This includes smart energy supply and use in industrial parks, implementation of renewable energy, and innovative concepts of CO2 technologies. She is the author/co-author of 7 books and approximately 400 publications. Professor Morosuk is the director of the Institute for Energy Engineering at TU Berlin and the study dean of the four international master programs.",institutionString:"Technical University of Berlin",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Technical University of Berlin",institutionURL:null,country:{name:"Germany"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"194667",firstName:"Marijana",lastName:"Francetic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/194667/images/4752_n.jpg",email:"marijana@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"8394",title:"Low-temperature Technologies",subtitle:null,isOpenForSubmission:!1,hash:"be68d10255b1c1c72aef7caddf946e34",slug:"low-temperature-technologies",bookSignature:"Tatiana Morosuk and Muhammad Sultan",coverURL:"https://cdn.intechopen.com/books/images_new/8394.jpg",editedByType:"Edited by",editors:[{id:"193888",title:"Prof.",name:"Tatiana",surname:"Morosuk",slug:"tatiana-morosuk",fullName:"Tatiana Morosuk"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"65623",title:"Thyroid Cancer and Acromegaly",doi:"10.5772/intechopen.84541",slug:"thyroid-cancer-and-acromegaly",body:'\nAcromegaly is a rare disease that results from the oversecretion of growth hormone (GH) and subsequent insulin growth factor I (IGF-I) [1]. It is associated with important complications that may reduce life expectancy of these patients [2, 3].
\nMost acromegalic patients die from cardiovascular, cerebrovascular, or respiratory diseases [3, 4]. Nevertheless, in the past two decades, some studies have also described an association between acromegaly and an increased risk of some cancers such as colorectal and thyroid cancer (TC), which is the most common endocrine malignancy, among others [5].
\nPart of the difficulty in determining the true incidence of cancer in this population is due to the relative rarity of acromegaly [6]. On the other hand, with improvement in surgical and radiotherapeutic procedures as well as advances in medical treatment, an increase of the survival rate of patients with acromegaly has been shown. As a result, patients may have a longer exposure to high GH levels [7].
\nAs the prevalence of thyroid cancer has been shown to increase among patients with acromegaly, this should draw attention for clinicians to investigate thyroid disease, particularly thyroid cancer.
\nThe association between acromegaly and TC is supported by preclinical data showing that GH-IGF system plays an important role in cancer development and progression [6]. However, clinical studies that addressed the association between acromegaly and cancer produced controversial results, partly due to the different methodological approaches used (case-control and population-based designs) [8].
\nA comprehensive meta-analysis showed an increased risk of both nodular thyroid disease (NTD) (OR = 6.9, RR = 2.1) and TC (OR = 7.5, RR = 7.2) in acromegaly. It showed a prevalence slightly below 60% of NTD and of around 4% of TC [8]. Within this context, a consistent Brazilian multicentric study with 124 acromegalic patients in a case-control design showed a higher prevalence of 7.2% for TC and 0.7% in the control group [9].
\nThese findings may result from the fact of improving diagnostic and treatment of acromegaly extending the life duration which increases the prevalence of both benign and malignant neoplasms [3, 4, 5, 6, 7, 8, 9, 10, 11].
\nOn the other hand, the co-occurrence of autoimmune thyroid diseases and acromegaly is not common. So far only a handful of cases of Graves-Basedow disease in acromegalic patients have been reported, while Hashimoto’s disease occurs more frequently (4.6%) [12, 13].
\nThe pituitary gland integrates hormonal signs that control several homeostatic processes such as metabolism, growth, and reproduction. Cell clusters localized in the anterior pituitary, somatotrophs, secrete GH responsible for cellular proliferation through membrane-bound growth hormone receptor (GHR) present in various organs and systems [14]. The interaction between GH and GHR results in activation of intracellular protein Janus kinase 2 (JAK2). As shown in Figure 1, once phosphorylated JAK2 activates the signal transducers and activators of transcription (STAT) protein that is translocated to the nucleus and initiates transcription of genes in response to GH [15], the STAT is able to bind to IGF-I promoter regulating the transcription of this gene [16]. Thus, the presence of GH can induce the synthesis of IGF-I that occurs mainly in the liver and is composed of 70 amino acids and has mitotic and anti-apoptotic effects [1].
\nActivation of JAK/STAT pathway mediated by GH (growth hormone). (a) JAK/STAT pathway components are inactive. (b) GH leads to dimerization of its receptor promoting phosphorylation of JAK and consequent activation of STAT proteins. (c) Once activated, STAT forms dimers that are translocated to the cell nucleus. (d) The STAT dimers in the nucleus are capable of binding to IGF-I promoter, initiating the transcription of this gene.
In the vast majority of cases, the excess of GH in acromegaly is originated from proliferating somatotrophs (somatotropinoma). The pituitary adenomas are of monoclonal origin, indicating that the tumor rises from a single cell that acquires proliferative advantage [17]. The primary defect that leads to development of somatotropinoma may result from genetic and epigenetic alterations inducing the activation of oncogenes or inactivation of tumor suppressor genes [1]. Mutations in the alpha subunit of transmembrane G protein is observed in 40% of GH-secreting tumors [1]. This abnormality may cause constitutive activation of cyclin AMP (cAMP) and consequent hypersecretion of GH. Loss of expression of proapoptotic molecules such as GADD45γ (growth arrest and DNA damage-inducible 45γ protein) and overexpression of oncoproteins, including PTTG (pituitary tumor-transforming gene), are phenomena also observed in pituitary adenomas [17, 18].
\nMost cases of acromegaly occur sporadically; however, approximately 5% of cases may be related to inherited diseases such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA) [17]. Germline mutations in aryl hydrocarbon receptor-interacting protein (AIP) gene seem to be the most frequent genetic alteration detected in sporadic and familial acromegaly patients [19]. The MEN1 and CNC are caused mainly by defects in genes MEN1 (menin) and PRKAR1A (regulatory subunit type 1 alpha), respectively [17].
\nThe serum GH excess may promote proliferation and suppress apoptosis in many tissues [15]. Thus, it is suggested that acromegaly is responsible for the increased risk for development of many malignancies. PTC is the most common thyroid cancer observed in acromegaly [7, 9]. This type of pituitary tumor can also be associated with benign thyroid conditions such as diffuse and nodular goiters [9].
\nThe mechanism of thyroid carcinogenesis in acromegaly is attributed to an autocrine/paracrine loop for GH/IGF-I in tumor tissue [8]. As the thyroid follicular cells also produce IGF-I and express genes encoding IGF-IR, the long-term exposure of thyrocyte to high GH/IGF-I levels may work synergically with this loop in promoting goiter development and malignant transformation [20].
\nAs shown in Figure 2, the molecular oncogenesis of PTC is mainly related to deregulation of mitogen-activated protein kinase (MAPK) signaling pathway and involves point mutations in BRAF and RAS genes and RET/PTC gene rearrangements [21, 22]. Analysis of these molecular markers can have diagnostic and prognostic implications in thyroid cancer.
\nMAPK and PI3K pathways. (a) Growth factors bind to receptor tyrosine kinase and trigger the activation of (b) MAPK and/or (c) PI3K-AKT. (d) The signaling mediated to both pathways promotes the transcription of gene associated to different cellular processes such as proliferation and survival.
BRAF (B-type RAF kinase) is a serine threonine kinase considered the most potent MAPK activator. This protein regulates important cellular processes such as proliferation, differentiation, and apoptosis [1].
\nIn PTC, the main mechanism for activation of BRAF gene is a point mutation that promotes a substitution of nucleotide thymine by adenine at position 1799. This single nucleotide change promotes the replacement of valine by glutamate at protein residue 600 (V600E). The BRAF V600E mutation is the most frequent genetic abnormality reported in thyroid carcinomas in the general population, particularly in PTC [21].
\nIn acromegalic patients, the importance of BRAF V600E mutation on PTC carcinogenesis is still not well defined. In an Italian cohort of acromegalic patients, the BRAF V600E mutation was detected in 70% of cases with PTC, suggesting that this mutation is the main genetic driver of neoplastic transformation of thyroid cells in acromegaly [23]. On the other hand, other studies have demonstrated that the BRAF V600E mutation is infrequent in patients PTC with and without acromegaly [20, 24]. In these reports lower prevalence of this genetic alteration in acromegalic patients with PTC than non-acromegalic cases with PTC was verified. These results suggest that BRAF V600E mutation may not be a main mechanism of malignant transformation of thyroid cells in patients with acromegaly.
\nThe HRAS, KRAS, and NRAS are homologous gene members of the RAS (retrovirus-associated DNA sequences) family. These genes encode GTP-binding proteins localized at the inner superficial of the cell membrane involved in signaling MAPK and PI3K-AKT pathways [1]. Together, RAS mutations are the second most frequent molecular alteration found in thyroid cancer, occurring in 10–20% of PTC cases and 40–50% of follicular carcinomas [22].
\nPoint mutations are commonly restricted at codon 61 of the HRAS and NRAS genes and at codons 12 and 13 in the KRAS gene. RAS mutations in thyroid cancer have been associated to favorable prognosis such as tumor encapsulation and absence of metastases but also may represent a poor prognostic factor predisposing to cellular dedifferentiation and anaplastic transformation [22]. NRAS codon 61 mutation has been referred as the most frequent genetic alteration in PTC patients with acromegaly. Aydin et al. pointed out that patients with NRAS codon 61 mutation have aggressive histologic features such as vascular and capsular invasion [24]. However, another study revealed no case in a cohort of acromegalic patients with PTC-harbored RAS mutations [23]. These contradictory findings indicate that the importance of RAS mutational status in thyroid oncogenesis in acromegaly remains to be clarified.
\nThe RET is a proto-oncogene that encodes a receptor-type tyrosine kinase with three domains: extracellular, transmembrane, and intracellular tyrosine kinase. The activation of this gene can contribute to the development of several neoplasms [25]. Rearrangements of RET that originated from fusion with unrelated genes (RET/PTC rearrangements) have been reported in thyroid follicular cells [26]. This genomic alteration can produce a chimeric oncoprotein with inappropriate tyrosine kinase activity able to continually stimulate the MAPK and PI3K-AKT pathways [26]. Among the fusion variants of RET, the rearrangements RET/PTC1 and RET/PTC3 are the most frequent in thyroid cancer. Whereas in RET/PTC1 the RET gene is fused to CCDC6 (known as H4), in RET/PTC3 the rearrangement occurs with NCOA4 (known as ELE1 or RFG) [25]. RET/PTC rearrangement appears to be an important mechanism of thyroid carcinogenesis, but its frequency has oscillated in different reports. This genetic abnormality was not detected in PTC patients with acromegaly [24], although studies with this approach are rare in acromegaly.
\nBesides the potential classic marker, other molecules have been evaluated in relation to their implication on PTC development in acromegaly, among them are IGF-I, IGF-IRβ, AIP, AHR, and galectin-3 (Gal-3) [20, 23, 24, 27].
\nThe analysis of immunohistochemical staining for IGF-IRβ revealed a high expression of this receptor in PTC samples [20]. Although differences in IGF-IRβ tumoral staining between PTC patients with and without acromegaly have not been observed, this marker had significantly less expression in adjacent normal tissue of patients with acromegaly. These data suggest that high GH levels may trigger autocrine and paracrine effects of IGF-I in thyroid follicular cells resulting in overexpression of IGF-IRβ in tumor tissue of acromegalic patients. In line with these results, it was observed that PTC patients with acromegaly have higher expression of IGF-I than PTC cases without acromegaly [27]. Additionally, an intense expression was verified of Gal-3 in PTC with acromegaly, speculating a possible influence of this protein on thyroid carcinogenesis.
\nAs previously mentioned, inactivation of AIP gene is frequently reported in pituitary tumors. However, this genetic abnormality seems not to be determinant to thyroid carcinogenesis in acromegalic patients [23]. Furthermore, there are no differences in AIP protein expression between PTC in patients with and without acromegaly. Although immunohistochemical analysis for AIP receptor (AHR) has shown strong staining of PTC samples carrying BRAF V600E compared with wild type, differences were not found in AHR staining between PTC in acromegalic and non-acromegalic patients [23]. Thus, molecular alterations in AIP and AHR cannot be related to PTC carcinogenesis in acromegaly.
\nNTD seems to be significantly more frequent in patients with acromegaly. Even palpable thyroid nodules occur significantly more often in these patients [9, 13].
\nPeriodic thyroid ultrasound (US) and careful evaluation of detected lesions are important parts in the follow-up of acromegalic patients. The sonographic characteristics considered to be suspicious of TC, such as microcalcifications, irregular margins (infiltrative and microlobulated), taller than wide shape, and rim calcifications with small extrusive soft tissue component (evidence of extrathyroidal extension), are the same of the general population with NTD [5, 9].
\nFine-needle aspiration (FNA) is the procedure of choice in the evaluation on NTD, and it should be performed when clinically indicated according to nodule’s size and US appearance. The FNA cytology result must be reported using the Bethesda System for Reporting Thyroid Cytopathology [9, 28].
\nIn summary, as the risk of malignancy in thyroid nodules in these patients is about 8%, which is in the range considered for the general population, the management of NTD should follow the current guidelines [9, 28].
\nAlthough there is a risk of TC in acromegalic patients, its clinical behavior does not seem to be different [5]. Therefore, acromegalic patients with TC may be treated with total thyroidectomy or hemithyroidectomy according to its FNA result and size and the presence of clinically apparent metastatic lymph nodes [28].
\nBefore surgery, we suggest that all acromegalic patients should do a preoperative voice assessment (preoperative laryngeal exam—laryngoscopy) because they frequently have soft tissue thickening and edema of the tongue, pharynx, and upper airways [3]. Also, they must have a careful evaluation of comorbidities as hypertension, diabetes mellitus, and cardiovascular disease [3].
\nAfter surgery, these patients may or may not receive radioiodine depending, if it is a differentiated TC, on its risk of recurrence [28]. Studies about the relationship between medullary thyroid cancer (MTC) and acromegaly are lacking.
\nThe frequency of US and laboratory tests during TC follow-up should follow the current guidelines.
\nNTC and TC are more frequent in acromegalic patients. On the other hand, the studies about potential mechanisms involved in this association between TC and acromegaly are still scarce, and besides they include small sample sizes. Furthermore, in these few reports, there is no marker clearly implicated on diagnosis or prognosis of PTC. Thus, further studies with this approach are needed.
\nWe suggest that acromegalic patients should be routinely screened by thyroid ultrasound and during their follow-up as necessary. Its management should follow the current guidelines. This is very important because it may allow early diagnosis and treatment of TC.
\nWe would like to thank Doctor Gilvan Nascimento Cortês for the review of the manuscript.
\nThere is no conflict of interest.
Hepatitis C virus (HCV) infection is a global health problem. Up to 85% of HCV-infected patients may develop long-term chronic hepatitis C (CHC), a disease state associated with serious clinical sequela, including liver cirrhosis, hepatic fibrosis, and hepatocellular carcinoma [1, 2, 3, 4]. It has been estimated that up to 20% of CHC patients will develop hepatic cirrhosis over a 20–25-year period, and these individuals are at an increased risk for developing end-stage hepatic diseases or hepatocellular carcinoma [4]. Therefore, aggressive antiviral treatments to successfully induce viral remission constitute a major strategy for reducing the morbidity and mortality associated with CHC.
Immunotherapy with interferon-alpha (IFN-α) is commonly used to treat CHC and several types of malignancies owing to its antiviral, antiproliferative, and immunoregulatory effects [5]. In clinical trials, more than 50% of CHC patients treated with combination therapy using IFN-α and ribavirin achieved a sustained viral response, defined as undetectable HCV in the blood 6 months following the end of treatment [4]. Despite the efficacy of IFN-α in CHC treatment, IFN-α therapy causes serious side effects; early signs include somatic symptoms (anorexia, pain, insomnia, fever, and fatigue). Prolonged therapy causes neuropsychiatric symptoms including depressive states, anhedonia, anxiety, and cognitive impairment. In particular, depression is a serious and frequently occurring side effect of IFN-α therapy, and this leads to discontinuation of the therapy in up to 45% of patients [6, 7]. Therefore, in order to avoid the discontinuation of IFN-α therapy owing to depressive symptoms induced by the cytokine, it is important to identify the risk factor(s) leading to the associated depressive symptoms.
A number of findings suggest that the neuropsychiatric side effects observed during IFN-α therapy may be linked to aberrations in the tryptophan (TRP)-kynurenine (KYN) pathway [8, 9]. Clinical studies have found that IFN-α therapy reduces plasma TRP and serotonin (5-hydroxythrptamine; 5-HT) levels [8] and increases KYN levels in plasma and cerebrospinal fluid (CSF). In addition, the KYN/TRP ratio, an index of indoleamine 2,3-dioxygenase 1 (IDO1) activity, is increased in patients receiving IFN-α therapy [8].
IDO1 is an extrahepatic enzyme that catalyzes the conversion of TRP to KYN, which can produce many neuroactive metabolites such as 3-hydroxykynurenine (3-HK), kynurenic acid (KA), and quinolinic acid (QUIN). Intriguingly, QUIN levels in CSF have been found to correlate with the severity of depressive pathology [10], and post-mortem studies have shown increased microglia QUIN levels in the frontal cortex of severely depressed patients [11].
In the current chapter, we present the findings of our latest study, which demonstrates the association between IFN treatment and changes in the TRP-KYN pathway in the blood of HCV patients. To do so, we investigated the effect of chronic Ifn gene expression on depression-like behavior and levels of brain TRP-KYN metabolites in mice. Our results suggest the possibility for the prediction of onset risk of depression as a side effect in HCV patients.
IFNs were first introduced in 1957 as antiviral molecules. Based on their receptor types on the cell membrane surface, IFNs are classified into type I and type II. IFN type I mainly consists of IFN-α/β, while IFN type II consists of IFN-γ. IFN type I is a family of cytokines in which their amino acid sequence similarity reaches 30–80%. They are produced by a wide variety of cells, including fibroblasts, epithelial cells, and hepatocytes [12, 13]. However, in most viral infections, plasmacytoid dendritic cells (pDCs) are probably the major source of these cytokines. In contrast, IFN type II (IFN-γ) is a single gene cytokine unrelated in structure to IFN-α/β, which is produced largely by macrophages, natural killer (NK) cells, and T lymphocytes [12].
The host response against HCV infection is first triggered when a pathogen-associated molecular pattern (PAMP), presented by an infecting virus, is recognized and engaged by specific PAMP receptors expressed on the host cells. This leads to the activation of signals that ultimately induce the expression of antiviral effector genes [14, 15] (Figure 1). For RNA viruses, protein, and nucleic acid products of infection or replication have been identified as viral PAMPs. These are engaged by specific toll-like receptors (TLRs) or nucleic acid-binding proteins that serve as PAMP receptors [15, 16, 17]. The viral RNA of HCV contains each of these PAMP signatures, and is adequate to trigger the host response when introduced into naïve cells [18, 19]. In hepatocytes, which is the target cell of HCV infection, independent pathways of retinoic acid-inducible gene I (RIG-I) and TLR3 signaling construct two major pathways of host defense triggered by double-stranded (ds) RNA [19, 20, 21]. Viral PAMP binding to RIG-I or TLR3 results in the phosphorylation and activation of interferon regulatory factor 3 (IRF-3) by TANK-binding kinase 1 (TBK-1) and I kappa B kinase ε (IKK-ε) [14, 22]. The dimer of phospho-IRF-3 translocates to the cell nucleus, interacts with its transcription partners, including CREB-binding protein (CBP)/p300, and binds to the cognate-DNA positive regulatory domain (PRD) in the promoter region of IRF-3 target genes, such as IFN-β [14, 23]. The engagement of PAMP receptors also leads to the synthesis of IFN-α/β, tumor necrosis factor (TNF), and a variety of other cytokines, which are largely produced by mainly pDCs that express TLRs in abundance. IFN-α/β produced by pDCs activates NK cells, thereby enhancing their cytotoxic potential and stimulating their production of IFN-γ. IFN-α/β produced by pDCs also modulates the activation of CD8+ T cells, which produce additional IFN-γ and represent the central players in the pathogen-specific adaptive immune response [12].
The host innate response to HCV infection. Adapted from Ref. [14]. (1) HCV RNA binding to RIG-I or TLR3 results in the activation IRF-3. The dimer of phospho-IRF-3 translocates to the nucleus, interacts with transcription partners and binds to the cognate-DNA PRD in the promoter region of IRF-3 target genes. (2) IRF-3 activation leads to the induction of IFN-β production. (3) Secreted IFN-β from the infected cells binds to the IFN-α/β receptor, and results in activation of the JAK-STAT pathway. The ISGF3 complex translocates to the nucleus, where it binds to the ISRE on target genes to direct ISG expression. IRF-7 is one of the ISGs and it is activated after expression through viral PAMP signaling. (4) The IRF-7 dimer and heterodimer with IRF-3 binds to VRE in the promotor region of IFN-α genes resulting in the production of various IFN-α subtypes and establishing a positive-feedback loop for IFN amplification. It is the IFN-α component of the host response that is exploited by the current IFN-based therapy for HCV infection [14].
IFN-α mediates a wide range of biological activities including antiproliferation, immunomodulation, and antiviral responses. IFN-α/β acts to induce the antiviral response in cells. These cells can be far from IFN-α/β production site and IFN-α/β interacts with specific cell surface receptors, type I IFN receptors (interferon-alpha receptor 1 (IFNΑR1) and IFNΑR2; Figure 1). IFNARs signal to the nucleus via Janus kinase-1 (Jak1) and tyrosine kinase 2 (Tyk2) phosphorylation of the signal transducers and activators of transcription (STATs) [24]. The classic IFN-α/β signaling pathways activate STAT1/STAT2 heterodimers and the trimeric IFN-stimulated gene factor (ISGF) complex containing IRF-9, which activate the expression of specific subsets of genes controlled by promoters containing interferon-stimulated response elements (ISRE; Figure 1) [15]. Interferon-stimulated genes (ISGs) are the genetic effectors of the host response, although the details of the signaling mechanisms by which IFN-α/β and IFN-γ induce the transcription of ISGs are still being defined [25]. IRF-7 is a transcription factor and an ISG. It is expressed in many tissue types, including complex liver tissue, in response to IFN. IRF-7 is activated after expression via viral PAMP signaling pathways that overlie with the IRF-3 activation pathway. IRF-7 phosphorylation, dimerization, and heterodimerization with IRF-3 lead to bind its cognate virus-responsive element (VRE) in the promotor region of IFN-α genes. Then, this binding results in the production of various IFN-α subtypes. The transcription effector action of IRF-7 also promotes diversification of the ISG response, establishing a positive-feedback loop that amplifies IFN production, and antiviral action [14]. This increases the plenty of RIG-I and viral PAMP signaling modules whose continued signaling acts to amplify IFN production and the host response. The medicinal administration of IFN-α promotes an antiviral reaction against HCV infection by stimulating ISG expression via the IFN-α/β receptor and the JAK-STAT pathway. In addition to stimulating ISG expression, IFN-α induces or promotes the maturation of immune effector cells, and enhances the production of other cytokines by resident hepatic cells to indirectly modulate the cell-mediated defenses and adaptive immunity to HCV [15]. Viral trigger and control of the host response may elucidate cellular tolerance for HCV RNA replication and influence the outcome of infection.
IFN-α has been shown to develop depression in many diseases, not only CHC, but also in melanoma, chronic myelogenous leukemia, and renal cell carcinoma [26]. However, CHC patients may be more susceptible to developing IFN-induced depression than patients with other disorders, possibly due to a baseline 5-HT system dysfunction. Depression in CHC patients may result from changes in platelet 5-HT function, with decreased 5-HT concentrations during CHC infection compensated for by a decrease in reuptake and metabolism [1]. Immune activation, particularly by IFN-γ, affects the catabolism of TRP, a precursor of 5-HT, by inducing expression of IDO1. IDO1 is the first and rate-limiting enzyme that converts TRP to N-formyl-L-kynurenine, which is further metabolized to QUIN (Figure 2). IFN treatment of CHC patients results in a decrease in plasma TRP and an increase in plasma KYN [8]. Another clinical study with cancer patients has shown that immunotherapy with IFN-α significantly increases the severity of depressive symptoms, which is related to a depletion of serum 5-HT and induction of the catabolism of TRP to KYN [27]. Thus, TRP catabolism switches from the 5-HT pathway to the KYN pathway, resulting in a decrease in 5-HT levels.
Schematic overview of the TRP-KYN pathway. IDO1 catabolizes L-TRP to N-formyl-L-kynurenine, which is converted to L-KYN by formamidase. L-KYN is further metabolized to AA by kynureninase (KYNU), to KA by kynurenine aminotransferases (KATs), and to 3-HK by kynurenine 3-monooxygenase (KMO). KMO is then metabolized to 3-HAA by 3-hydroxyanhranilate 3,4-dioxygenase (3-HAAO). 3-HAA is further metabolized to QUIN.
IDO1 is induced by several pro-inflammatory cytokines including IFNs (IFN-α/β, γ), TNF-α, and interleukin 6 (IL-6). It is also widely accepted that IFNs, especially IFN-γ, are essential factors for IDO1 induction since two ISREs and IFN-γ-activated site (GAS) element sequences are found in the 5′-flanking region of the IDO1 gene [28]. Recent preclinical studies in mice have demonstrated that pharmacological inhibition of IDO1 enzymatic activity or genetic deletion of IDO1 abrogates acute and chronic inflammation-dependent behavioral changes induced by peripheral or central administration of lipopolysaccharide (LPS) [29, 30, 31, 32, 33]. Additionally, it has been reported that peripheral administration of KYN alone can induce depression-like behavior in rats [34]. In a clinical study, patients receiving IFN-α therapy showed increases in the total Montgomery-Asberg Depression Rating Score (MADRS), an index of depressive symptoms similar to the KYN/TRP ratio; this indicates IDO1 activity and the KYN/KA ratio, which reflects a neurotoxic challenge [35]. These findings suggest that only TRP depletion itself may not be required for the induction of behavioral changes as a result of IDO1 activation; and that KYN and its neuroactive metabolites are more related to cytokine-induced depression-like behaviors than TRP depletion. However, it is still unclear whether direct activation of IDO1 and KYN metabolites plays a definitive role in the induction of depressive symptoms by IFN-α treatment.
In order to further clarify the relationship between the IDO1-induced KYN pathway and the development of depressive symptoms during IFN-α therapy, we conducted a study in which we measured TRP metabolites of the KYN pathway in the serum of HCV patients undergoing IFN-α therapy.
A total of 49 patients (32 males and 17 females; mean age 54.0 ± 2.3 years) suffering from CHC were recruited. Table 1 shows the clinical characteristics of patients with HCV. In this study, most of patients were treated with recombinant (r) IFN-α 2b or pegylated (PEG)-IFN-α 2b (21 patients (42.9%) received each medicine, respectively). Five patients (10.2%) were treated with natural (n) IFN-α, and others received PEG-IFN-α 2a (2.0%) and rIFN-α 2a (2.0%), individually. All interferons have almost the same efficiency and induce about the same activation of the KYN pathway [36]. No patient had a past record of psychiatric treatment, and all were off from depressive symptoms prior to IFN-α treatment. They did not take any antidepressant medications during the study period. At an average of 104.2 ± 15.8 days after the IFN-α administration, some patients presented with apathy, social isolation tendencies, melancholy, depressed mood, and an intention to stop IFN administration. Patients who felt depressed mood were referred for psychiatric evaluation and identified as major depressive disorder (MDD) by a psychiatrist. Nineteen of the HCV patients were diagnosed with depressive symptoms [depression (+)], while 30 of them did not present depressive symptoms [depression (−)]. The diagnosis to verify the incidence of depressive symptoms associated to MDD was made according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders fourth edition) and ICD-10 (International Statistical Classification of Disease and Related Health problems-10) base on clinical interviews.
(a) Clinical characteristics of HCV patients | ||
---|---|---|
Depression (−) | Depression (+) | |
All subjects | 30 (male: 20; female:10) | 19 (male: 12; female: 7) |
Age | 54.33 ± 2.06 | 54.0 ± 2.29 |
HCV genotype 1b | 24 (80%) | 15 (78.9%) |
HCV genotype 2a | 4 (13.3%) | 3 (15.8%) |
HCV genotype 2b | 2 (6.7%) | 1 (5.3%) |
AST | 59.43 ± 5.09 | 57.47 ± 6.45 |
ALT | 82.68 ± 11.36 | 69.56 ± 8.65 |
“Depression (−)”: HCV patients without depression, “Depression (+)”: HCV patients with depression following IFN-α therapy [47]. HCV, hepatitis C virus; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
(b) The time points of blood sampling | |||||
---|---|---|---|---|---|
Time points | Depression (−) (mean ± SEM) | Depression (+) (mean ± SEM) | t | df | p value |
(a) Before the onset of therapy | 1–35 d (6.3 ± 1.8 d) | 0–22 d (6.7 ± 1.3 d) | 0.230 | 48 | 0.819 |
(b) 2 w after the onset of therapy | 13–15 d (13.8 ± 0.1 d) | 12–15 d (13.6 ± 0.2 d) | 0.513 | 61 | 0.610 |
(c) 4 w after the onset of therapy | 25–30 d (27.9 ± 0.1 d) | 25–29 d (27.6 ± 0.3 d) | 0.952 | 40 | 0.347 |
(d) The period of therapy | 167–343 d (252.0 ± 15.7 d) | 54–337 d (183.4 ± 22.0 d*) | 2.592 | 46 | 0.013 |
Clinical information for HCV patients undergoing IFN-α therapy.
p<0.05 versus Depression (−) [47].
For all HCV patients, blood was collected before the onset of IFN-α therapy, as well as 2 and 4 weeks after the onset of therapy, and after the end or cessation of therapy. See Figure 3a for a detailed blood sampling schedule.
For all HCV patients, blood was collected before the onset of IFN-α therapy as well as 2 and 4 weeks after initiation of treatment. There was a no significant time difference for blood sampling between depression (−) and (+) patients (Table 1b and Figure 3).
Changes in the levels of serum TRP and its metabolites in HCV patients receiving IFN-α therapy. Original data from Ref. [47]. (a) Schematic depiction of the collection schedule for blood sampling from depression (−) and depression (+) HCV patients. The range of time points and average collection time point (a−d) per group are listed in Table 1b. (b) Serum TRP, KYN, KA, and 3-HK concentrations in HCV patients at 2 and 4 weeks after the onset of therapy, expressed as a percentage of the concentration before IFN-α therapy. (c) Serum KYN/TRP and 3-HK/KA ratios in HCV patients are shown as a percentage of values before IFN-α therapy. Rectangles indicate non-depressive HCV patients [Depression (−)] and circles indicate HCV patients with depressive symptoms [Depression (+)]. Each data point represents the mean ± SEM of values obtained from n = 30 depression (−) patients and n = 19 depression (+) patients. *p<0.05, ***p<0.001 versus before the onset of IFN-α therapy, #p<0.05, ##p<0.01 versus depression (−) patients. Detailed statistical analyses are shown in Table 2 [47].
Previous studies suggested that IDO1-mediated TRP metabolism could be implicated in the development of depression, as a side effect of IFN-α therapy in HCV patients. We also found that HCV patients showed decreased TRP and increased KYN concentrations without any changes in KA, AA, and 3-HAA concentrations during IFN-α therapy (Figure 3b and Table 2a). Furthermore, depression (+) patients presented a higher increase in 3-HK concentration compared to depression (−) patients during treatment (Table 2a). Ogawa et al. recently showed that plasma TRP concentration was significantly decreased in MDD patients compared to healthy controls [37]. Teraishi et al. also demonstrated increased KYN metabolites along the TRP-KYN-QUIN pathway, but not the KYN-KA pathway, in MDD patients [38]. Our results showed that the level of 3-HK in the serum significantly increased in depression (+) patients are consistent with these findings. We also investigated the ratios of 3-HK/KA (reflecting neurotoxic indices) [39, 40] and KYN/TRP (reflecting IDO1 activity) in depression (−) and depression (+) HCV patients during IFN-α treatment (Figure 3c and Table 2b). The ratios of KYN/TRP and 3-HK/KA in both groups increased during treatment. However, in depression (+) patients, the ratios of KYN/TRP and 3-HK/KA increased much larger in depression (−) patients during treatment (Table 2b). In these patients, the serum KYN/TRP and 3-HK/KA ratios increased more at the diagnosis of depression, but at 70.3 ± 9.1 days post therapy, they returned to the same levels as before onset of the therapy (data not shown). The severity of depression was not assessed during treatment, using neither the MADRS nor Hamilton Depressing Rating Scale. Therefore, we could not clearly show the direct association between the aggravation of depressive symptoms and changes in TRP metabolites. However, our results suggest that HCV patients with a high sensitivity for IDO1 activation by IFNs are highly susceptible to the depression-related side effects of IFN-α treatment.
(a) Changes in the levels of serum TRP and its metabolites | |||||
---|---|---|---|---|---|
% of value before IFN-α therapy | t | df | p value | ||
Depression (−) | Depression (+) | ||||
2 w after onset of therapy | |||||
TRP | 95.4 ± 2.93 | 100.5 ± 3.98 | 0.965 | 40 | 0.340 |
KYN | 108.6 ± 4.77 | 118.1 ± 4.24* | 1.200 | 39 | 0.237 |
3-HK | 117.0 ± 7.13 | 152.6 ± 10.4***, ## | 2.886 | 38 | 0.006 |
KA | 97.4 ± 5.51 | 95.9 ± 7.13 | 0.136 | 38 | 0.892 |
AA | 119.9 ± 7.42 | 115.5 ± 7.11 | 0.381 | 41 | 0.706 |
3-HAA | 102.9 ± 6.53 | 121.8 ± 12.6 | 1.452 | 37 | 0.155 |
4 w after onset of therapy | |||||
TRP | 92.0 ± 2.55 | 93.3 ± 6.49 | 0.213 | 39 | 0.833 |
KYN | 104.8 ± 4.38 | 114.4 ± 6.38 | 1.204 | 39 | 0.236 |
3-HK | 123.0 ± 9.01 | 155.0 ± 11.5*** | 2.005 | 36 | 0.053 |
KA | 91.9 ± 5.12 | 88.8 ± 6.98 | 0.341 | 40 | 0.735 |
AA | 107.5 ± 5.32 | 103.6 ± 11.3 | 0.361 | 40 | 0.720 |
3-HAA | 101.9 ± 6.52 | 104.5 ± 14.8 | 0.182 | 36 | 0.857 |
Percent value of serum TRP, KYN, 3-HK, KA, AA, and 3-HAA concentrations in HCV patients at 2 and 4 weeks after the onset of therapy, compared to the concentration (100%) before IFN-α therapy. In the clinical samples, some metabolites were difficult to separate clearly by HPLC. Therefore, the degree of freedom (df) values differ by the measured molecules. “Depression (−)”: HCV patients without depression, “Depression (+)”: HCV patients with depression.
(b) Changes in serum KYN/TRP and 3-HK/KA ratios | |||||
---|---|---|---|---|---|
% of value before IFN-α therapy | t | df | p value | ||
Depression (−) | Depression (+) | ||||
2 w after onset of therapy | |||||
KYN/TRP | 115.6 ± 4.55 | 114.1 ± 5.95 | 0.198 | 42 | 0.844 |
3-HK/KA | 129.1 ± 9.52 | 144.0±9.06* | 1.036 | 39 | 0.308 |
4 w after onset of therapy | |||||
KYN/TRP | 115.7 ± 5.69 | 138.3±8.84*,# | 2.094 | 35 | 0.044 |
3-HK/KA | 129.6 ± 8.67 | 171.1 ± 18.6***,# | 2.325 | 35 | 0.026 |
Changes in TRP-KYN pathway in HCV patients undergoing IFN-α therapy.
Serum KYN/TRP reflects IDO1 activity, and 3-HK/KA reflects neurotoxic indices. Both ratios in HCV patients were shown as % of value compared to the value (100%) before IFN-α therapy, at 2 and 4 weeks after the onset of therapy.
We hypothesized that the high induction of IDO1 and the imbalance of TRP metabolites induced by IFNs in humans may be related to psychiatric side effects, such as depression. Previous studies have shown that all three IFNs (IFN-α, -β, and -γ) induce strong IDO1 activity in human peripheral blood mononuclear cells [41, 42]. In contrast, in mouse, IDO1 is induced more markedly by IFN-γ than IFN-α, which has only a weak direct IDO1-stimulatory effect. Therefore, we investigated whether IDO1 activity induced by Ifn-γ gene transfer impaired behavior in mice.
To conduct this experiment, for murine Ifn-γ gene transfer, the plasmid pCpG-Muγ was constructed by inserting a BglII/NheI murine Ifn-γ cDNA fragment into the BglII/NheI site of the pCpG-mcs vector (Figure 4a). The prepared plasmid pCpG-Muγ was dissolved in normal saline and injected into the tail veins of the mice for over 5 s on day 0. The injection volume was approximately 9% (v/w) of body weight. To eliminate the possibility of tissue damage or inflammation by the hydrodynamic injection, a control plasmid, which was the empty vector without the Ifn-γ gene (pCpG-mcs), was injected (0.05 pmol/mouse; IFN-γ transfected (−) mice). A previous study demonstrated that sustained IFN-γ concentrations were observed in mice receiving pCpG-Muγ at a dose of 0.2 pmol/mouse and more than 1000 pg/mL of IFN-γ was detected in the serum from 6 to 31 days after injection of pCpG-Muγ [43]. We also confirmed that the injected plasmid, pCpG-Muγ (IFN-γ transfected (+) mice) significantly increased IDO1 activity in the frontal cortex over a dose of 0.05 pmol/mouse compared to IFN-γ transfected (−) mice (Figure 4c). Therefore, the plasmid dose was fixed at 0.05 pmol/mouse for subsequent experiments, which corresponded to 0.10–0.12 μg of DNA/mouse.
Ifn-γ gene transfer. Original data from Ref. [47]. (a) Schematic depiction of the pCpG-Muγ plasmid construct (InvivoGen, San Diego, CA). (b) Schematic depiction of the time schedule for animal experiments. (c) Increase of IDO1 activity in the frontal cortex of mice 28 days after Ifn-γ gene transfer [47]. βGlo MAR, β-globin matrix attachment region; mCMV enh, mouse cytomegalovirus enhancer; hEF1 prom, human elongation factor1 promoter; I140, synthetic 5′UTR containing an intron 140; MCS, multi cloning site; SV40 pAn, Simianvirus 40 polyadenylation; IFN-β S/MAR, interferon β gene scaffold/matrix attachment region; EM2K, CpG-free version of the bacterial EM7 promoter; Zeo, Zeocin; R6K ori, R6K origin.
In order to clarify whether the activation of IDO1 by IFN-γ-affected behaviors, three tests, open-field test (OFT), the Y-maze test, and forced swimming test (FST), were performed in mice. Mice were transfected with either a pCpG-mcs plasmid (control vector) that did not contain the Ifn-γ gene [IFN-γ-transfected (−) mice] or a pCpG-Muγ plasmid that long-lasting expressed Ifn-γ [IFN-γ transfected (+) mice]. No significant differences in locomotor activity of the OFT was observed between IFN-γ transfected (−) and (+) mice. Similarly, in the Y-maze test, no significant differences in the alternation behavior were detected between the two groups of mice. However, in the FST, immobility time was significantly longer in IFN-γ-transfected (+) mice (Figure 5a). Our findings strongly suggest that IDO1 induction by IFN-γ is a critical factor in depression-like behaviors but not in short-term memory or locomotor activity in mice.
The effect of chronic Ifn-γ gene expression on the TRP-KYN pathway and depression-like behavior in mice. Original data from Ref. [47]. (a) Behavioral changes in mice 28 days after Ifn-γ gene transfer. Open field test shows locomotor activity of mice in a novel environment. Y-maze test shows short-term memory. Forced swim test shows depression-like behavior. Immobility time was significantly increased in IFN-γ-transfected (+) mice, compared to IFN-γ-transfected (−) mice. The open bar shows IFN-γ-transfected (−) mice, and the closed bar shows IFN-γ-transfected (+) mice. Each column represents the mean ± SEM (n = 9–16). *p <0.05 versus IFN-γ-transfected (−) mice. (b) (c) Changes in the levels of TRP and its metabolites in the serum and frontal cortex of mice after Ifn-γ gene transfer. TRP-KYN metabolite concentrations were determined in the serum (b) and the frontal cortex (c) of mice 35 days after Ifn-γ-gene transfer. The open bar shows IFN-γ-transfected (−) mice, and the closed bar shows IFN-γ-transfected (+) mice. Each column represents the mean ± SEM (n = 15–20). **p<0.01, ***p<0.001 versus IFN-γ-transfected (−) mice [47].
In order to further elucidate the relationship between the IDO1-induced KYN pathway and the development of depression-like behavior in mice transfected with the pCpG-Muγ plasmid, we measured TRP metabolites in the serum and frontal cortex of these mice.
The serum and the frontal cortex were corrected from mice immediately following behavioral testing to determine the levels of TRP, KYN, KA, 3-HK, 3-HAA, and AA (Figure 5b and c). The concentration of serum TRP was significantly decreased in IFN-γ transfected (+) mice compared to IFN-γ-transfected (−) mice. In contrast, the levels of serum KYN and 3-HK were significantly increased in the IFN-γ-transfected (+) mice (Figure 5b). In the frontal cortex, IFN-γ transfected (+) mice had significantly higher KYN and 3-HK levels than the IFN-γ-transfected (−) mice. The TRP and KA levels in the frontal cortex tended to be lower in the IFN-γ-transfected (+) mice (Figure 5c). The activation of IDO1 by Ifn-γ gene transfer significantly modified the levels of TRP and its metabolites not only in the serum, but also in the frontal cortex of mice. These results suggest that an alternative explanation for the participation of IDO1 in IFN-γ-induced depression-like behavior is the generation of neuroactive TRP metabolites. This interpretation is consistent with our clinical data and previous studies by O’Connor et al. and Wichers et al. [32, 35].
Additionally, we evaluated the role of IDO1 in the development of depression-like behavior after Ifn-γ gene transfer using Ido1 gene knockout (KO) mice, and determined the levels of TRP metabolites in the frontal cortex.
The increase in time spent in an immobile posture in the Ifn-γ-transfected (+)/wild type mice was significantly improved in Ido1 KO mice (Figure 6a). In wild type mice, Ifn-γ gene transfer significantly increased the concentrations of KYN and 3-HK in the frontal cortex by 4.7- and 2.5-fold, respectively. In contrast, Ido1 KO mice withdrew these changes in Ifn-γ gene transfer mice (Figure 6b). The levels of KYN and 3-HK in the frontal cortex after Ifn-γ gene transfer were considerably lower in Ido1 KO mice than in wild type mice. Even though we cannot exclude the possibility that genetic deficient in Ido1 and the resulting modifications in TRP metabolites could influence other behavioral tests, our results clearly demonstrate that Ido1 KO mice do not show depression-like behavior and do not intensify TRP metabolites after Ifn-γ gene transfer.
The effects of Ido1 gene-deficiency on depression-like behavior, changes in TRP metabolism, 5-HT, and its turnover in the frontal cortex of mice following chronic Ifn-γ gene expression. Original data from Ref. [47]. (a) Abnormal behavior in a forced swimming test after Ifn-γ gene transfer in mice was improved in Ido1 gene deficient mice. The Y axis shows the percent value of immobility time in IFN-γ-transfected (+) mice, compared to the time (100%) in IFN-γ-transfected (−) mice (n = 8–15). (b) The level of TRP metabolites in the frontal cortex of mice 35 days after Ifn-γ-gene transfer (n = 6–15). (c) The amount of 5-HT, 5-HIAA, and 5-HIAA/5-HT ratio as an index of serotonin turnover in the frontal cortex of mice 35 days after Ifn-γ-gene transfer (n = 6–15). The open bar represents wild type and the closed bar, Ido1 gene deficient mice. IFN-γ-transfected (−) mice were injected with the control plasmid (pCpG-mcs), and IFN-γ-transfected (+) mice were injected with the IFN-γ-expressing pCpG-Muγ plasmid. Each column represents the mean ± SEM. *p<0.05, ***p<0.001 versus IFN-γ-transfected (−) wild type mice, #p<0.05, ##p<0.01, ###p<0.001 versus IFN-γ-transfected (+) wild type mice [47].
Other studies have emphasized that the 5-HT pathway is also relevant to depression. In a clinical study, it has been shown that levels of TRP and 5-hydroxytryptophan, a precursor of 5-HT, were significantly decreased from their baseline levels in the serum of HCV patients during IFN-α therapy [44]. Thus, we speculate that biological mechanisms underlying the IFN-α treatment induced-depressive symptoms are linked not only to the activated IDO1 and KYN pathway but also to a dysfunction of the 5-HT system. To clarify on the basis of the neurotransmitter changes in depression-like behavior after Ifn-γ gene transfer, we measured the concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex of wild type and Ido1 KO mice (Figure 6c). We showed that Ifn-γ gene transfer produced a trend toward increased 5-HIAA levels in wild type mice but not in Ido1 KO mice. These results indicated that Ifn-γ gene transfer induced a potential increase in IDO1-induced 5-HT turnover. A raised 5-HT turnover suggests a process by which the availability of 5-HT to be released by neurons is decreased to compensate for neuronal dysfunction associated with depression-like behavior promoted by Ifn-γ gene transfer. Correspondingly, previous clinical studies have shown that brain 5-HT turnover is significantly increased in MDD patients without medication and decreased following selective serotonin reuptake inhibitors (SSRI) therapy [45, 46].
Taken together, an alternative interpretation for the involvement of IDO1 in IFN-γ-induced depression-like behavior may be that depression is related to not only the generation of neuroactive TRP metabolites but also to the alteration of serotoninergic neurotransmission.
The levels of TRP metabolites in the serum of HCV patients changed significantly. In particular, the increase in serum 3-HK concentration in depressive HCV patients was much larger than that in HCV patients without depressive symptoms. The ratios of serum KYN/TRP, reflecting IDO1 activity, and 3-HK/KA were increased in depressive and non-depressed HCV patients with therapy. However, the increase in serum KYN/TRP and 3-HK/KA ratios in depressive patients was much higher than that of non-depressive HCV patients. When the Ifn-γ gene was transfected into normal mice, depression-like behavior significantly increased. Additionally, Ifn-γ gene transfer to mice induced dramatic changes in TRP metabolite concentrations in the serum and the prefrontal cortex. On the other hand, genetic deletion of Ido1 abrogated the enhanced depression-like behavior after Ifn-γ gene transfer. In conclusion, our results clearly show that IDO1 is a critical molecular regulator of the depressive pathology induced as a side effect of interferon therapy. Moreover, the depressive symptoms are induced via increases in degradation of TRP and neuroactive metabolites along the KYN pathway, which finally changes in the alternation of 5-HT turnover. Our findings suggest that inflammatory pathways that lead to the activation of IDO1 may be a novel therapeutic target in patients suffering from inflammation-associated depression, for example, HCV or cancer therapy. Our results also suggest the monitoring of TRP-KYN metabolites during immunotherapy might assist in predicting the onset risk of depression as a side effect in these patients. However, further insight into the role of each downstream KYN pathway metabolite in the pathological process is needed to understand, and to clarify the relationship with complex neurotransmitters.
This work was supported by Grant-in Aid for Scientific Research of YM (26860368 and 16K08948).
Unsubscribe unsuccessful, no matching records found in our database.
",metaTitle:"Unsubscribe Unsuccessful",metaDescription:"Unsubscribe unsuccessful, no matching records found in our database.",metaKeywords:null,canonicalURL:"/page/unsubscribe-unsuccessful",contentRaw:'[{"type":"htmlEditorComponent","content":""}]'},components:[{type:"htmlEditorComponent",content:""}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5774},{group:"region",caption:"Middle and South America",value:2,count:5240},{group:"region",caption:"Africa",value:3,count:1721},{group:"region",caption:"Asia",value:4,count:10411},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15812}],offset:12,limit:12,total:118381},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish",topicId:"11,10,12"},books:[{type:"book",id:"10654",title:"Brain-Computer Interface",subtitle:null,isOpenForSubmission:!0,hash:"a5308884068cc53ed31c6baba756857f",slug:null,bookSignature:"Dr. Vahid Asadpour",coverURL:"https://cdn.intechopen.com/books/images_new/10654.jpg",editedByType:null,editors:[{id:"165328",title:"Dr.",name:"Vahid",surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10765",title:"Environmental Management",subtitle:null,isOpenForSubmission:!0,hash:"e5ba02fedd7c87f0ab66414f3b07de0c",slug:null,bookSignature:"Dr. John P. Tiefenbacher",coverURL:"https://cdn.intechopen.com/books/images_new/10765.jpg",editedByType:null,editors:[{id:"73876",title:"Dr.",name:"John P.",surname:"Tiefenbacher",slug:"john-p.-tiefenbacher",fullName:"John P. Tiefenbacher"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10567",title:"Uncertainty Management in Engineering - Topics in Pollution Prevention and Controls",subtitle:null,isOpenForSubmission:!0,hash:"4990db602d31f1848c590dbfe97b6409",slug:null,bookSignature:"Prof. Rehab O. Abdel Rahman and Dr. Yung-Tse Hung",coverURL:"https://cdn.intechopen.com/books/images_new/10567.jpg",editedByType:null,editors:[{id:"92718",title:"Prof.",name:"Rehab",surname:"Abdel Rahman",slug:"rehab-abdel-rahman",fullName:"Rehab Abdel Rahman"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10568",title:"Hysteresis in Engineering",subtitle:null,isOpenForSubmission:!0,hash:"6482387993b3cebffafe856a916c44ce",slug:null,bookSignature:"Dr. Giuseppe Viola",coverURL:"https://cdn.intechopen.com/books/images_new/10568.jpg",editedByType:null,editors:[{id:"173586",title:"Dr.",name:"Giuseppe",surname:"Viola",slug:"giuseppe-viola",fullName:"Giuseppe Viola"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8969",title:"Deserts and Desertification",subtitle:null,isOpenForSubmission:!0,hash:"4df95c7f295de7f6003e635d9a309fe9",slug:null,bookSignature:"Dr. Yajuan Zhu, Dr. Qinghong Luo and Dr. Yuguo Liu",coverURL:"https://cdn.intechopen.com/books/images_new/8969.jpg",editedByType:null,editors:[{id:"180427",title:"Dr.",name:"Yajuan",surname:"Zhu",slug:"yajuan-zhu",fullName:"Yajuan Zhu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10584",title:"Engineered Wood Products for Construction",subtitle:null,isOpenForSubmission:!0,hash:"421757c56a3735986055250821275a51",slug:null,bookSignature:"Dr. Meng Gong",coverURL:"https://cdn.intechopen.com/books/images_new/10584.jpg",editedByType:null,editors:[{id:"274242",title:"Dr.",name:"Meng",surname:"Gong",slug:"meng-gong",fullName:"Meng Gong"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10769",title:"Supercapacitors",subtitle:null,isOpenForSubmission:!0,hash:"dda2f53b2c9ee308fe5f3e0d1638ff5c",slug:null,bookSignature:"Associate Prof. Daisuke Tashima",coverURL:"https://cdn.intechopen.com/books/images_new/10769.jpg",editedByType:null,editors:[{id:"254915",title:"Associate Prof.",name:"Daisuke",surname:"Tashima",slug:"daisuke-tashima",fullName:"Daisuke Tashima"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10370",title:"Advances in Fundamental and Applied Research on Spatial Audio",subtitle:null,isOpenForSubmission:!0,hash:"f16232a481c08a05cc191ac64cf2c69e",slug:null,bookSignature:"Dr. Brian FG Katz and Dr. Piotr Majdak",coverURL:"https://cdn.intechopen.com/books/images_new/10370.jpg",editedByType:null,editors:[{id:"278731",title:"Dr.",name:"Brian FG",surname:"Katz",slug:"brian-fg-katz",fullName:"Brian FG Katz"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10754",title:"Global Warming and Climate Change",subtitle:null,isOpenForSubmission:!0,hash:"8994a915a306910a01cbe2027aa2139b",slug:null,bookSignature:"Dr. Stuart Arthur Harris",coverURL:"https://cdn.intechopen.com/books/images_new/10754.jpg",editedByType:null,editors:[{id:"12539",title:"Dr.",name:"Stuart",surname:"Harris",slug:"stuart-harris",fullName:"Stuart Harris"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10683",title:"Hydropower",subtitle:null,isOpenForSubmission:!0,hash:"7ce7ad8768bd2cad155470fe1fd883f4",slug:null,bookSignature:"Dr. Yizi Shang, Dr. Ling Shang and Dr. Xiaofei Li",coverURL:"https://cdn.intechopen.com/books/images_new/10683.jpg",editedByType:null,editors:[{id:"349630",title:"Dr.",name:"Yizi",surname:"Shang",slug:"yizi-shang",fullName:"Yizi Shang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10681",title:"Biodegradation",subtitle:null,isOpenForSubmission:!0,hash:"9a6e10e02788092872fd249436898e97",slug:null,bookSignature:"Ph.D. Kassio Ferreira Mendes, Dr. Rodrigo Nogueira de Sousa and Dr. Kamila Cabral Mielke",coverURL:"https://cdn.intechopen.com/books/images_new/10681.jpg",editedByType:null,editors:[{id:"197720",title:"Ph.D.",name:"Kassio",surname:"Ferreira Mendes",slug:"kassio-ferreira-mendes",fullName:"Kassio Ferreira Mendes"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10763",title:"Biodiversity of Ecosystems",subtitle:null,isOpenForSubmission:!0,hash:"c96b42d4539957c58dfc2eb8fd9ffc21",slug:null,bookSignature:"Dr. Levente Hufnagel",coverURL:"https://cdn.intechopen.com/books/images_new/10763.jpg",editedByType:null,editors:[{id:"10864",title:"Dr.",name:"Levente",surname:"Hufnagel",slug:"levente-hufnagel",fullName:"Levente Hufnagel"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:19},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:5},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:9},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:21},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:6},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:26},{group:"topic",caption:"Neuroscience",value:18,count:2},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:4},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:12,limit:12,total:30},popularBooks:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5252},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editedByType:"Edited by",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editedByType:"Edited by",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editedByType:"Edited by",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editedByType:"Edited by",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9669",title:"Recent Advances in Rice Research",subtitle:null,isOpenForSubmission:!1,hash:"12b06cc73e89af1e104399321cc16a75",slug:"recent-advances-in-rice-research",bookSignature:"Mahmood-ur- Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9669.jpg",editedByType:"Edited by",editors:[{id:"185476",title:"Dr.",name:"Mahmood-Ur-",middleName:null,surname:"Rahman Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-Ur- Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"540",title:"Wireless Communication Network",slug:"communications-and-security-wireless-communication-network",parent:{title:"Communications and Security",slug:"communications-and-security"},numberOfBooks:10,numberOfAuthorsAndEditors:266,numberOfWosCitations:475,numberOfCrossrefCitations:263,numberOfDimensionsCitations:522,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"communications-and-security-wireless-communication-network",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"9219",title:"Recent Trends in Communication Networks",subtitle:null,isOpenForSubmission:!1,hash:"80b5339ac7ae4b7a91fd4e71b4d468e5",slug:"recent-trends-in-communication-networks",bookSignature:"Pinaki Mitra",coverURL:"https://cdn.intechopen.com/books/images_new/9219.jpg",editedByType:"Edited by",editors:[{id:"89103",title:"Prof.",name:"Pinaki",middleName:null,surname:"Mitra",slug:"pinaki-mitra",fullName:"Pinaki Mitra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7322",title:"Wireless Mesh Networks",subtitle:"Security, Architectures and Protocols",isOpenForSubmission:!1,hash:"db5ab870ec11f9d4d1ebb54c7dd6e2bf",slug:"wireless-mesh-networks-security-architectures-and-protocols",bookSignature:"Mutamed Khatib and Samer Alsadi",coverURL:"https://cdn.intechopen.com/books/images_new/7322.jpg",editedByType:"Edited by",editors:[{id:"22273",title:"Dr.",name:"Mutamed",middleName:null,surname:"Khatib",slug:"mutamed-khatib",fullName:"Mutamed Khatib"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8662",title:"Data Service Outsourcing and Privacy Protection in Mobile Internet",subtitle:null,isOpenForSubmission:!1,hash:"697eadc7a3390023bb43d1d2406f0ebb",slug:"data-service-outsourcing-and-privacy-protection-in-mobile-internet",bookSignature:"Zhen Qin, Erqiang Zhou, Yi Ding, Yang Zhao, Fuhu Deng and Hu Xiong",coverURL:"https://cdn.intechopen.com/books/images_new/8662.jpg",editedByType:"Authored by",editors:[{id:"101193",title:"Dr.",name:"Hu",middleName:null,surname:"Xiong",slug:"hu-xiong",fullName:"Hu Xiong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"3",chapterContentType:"chapter",authoredCaption:"Authored by"}},{type:"book",id:"3139",title:"Wireless Ad-Hoc Networks",subtitle:null,isOpenForSubmission:!1,hash:"5a8ce0920ae4a8c48e38a9bc60684aa1",slug:"wireless-ad-hoc-networks",bookSignature:"Hongbo Zhou",coverURL:"https://cdn.intechopen.com/books/images_new/3139.jpg",editedByType:"Edited by",editors:[{id:"154490",title:"Dr.",name:"Hongbo",middleName:null,surname:"Zhou",slug:"hongbo-zhou",fullName:"Hongbo Zhou"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1938",title:"Advanced Wireless LAN",subtitle:null,isOpenForSubmission:!1,hash:"e4d4c069bc97e5c0ad97e60e023b6827",slug:"advanced-wireless-lan",bookSignature:"Song Guo",coverURL:"https://cdn.intechopen.com/books/images_new/1938.jpg",editedByType:"Edited by",editors:[{id:"15566",title:"Dr.",name:"Song",middleName:null,surname:"Guo",slug:"song-guo",fullName:"Song Guo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"97",title:"Cellular Networks",subtitle:"Positioning, Performance Analysis, Reliability",isOpenForSubmission:!1,hash:"ca45ba51c623c9aef3c0d25772413039",slug:"cellular-networks-positioning-performance-analysis-reliability",bookSignature:"Agassi Melikov",coverURL:"https://cdn.intechopen.com/books/images_new/97.jpg",editedByType:"Edited by",editors:[{id:"23032",title:"Dr.",name:"Agassi",middleName:null,surname:"Melikov",slug:"agassi-melikov",fullName:"Agassi Melikov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"137",title:"Sustainable Wireless Sensor Networks",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"sustainable-wireless-sensor-networks",bookSignature:"Winston Seah and Yen Kheng Tan",coverURL:"https://cdn.intechopen.com/books/images_new/137.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"135",title:"Wireless Sensor Networks",subtitle:"Application - Centric Design",isOpenForSubmission:!1,hash:null,slug:"wireless-sensor-networks-application-centric-design",bookSignature:"Geoff V Merrett and Yen Kheng Tan",coverURL:"https://cdn.intechopen.com/books/images_new/135.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"136",title:"Smart Wireless Sensor Networks",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"smart-wireless-sensor-networks",bookSignature:"Hoang Duc Chinh and Yen Kheng Tan",coverURL:"https://cdn.intechopen.com/books/images_new/136.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3628",title:"Mobile and Wireless Communications",subtitle:"Network Layer and Circuit Level Design",isOpenForSubmission:!1,hash:null,slug:"mobile-and-wireless-communications-network-layer-and-circuit-level-design",bookSignature:"Salma Ait Fares and Fumiyuki Adachi",coverURL:"https://cdn.intechopen.com/books/images_new/3628.jpg",editedByType:"Edited by",editors:[{id:"3125",title:"Dr.",name:"Salma",middleName:null,surname:"Ait Fares",slug:"salma-ait-fares",fullName:"Salma Ait Fares"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:10,mostCitedChapters:[{id:"9002",doi:"10.5772/7698",title:"Terrestrial Free-Space Optical Communications",slug:"terrestrial-free-space-optical-communications",totalDownloads:7305,totalCrossrefCites:8,totalDimensionsCites:73,book:{slug:"mobile-and-wireless-communications-network-layer-and-circuit-level-design",title:"Mobile and Wireless Communications",fullTitle:"Mobile and Wireless Communications Network Layer and Circuit Level Design"},signatures:"Ghassemlooy Z. and Popoola W. O.",authors:null},{id:"12472",doi:"10.5772/13802",title:"Monitoring of Human Movements for Fall Detection and Activities Recognition in Elderly Care Using Wireless Sensor Network: a Survey",slug:"monitoring-of-human-movements-for-fall-detection-and-activities-recognition-in-elderly-care-using-wi",totalDownloads:14793,totalCrossrefCites:36,totalDimensionsCites:54,book:{slug:"wireless-sensor-networks-application-centric-design",title:"Wireless Sensor Networks",fullTitle:"Wireless Sensor Networks: Application - Centric Design"},signatures:"Stefano Abbate, Marco Avvenuti, Paolo Corsini, Janet Light and Alessio Vecchio",authors:[{id:"14025",title:"MSc.",name:"Stefano",middleName:null,surname:"Abbate",slug:"stefano-abbate",fullName:"Stefano Abbate"},{id:"15973",title:"Prof.",name:"Marco",middleName:null,surname:"Avvenuti",slug:"marco-avvenuti",fullName:"Marco Avvenuti"},{id:"15974",title:"Prof.",name:"Paolo",middleName:null,surname:"Corsini",slug:"paolo-corsini",fullName:"Paolo Corsini"},{id:"15975",title:"PhD.",name:"Alessio",middleName:null,surname:"Vecchio",slug:"alessio-vecchio",fullName:"Alessio Vecchio"},{id:"15976",title:"Prof.",name:"Janet",middleName:null,surname:"Light",slug:"janet-light",fullName:"Janet Light"}]},{id:"12418",doi:"10.5772/13062",title:"Review of Energy Harvesting Technologies for Sustainable WSN",slug:"review-of-energy-harvesting-technologies-for-sustainable-wsn",totalDownloads:3882,totalCrossrefCites:2,totalDimensionsCites:49,book:{slug:"sustainable-wireless-sensor-networks",title:"Sustainable Wireless Sensor Networks",fullTitle:"Sustainable Wireless Sensor Networks"},signatures:"Yen Kheng Tan and Sanjib Kumar Panda",authors:[{id:"15547",title:"Dr.",name:"Sanjib Kumar",middleName:null,surname:"Panda",slug:"sanjib-kumar-panda",fullName:"Sanjib Kumar Panda"},{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}]}],mostDownloadedChaptersLast30Days:[{id:"72470",title:"A Mobile Ad Hoc Network Routing Protocols: A Comparative Study",slug:"a-mobile-ad-hoc-network-routing-protocols-a-comparative-study",totalDownloads:419,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"recent-trends-in-communication-networks",title:"Recent Trends in Communication Networks",fullTitle:"Recent Trends in Communication Networks"},signatures:"Alagan Ramasamy Rajeswari",authors:[{id:"320070",title:"Dr.",name:"Rajeswari",middleName:null,surname:"Alagan Ramasamy",slug:"rajeswari-alagan-ramasamy",fullName:"Rajeswari Alagan Ramasamy"}]},{id:"12472",title:"Monitoring of Human Movements for Fall Detection and Activities Recognition in Elderly Care Using Wireless Sensor Network: a Survey",slug:"monitoring-of-human-movements-for-fall-detection-and-activities-recognition-in-elderly-care-using-wi",totalDownloads:14791,totalCrossrefCites:36,totalDimensionsCites:54,book:{slug:"wireless-sensor-networks-application-centric-design",title:"Wireless Sensor Networks",fullTitle:"Wireless Sensor Networks: Application - Centric Design"},signatures:"Stefano Abbate, Marco Avvenuti, Paolo Corsini, Janet Light and Alessio Vecchio",authors:[{id:"14025",title:"MSc.",name:"Stefano",middleName:null,surname:"Abbate",slug:"stefano-abbate",fullName:"Stefano Abbate"},{id:"15973",title:"Prof.",name:"Marco",middleName:null,surname:"Avvenuti",slug:"marco-avvenuti",fullName:"Marco Avvenuti"},{id:"15974",title:"Prof.",name:"Paolo",middleName:null,surname:"Corsini",slug:"paolo-corsini",fullName:"Paolo Corsini"},{id:"15975",title:"PhD.",name:"Alessio",middleName:null,surname:"Vecchio",slug:"alessio-vecchio",fullName:"Alessio Vecchio"},{id:"15976",title:"Prof.",name:"Janet",middleName:null,surname:"Light",slug:"janet-light",fullName:"Janet Light"}]},{id:"14756",title:"Call-Level Performance Sensitivity in Cellular Networks",slug:"call-level-performance-sensitivity-in-cellular-networks",totalDownloads:1586,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"cellular-networks-positioning-performance-analysis-reliability",title:"Cellular Networks",fullTitle:"Cellular Networks - Positioning, Performance Analysis, Reliability"},signatures:"Felipe A. Cruz-Pérez, Genaro Hernández-Valdez and Andrés Rico-Páez",authors:[{id:"19751",title:"Mr.",name:"Genaro",middleName:null,surname:"Hernández-Valdez",slug:"genaro-hernandez-valdez",fullName:"Genaro Hernández-Valdez"},{id:"20630",title:"Dr.",name:"Felipe A.",middleName:null,surname:"Cruz Pérez",slug:"felipe-a.-cruz-perez",fullName:"Felipe A. Cruz Pérez"},{id:"22692",title:"Mr.",name:"Andres",middleName:null,surname:"Rico-Paez",slug:"andres-rico-paez",fullName:"Andres Rico-Paez"}]},{id:"41427",title:"Reducing Routing Loops Under Link-State Routing in Wireless Mesh Networks",slug:"reducing-routing-loops-under-link-state-routing-in-wireless-mesh-networks",totalDownloads:1997,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"wireless-ad-hoc-networks",title:"Wireless Ad-Hoc Networks",fullTitle:"Wireless Ad-Hoc Networks"},signatures:"Takuya Yoshihiro",authors:[{id:"13453",title:"Dr.",name:"Takuya",middleName:null,surname:"Yoshihiro",slug:"takuya-yoshihiro",fullName:"Takuya Yoshihiro"}]},{id:"12464",title:"Wireless Sensor Networks - An Introduction",slug:"wireless-sensor-networks-an-introduction",totalDownloads:13105,totalCrossrefCites:17,totalDimensionsCites:29,book:{slug:"wireless-sensor-networks-application-centric-design",title:"Wireless Sensor Networks",fullTitle:"Wireless Sensor Networks: Application - Centric Design"},signatures:"Qinghua Wang and Ilangko Balasingham",authors:[{id:"13799",title:"Dr.",name:"Qinghua",middleName:null,surname:"Wang",slug:"qinghua-wang",fullName:"Qinghua Wang"},{id:"23809",title:"Prof.",name:"Ilangko",middleName:null,surname:"Balasingham",slug:"ilangko-balasingham",fullName:"Ilangko Balasingham"}]},{id:"12487",title:"Imaging in UWB Sensor Networks",slug:"imaging-in-uwb-sensor-networks",totalDownloads:2516,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"wireless-sensor-networks-application-centric-design",title:"Wireless Sensor Networks",fullTitle:"Wireless Sensor Networks: Application - Centric Design"},signatures:"Ole Hirsch, Rudolf Zetik and Reiner Thomä",authors:[{id:"14629",title:"Dr.",name:"Ole",middleName:null,surname:"Hirsch",slug:"ole-hirsch",fullName:"Ole Hirsch"},{id:"14630",title:"Dr.",name:"Rudolf",middleName:null,surname:"Zetik",slug:"rudolf-zetik",fullName:"Rudolf Zetik"},{id:"14632",title:"Prof.",name:"Reiner",middleName:null,surname:"Thomä",slug:"reiner-thoma",fullName:"Reiner Thomä"}]},{id:"70079",title:"MAC Aspects of Millimeter-Wave Cellular Networks",slug:"mac-aspects-of-millimeter-wave-cellular-networks",totalDownloads:259,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"wireless-mesh-networks-security-architectures-and-protocols",title:"Wireless Mesh Networks",fullTitle:"Wireless Mesh Networks - Security, Architectures and Protocols"},signatures:"Hossein S. Ghadikolaei",authors:null},{id:"12466",title:"Wildlife Assessment Using Wireless Sensor Networks",slug:"wildlife-assessment-using-wireless-sensor-networks",totalDownloads:2649,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"wireless-sensor-networks-application-centric-design",title:"Wireless Sensor Networks",fullTitle:"Wireless Sensor Networks: Application - Centric Design"},signatures:"Harry Gros-desormeaux, Philippe Hunel and Nicolas Vidot",authors:[{id:"15994",title:"Dr.",name:"Nicolas",middleName:null,surname:"Vidot",slug:"nicolas-vidot",fullName:"Nicolas Vidot"},{id:"15995",title:"Dr.",name:"Philippe",middleName:null,surname:"Hunel",slug:"philippe-hunel",fullName:"Philippe Hunel"},{id:"15996",title:"Dr.",name:"Harry",middleName:null,surname:"Gros-Desormeaux",slug:"harry-gros-desormeaux",fullName:"Harry Gros-Desormeaux"}]},{id:"12457",title:"Security of Wireless Sensor Networks: Current Status and Key Issues",slug:"security-of-wireless-sensor-networks-current-status-and-key-issues",totalDownloads:2401,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"smart-wireless-sensor-networks",title:"Smart Wireless Sensor Networks",fullTitle:"Smart Wireless Sensor Networks"},signatures:"Chun-ta Li",authors:[{id:"13973",title:"Dr.",name:"Chun-Ta",middleName:null,surname:"Li",slug:"chun-ta-li",fullName:"Chun-Ta Li"}]},{id:"41429",title:"Review of Autoconfiguration for MANETs",slug:"review-of-autoconfiguration-for-manets",totalDownloads:1924,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"wireless-ad-hoc-networks",title:"Wireless Ad-Hoc Networks",fullTitle:"Wireless Ad-Hoc Networks"},signatures:"Hongbo Zhou and Matt W. Mutka",authors:[{id:"154490",title:"Dr.",name:"Hongbo",middleName:null,surname:"Zhou",slug:"hongbo-zhou",fullName:"Hongbo Zhou"}]}],onlineFirstChaptersFilter:{topicSlug:"communications-and-security-wireless-communication-network",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/145154/hayley-dickinson",hash:"",query:{},params:{id:"145154",slug:"hayley-dickinson"},fullPath:"/profiles/145154/hayley-dickinson",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)}()