The complete family of gyro-device.
\r\n\tThe purpose of the book is to bring together the latest knowledge about genetic diversity by presenting the studies of some of the scientists who are engaged in development of new tools and ideas used to reveal genetic diversity, often from very different perspectives. The book should prove useful to students, researchers and experts in the area of biology, medicine and agriculture.
",isbn:"978-1-80356-945-1",printIsbn:"978-1-80356-944-4",pdfIsbn:"978-1-80356-946-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"0b1e679fcacdec2448603a66df71ccc7",bookSignature:"Prof. Mahmut Çalışkan and Dr. Sevcan Aydin",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11643.jpg",keywords:"PCR Based Methods, Protein Based Methods, Sequencing, Conservation of Genetic Resources, Natural Variation, Molecular Markers, Genetic Manipulation in Animals, Resistance to Disease, Genetic Manipulation in Plants, Use of Microorganisms in Biotechnology, Genetic Differentiation, Gene Therapy and Gene Editing",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2022",dateEndSecondStepPublish:"May 5th 2022",dateEndThirdStepPublish:"July 4th 2022",dateEndFourthStepPublish:"September 22nd 2022",dateEndFifthStepPublish:"November 21st 2022",remainingDaysToSecondStep:"14 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Professor of genetics and molecular biology and Head of Biotechnology division at İstanbul University in Turkey whose main research areas include plant molecular genetics, microbial biotechnology and characterization and biotechnological use of halophilic archaeal strains.",coeditorOneBiosketch:"Associate Professor of Biotechnology Division in Department of Biology at Istanbul University in Turkey whose main research areas include genetics, environmental biotechnology and bioengineering.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"51528",title:"Prof.",name:"Mahmut",middleName:null,surname:"Çalışkan",slug:"mahmut-caliskan",fullName:"Mahmut Çalışkan",profilePictureURL:"https://mts.intechopen.com/storage/users/51528/images/system/51528.png",biography:"Mahmut Çalışkan is a Professor of Genetics and Molecular Biology in the Department of Biology, Biotechnology Division, Istanbul University, Turkey. He obtained a BSc from Middle East Technical University, Ankara, and a Ph.D. from the University of Leeds, England. His main research areas include the role of germin gene products during early plant development, analysis of genetic variation, polymorphisms, and the characterization and biotechnological use of halophilic archaea.",institutionString:"Istanbul University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"8",institution:{name:"Istanbul University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:{id:"462767",title:"Dr.",name:"Sevcan",middleName:null,surname:"Aydin",slug:"sevcan-aydin",fullName:"Sevcan Aydin",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003QRfRpQAL/Profile_Picture_2022-03-24T08:49:06.jpg",biography:"Sevcan Aydın is an Associate Professor of Biotechnology Division in Department of Biology at Istanbul University in Türkiye. She obtained her bachelor's degree from Biology Department of Ege University. She obtained her Ph.D. in Biotechnology Programme of Istanbul Technical University. Her main research areas include genetics, environmental biotechnology and bioengineering.",institutionString:"Istanbul University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Istanbul University",institutionURL:null,country:{name:"Turkey"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429343",firstName:"Martina",lastName:"Ivancic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/429343/images/19998_n.jpg",email:"martina@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. 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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:"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:"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:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3828",title:"Application of Nanotechnology in Drug Delivery",subtitle:null,isOpenForSubmission:!1,hash:"51a27e7adbfafcfedb6e9683f209cba4",slug:"application-of-nanotechnology-in-drug-delivery",bookSignature:"Ali Demir Sezer",coverURL:"https://cdn.intechopen.com/books/images_new/3828.jpg",editedByType:"Edited by",editors:[{id:"62389",title:"PhD.",name:"Ali Demir",surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"872",title:"Organic Pollutants Ten Years After the Stockholm Convention",subtitle:"Environmental and Analytical Update",isOpenForSubmission:!1,hash:"f01dc7077e1d23f3d8f5454985cafa0a",slug:"organic-pollutants-ten-years-after-the-stockholm-convention-environmental-and-analytical-update",bookSignature:"Tomasz Puzyn and Aleksandra Mostrag-Szlichtyng",coverURL:"https://cdn.intechopen.com/books/images_new/872.jpg",editedByType:"Edited by",editors:[{id:"84887",title:"Dr.",name:"Tomasz",surname:"Puzyn",slug:"tomasz-puzyn",fullName:"Tomasz Puzyn"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"43828",title:"Role of Dendritic Cell Subsets on HIV-Specific Immunity",doi:"10.5772/52744",slug:"role-of-dendritic-cell-subsets-on-hiv-specific-immunity",body:'DC are key regulators of immunity in view of the fact that they are involved in immune responses against infectious diseases, allergy and cancer [1, 2]. Ralph Steinman was awarded the Nobel Prize for Medicine 2011 for DC discovery in 1973 [3]. Steinman and Cohn [3] described a novel cell type in mouse spleen, which they named ´dendritic cell´ due to their tree-like shape. The major function of DC is the induction of adaptive immunity in the LN.Yet, DC can also interact with innate immune cells, for instance natural killer (NK) and NKT cells [1, 4].
Upon entry of HIV into the host, the virus has to be transported from mucosal surfaces to lymphatic tissues, where it is transmitted to its primary targets, CD4+ T lymphocytes. This process is thought to be contrived by DC.
DC thereby play critical roles during HIV and SIV (simian immunodeficiency virus) infection.
The skin and mucosa are composed of two compartments, the epidermis and the dermis (skin) or stratified squamous epithelium and lamina propria (mucosa), each containing a major subset of DC - Langerhans cells (LC) reside in the suprabasal layers of the epidermis and epithelia [5], while dermal/interstitial DC are distributed throughout the connective tissue of the dermis [6, 7].
Both subsets represent immature DC that are very efficient in Ag uptake and processing. As immature DC (iDC), they reside in peripheral tissue, which they survey for invading pathogens. Upon encounter with antigen (Ag), DC mature (mDC) and migrate to the draining lymph nodes (LN). They pass through different maturation stages, which enable them to fulfill specific tasks such as the uptake, the processing and the presentation of Ag on major histocompatiblity complex (MHC) molecules to naïve T cells. In the T cell area of lymphatic tissue the mature DC stimulate Ag-specific CD4+ and CD8+ T cells to proliferate and develop effector function, such as cytokine production and cytotoxic activity. Effector T cells are recruited to inflamed peripheral tissue and participate in the elimination of pathogens and infected cells. This very particular life cycle illustrates why DC are called the ´sentinels of the immune system´ [8].
In humans, different DC subsets have been identified in blood, spleen and skin, but little is known respecting resident and migratory DC in human LN. This book chapter will review the major DC subsets found in humans and their role in HIV-pathogenesis. If data are available, also the role of the viral opsonization pattern and its impact on DC interaction will be discussed.
DC are divided into two main groups: conventional myeloid DC (cDC) and non-conventional plasmacytoid DC (pDC) (Figure 1). As recently described byDoulatov et al. (2010) [9], human multi-lymphoid progenitors can bring forth all lymphoid cell types, including monocytes, macrophages and DC. Nonetheless, most DC in steady-state emerge from a common myeloid progenitor [10]. DC areheterogenous subtypes with distinct functions, properties and localization [11]. DC progenitors migrate from the bone-marrow through the blood to lymphoid organs and peripheral tissues. There, they give rise to different cDC subsets (Figure 1). LC display an exception within the cDC group since they maintain in the epidermis independent on circulating precursors [12]. Within cDC, migratory and lymphoid-resident DC are distinguished: migratory DC travel from peripheral tissues to lymphoid organs, whereas lymphoid-resident DC populate lymphoid organs during their whole life-span and lack the migratory function. In humans cDC comprise Langerhans Cells (LC), dermal DC (CD103+ and CD103-), BDCA1+ (CD1c)- and BDCA3+ (CD141) DC, and the recently described CD56+ DC (Figure 1). They are localized in the skin, secondary lymphoid organs (spleen, tonsils) and blood. pDC develop in the bone-marrow and then they reside in lymphoid organs [13]. HLA-DR+CD123+pDC express BDCA2 and this cell subset is found in blood, secondary lymphoid organs as well as peripheral tissues, e.g. skin or lungs (Figure 1). The cDC subtypes and pDC express a different receptor repertoir and comprise distinct functions with respect to HIV spread, antiviral activity and transmission, which is reviewed below and shown in Figure 1 (Table adapted from Altfeld et al., [14]). Both cell types are resident in lymphoid tissues in the steady state, but during an inflammatory response, pDC and cDC are actively recruited to these tissues [15-17].
DC-subsets and functions during HIV-infection (Table adapted from
LC survey the basal and suprabasal layers of the stratified squamous epithelium of the skin and oral and ano-genital mucosa for invading pathogens [18-21]. Due to their ideal localization in mucosal tissues and their long dendrites to efficiently capture Ag, they comprise the first line defense against mucosal infections. After Ag acquisition, LC start to mature, as represented by up-regulation of co-stimulatory molecules (CD80, CD86, CD40), MHC class I and II molecules, CD83 and CCR7 and down-regulation of Langerin and E-cadherin [22].
Due to CCR7 up-regulation, the mature LC migrate to the LN along a CCL19 and CCL21-leu (leucine isoform of CCL21) gradient to efficiently prime T cells there [23]. Beside initiating an effective adaptive immune response, LC were illustrated by DeWitte et al. [24, 25] to also have important functions with respect to innate immune responses. Beside a specific set of TLRs (TLR2, 3, 5) and high expression of CD1a, LC express Langerin and contain Birbeck granules that might be crucial to their innate function [21, 26-29] (Figure 1). The C-type lectin Langerin interacts with non-opsonized HIV-1 (Figure 2) and other pathogens such as fungi and bacteria, via fucose or mannose residues. Thereby degradation of HIV-1 in Birbeck granules is promoted and HIV-1 dissemination is limited [24].
Co-localization of HIV and Langerin on CD1a+ Langerhans Cells isolated from human skin
Early investigations of HIV-LC interactions illustrated that LC are productively infected by HIV and that they efficiently transmit the virus to T cells [30-32]. These results suggested that HIV take advantage of the antigen-capturing properties of LC to reach the T cell zone in the lymphatic tissues and via this route, HIV can establish a productive infection of the host. However,
Engagement of Langerin trimers on the surface of LC induces formation of Birbeck granules, which are part of the endosomal recycling system and uniquely found in LC (Figure 3, lower right panel) [34]. Upon capture of mycobacterial lipoproteins by Langerin, these were exposed to CD1a molecules in Birbeck granules [35], which suggests that Birbeck granule formation displays a non-classical antigen processing pathway [20]. Also HIV-1 attaches to Langerin on LC and is subsequently routed to Birbeck granules, which points to a role of the granules with respect to degradation of viruses.
Studies by Gejitenbeek´s laboratory [24] showed that under homeostatic conditions, Langerin expressed on LC and acts as restriction factor for HIV infection. They demonstrated that, if HIV-gp120 attaches to Langerin, the viral particle is internalized and subsequently degraded in Birbeck granules. Thus, LC are protected from infection with incoming, non-opsonized HIV particles and HIV-1 is not disseminated throughout the host [24]. The rapid internalization of HIV-1 into LC by Langerin impedes interactions and subsequent fusion with CD4 and CCR5 and also prevents transmission to the main target cells of the virus, CD4+ T cells. Thereby, Langerin acts as a protective anti-HIV barrier during the first steps of HIV-1 infection, if the virus is non-opsonized and if sexually transmitted pathogens are lacking.
As demonstrated, if the host system is facing other sexually transmitted infections, the anti-HIV-1-barrier of LC is abrogated and HIV-1 transfer to susceptible CD4+ T cells is promoted [20, 36, 37]. Pathogens, such as Candida or Neisseria, directly interact with Langerin and compete with HIV-1-binding. Additional factors explaining the by-passing of the anti-HIV-1-barrier function of Langerin are that:
by high viral loads the receptor becomes saturated,
infections, e.g. Herpes simplex virus infection, down-regulate Langerin surface expression [20],
the HIV-1 entry receptors CD4 and CCR5 are up-regulated during additional sexually transmitted infections [37],
or the antiviral function of Langerin is reverted by inflammation-induced TNF-α (tumor-necrosis-factor α) production due to Candida albicans or Neisseria gonorrhoea [36].
These observations allow to conclude that during acute co-infection the anti-viral function of LC is significantly decreased.
Not only acute co-infection, but also opsonization of HIV with either complement fragments or specific Abs might result in reduction or abolishment of the anti-viral function mediated by Langerin (
In summary, during acute co-infection or by opsonization with complement fragments or Abs, the anti-viral function of LC is significantly reduced due to competition for Langerin or different receptor utilization. This facilitates HIV-1 infection of LC via CD4 and CCR5, intracellular uptake of the virus (Figure 3) and promotion of HIV-1 transfer to its targets, CD4+ T cells.
On the other hand LC were implicated in establishment of infection due to their location in the foreskin and due to compelling evidence that male circumcision efficiently reduces the risk to become infected with HIV-1 [43]. It was furthermore shown
Along with LC, HIV-1 firstly attaches to dermal (interstitial) DC upon entry at mucosal surfaces (Figure 1). Dermal DC are underlying the epithelium, do not contain Birbeck granules and express heterogenous amounts of CD1a [48].
Interstitial DC are localized in the dermis and oral, vaginal and colonic lamina propria [6, 49-52]. They are characterized by the expression of CD11c, high expression of various C-type lectin receptors (Langerin on CD103+ DC, DC-SIGN on CD103- DC, DEC-205 on both subsets), TLR2, 3, 4 and 5 and they secrete various cytokines upon pathogenic stimulation (Figure 1). Since there are only 2 studies available on human CD103+ DC and SIV [53, 54], the following chapter refers to CD103-, DC-SIGN+ dermal DC.
As shown in Figure 3, dermal DC (left panel) and LC (right panel), which emigrated from whole skin explants, take up variable amounts of HIV-1 particles. As demonstrated by Frank et al. [55], human and macaque DC interacted similarly with SIV and ample amounts of virus were captured by DC. Transmission electron microscopic analyses revealed that iDC, which are endocytically highly active, captured few viral particles near the periphery of the membrane, while mDC, which down-regulate the endocytic capacity, retained high amounts of virions in large vesicular compartments deeper within DC [55]. This points to a diverse entry and handling of virions within iDC and mDC.
Uptake of HIV into dendritic cells from human skin. Dendritic cells emigrated from whole skin explants were incubated with HIV for 2h and then fixed and embedded for transmission electron microscopy. Variable amounts of viral particles are taken up by dermal dendritic cells (left panels) and epidermal Langerhans cells (right panels). Lower panels show higher magnifications of membrane-enclosed virus particles in a dermal dendritic cell (left panel; some viruses marked with red/black). In a Langerhans cell (lower right panel) viruses can be seen docking onto the surface membrane (right asterisk) and already taken up into vesicular structures (left asterisk). A Birbeck granule is depicted in the inset as the identifying structure for Langerhans cells. N, nucleus.(Photos courtesy of Hella Stössel and Nikolaus Romani).
Beside the different handling of HIV-1 or SIV within iDC and mDC, opsonization of the virus with either complement fragments and/or Abs significantly affects the binding mechanism, internalization and infection of DC as well as their T cell stimulatory capacity [41, 42, 58]. As shown by Pruenster et al. [42], the complement cloud around the virus significantly blocked the accessibility of gp120 and therefore interfered with C-type lectin interaction.
Similar amounts of HIV-1 bound to the surface of DC independent on the opsonization pattern of the virus (Pruenster et al., 2005). The attachment of the differentially opsonized HIV-1-preparations was found to be specific (Figure 4 [
blocking α-DC-SIGN mAb inhibited interaction with non-opsonized HIV-1 (Figure 4, HIV),
blocking α-CR3mAb (TMG6.5) significantly interferred with binding of complement-opsonized HIV (HIV-C) to DC (Fig.4, HIV-C) and
blocking α-CD32mAb (AT10) inhibited binding of Ab-opsonized HIV-1 (Figure 4, HIV-Ig).
Additionally, we found variations respecting infection of DC with differentially opsonized HIV-1 preparations [41]. Productive infection of DC and LC with HIV-1 was described to be relatively inefficient compared to HIV-infection of CD4+ T cells and HIV- or SIV-infected DC are rarely detected
In contrast, HIV-1 coated with specific, non-neutralizing Abs significantly impaired infection of and integration in DC and also ´
Despite the low-level productive infection of DC, non-opsonized HIV-1 is very efficiently transmitted to T cells either via de novo (´
Binding of differentially opsonized HIV (non-opsonized HIV, HIV-C, HIV-Ig) in absence and presence of a blocking anti-human DC-SIGN, CR3 [CD11b] (TMG6.5) or CD32 (AT-10) antibodies. Binding of non-opsonized HIV was signficantly decreased in the presence of a blocking anti-DC-SIGN Ab, but not affected by pre-incubation of the cells with a blocking anti-CR3- or CD32-Ab (white bars). HIV-C-interaction with DC was inhibited using a blocking anti-CD11b (CR3)-Ab TMG6.5, but not by anti-DC-SIGN or CD32 (grey bars). Binding of IgG-opsonized HIV was inhibited by using a blocking anti-human CD32, but not DC-SIGN or CD11b-Ab (black bars).
Lastly, the antigen-presenting capacity of DC was also shown to be modulated by the opsonization pattern of the virus [58]. Earlier studies illustrated the role of complement opsonization respecting induction of effective CTL responses against viral infections, but the exact mechanism was not determined [64-66]. The exclusive role of DC in priming naïve CD8+ T cells in response to exogenous cell-associated as well as endogenously synthesized Ags has been shown [67, 68]. Endogenously synthesized antigens from DC infected with LCMV (choriomeningitis virus) mediated strong CTL responses, while macrophages and B cells infected with LCMV did not induce CTLs [68].
We recently found that opsonization of retroviral particles with complement fragments enhanced the ability of DC to induce CTL responses both
Additionally, we demonstrated that in contrast to complement opsonization, antibody-coating of the viral surface attenuated the CTL-stimulatory capacity of HIV-exposed DC [69]. In some HIV-1-positive individuals, high levels of antibodies and low levels of complement fragments coat the HIV-1 surface and therefore we investigated the effects of the non-neutralizing Abs bound to the surface of HIV-1 on the CTL-stimulatory capacity of DC. We observed
Preferential expression of CCR5 on immature LC and DC restricts the transmission of X4-tropic isolates at the site of infection. Additionally,
BDCA1+ myeloid DC can be directly isolated from human blood. This population was described to be reduced in the blood of HIV-infected individuals [76-78]. We found that BDCA1+ DC exerted a decreased transmission of HIV-1 to autologous CD4+ T cells, when the virus was opsonized with specific IgGs in contrast to non- or complement-opsonized HIV-1 and when the T cells were added delayed [41]. When CD4+ T cells were immediately added after washing the differentially loaded DC, the same infection efficiency was observed using HIV, HIV-C or HIV-Ig [41]. The two-phase transfer of HIV to DC as described above (
BDCA3+ DC represent the human equivalent to mouse CD8α+ DC and they are the major producers of IFN-λ in response to dsRNA poly I:C [80].As recently described by Dutertre et al. [81] using an 11-color flow cytometric strategy, circulating BDCA1+ DC and BDCA3+ DC counts were reduced in 15 viremic, untreated patients compared to 8 HIV-1-positive individuals under treatment and 13 healthy donors. By using this method, they illustrated that both blood DC subsets expressed characteristic lineage markers: BDCA1+ DC expressed CD14, while particularly BDCA3+ DC displayed CD56 on their surface. BDCA3+ DC were shown to be more significantly down-modulated in viremic patients compared to controls [82] and it remains to be investigated by longitudinal studies, if combined antiretroviral therapy can restore the pool of circulating myeloid BDCA1+ and BDCA3+ DC.
Blood CD56+ DC were recently described by Gruenbacher et al. [83] and comprise intermediate-sized lymphocytes with an HLA-DRhigh, CD80+ and CD86+ expression profile. Upon cultivation they acquire DC-like morphology with increased levels of above mentioned surface markers. Upon stimulation, they are able to efficiently stimulate CD56+γδ T cells, which results in secretion of IFNγ, TNF-α, and IL-1β [84]. The role of CD56+ DC respecting HIV-1 infection and pathogenesis needs to be further investigated.
Plasmacytoid DC (pDC) (Figure 1) or type 1 IFN-producing dendritic cells are innate immune cells in blood, which are specialized in releasing massive amounts of IFNα and IFNβ upon viral challenge, including HIV-1 [83]. They constitute <0.2-0.5% of peripheral blood mononuclear cells (PBMC) [85] and in humans, pDC express the characteristic surface markers BDCA-2 (CD303, CLEC4C) and CD123 along with BDCA4 (CD304, NRP1), but they do not express CD11c, a marker of myeloid DC, or CD14 [86].
pDCs are key players of the innate immune response
Data by Zhou et al. [99] indicate that subsequent to HIV-1 challenge, signaling via TLR7 triggers autophagy and increased IFNα production from human pDC. The IFNα secretion mediated by an autophagy-dependent pathway may play an important role for T cell triggering during HIV-1 pathogenesis.
Beside acting as pro-inflammatory cells, pDC also provide negative regulatory signals and thus induce tolerance. pDC express IDO (indoleamine 2,3-dioxygenase) and PDL-1 (programmed death ligand; 1) which are associated with the negative modulation of T cell responses and regulatory T cell induction [100-102].
During acute HIV-1 infection, NK cells are recruited and activated by pDC to the sites of infection and to LN due to IFNα secretion [103, 104]. IFNα was demonstrated to increase the perforin levels in NK and CD8+ T cells. At the sites of infection ´DC-editing´ occurs by NK cells, since activated NK cells delete immature pDC to select for the more immunogenic mature pDC [105-108].Beside NK cell recruitment and activation, pDC-secreted IFNα promotes maturation and migration of other DC subsets. Due to their localization, it is unlikely that pDC are involved in HIV-1 capture, transport and transmission, but they are supposed to control HIV-1 in the acute phase of infection due to their immediate antiviral and NK priming activity.
Chronic exposure to HIV-1 leads to hyperactivation of pDC resulting in simultaneous type I IFN secretion and IDO expression. Thus, pDC concurrently exert cytotoxic and suppressive effects on T cells during chronic HIV-1 infection [109].
HIV-1 infection not only disrupts DC homeostasis within myeloid DC subsets, but also pDC homeostasis is defective during chronic HIV-1 infection. cDC and pDC are lost from blood, which correlates with high viral loads and low CD4+ T cell counts [76, 110-113]. Deficiencies in pDC function were among the earliest observations of immune dysfunction in HIV-1 infection and some of the earliest studies of the ´natural IFN-α-producing cells´ (i.e. pDC) illustrated that PBMC from AIDS patients were severely compromised in their ability to produce IFN-α
Cell death and/or a failure of bone marrow progenitors to differentiate into pDC might contribute to the loss of pDC from blood of chronically infected individuals. In non-pathogenic models of SIV infection, no depletion of blood pDC was observed [114, 115] and HIV-1-positive individuals, who are able to control infection (= long-term non-progressors) were also shown to have increased numbers of blood pDC [111].In contrast, it was described that during HIV-2 infection, which is highly attenuated compared to HIV-1 infection in humans, also the numbers of blood pDC is found reduced [116]. Thereby, the exact role of pDC depletion during HIV infection is not clear yet.
The depletion of cDC from the sites of infection was ascribed to a higher expression of CCR7 on the surface of cDC and a signficantly increased CCL19 expression in LN of SIV-infected animals, thus suggesting that inflamed LN lure cDC away from the sites of infection early during progressive SIV infection [117]. A similar mechanism can be imagined for pDC, which are recruited to inflamed LN via CXCL9 and E-selectin [16, 118], but the pDC loss could also be due to direct infection, enhanced apoptosis or CD95 up-regulation [119-123].
Not only pDC numbers are decreased during on-going HIV-1 infection, but also the quality of the cells is suffering. They exert a reduced ability to migrate towards the CXCR4 ligand CXCL12 [124], they stimulate Treg cells to dampen HIV-1 immunity and they furthermore shift the Treg-Th17 balance [125, 126]. So far, interactions of differentially opsonized HIV-1 preparations with pDC has not been investigated.
As follows of investigations on HIV-1 in the last 30 years, antibody responses against the virus are not effective and cellular immune responses not powerful enough to suppress or even control HIV-1. DC, the prime inducers and regulators of immunity and tolerance, are crucial in designing modern vaccines [127-130]. Therefore, nowadays vaccine science shall combine established classical vaccine approaches with new attempts based on the expanded immunological knowledge.
Innate and adaptive immune responses are needed to generate efficient, long-lasting protection. Immediate innate responses involve activation of the complement system, ligation of pattern recognition receptors e.g. TLRs, C-type lectins, activation of NK cells, cDC and pDC, and type I, II, as well as III interferons. For viral clearance, the optimal balance between CD4+ and CD8+ T cells is required during the adaptive immune responses. Current HIV-1 vaccination strategies include the use of peptides or monocyte-derived DC exposed to chemically inactivated HIV-1 and aim in designing a vaccine efficiently inducing both, cellular and humoral immune responses [131-133]. So far, disappointing results have been achieved in clinical trials targeting either cellular [134, 135] or humoral immunity [136, 137]. The most prominent AIDS vaccine trial so far was the RV144 in Thailand [138], which evoked strong, but transient Env-specific CD4+ T cell and Ab responses, but only weak HIV-specific CD8+ T cell responses [131, 138].
HIV-1 induces immediate responses of the immune system upon entering mucosal surfaces. There, the complement system constitutes a first line of defense against the virus. Recently, we illustrated an important role for complement opsonization of retroviruses as an endogenous adjuvant for DC-mediated CTL-induction [58].
Efficient early CD8+ T cell responses are crucial in controlling HIV-1 replication and their key role in HIV-1 control is additionally substantiated by association of certain HLA class I alleles and an improved disease progression [139-141]. In view of our very recent observations ([58], [69]), we propose that CD8+ T cells are efficiently primed by DC during acute viral infection, particularly by enhanced infection of DC with HIV-C [41]. Thus, more efficient presentation of endogenously synthesized viral Ags via HLA-ABC [41], and ore efficient cross-presentation from incoming complement-opsonized HIV-1 are mediated. In contrast, Ab-opsonization of HIV-1 weakens the CTL-induction by modulation of DC function and might influence future vaccination strategies [69].
As shown by Lu et al. [142-144]
LC were described to allow more cross-priming of CD8+ T cells, while dermal DC are more specialized in primingnaive CD4+ T cells [145]. The finding that complement-opsonization of HIV prior loading of DC significantly enhanced the CD8+ T cell-stimulatory capacity of the cells in combination with using specific DC subtypes might efficiently improve future vaccination strategies and there is good reason to address DC of the skin, especially Langerhans cells, for purposes of vaccination.
A greater understanding of the innate and adaptive processes and the different functions of DC subsets to HIV-1 infection will lead to development of an effective vaccine.
The authors would like to thank Nikolaus Romani and Hella Stössl for providing the transmission electron microscopic picture.
The work of the authors is supported by the Austrian Science Fund [FWF, P22165 and P24598 to DW], the Tyrolean Science Fund [TWF, project: D-155140-016-011 to WP] and the OeNB [project: 14875 to WP].
The conventional microwave-tubes, such as traveling-wave tubes (TWSs) and klystrons follow the Pf2 law. As per this law, the product of maximum power (
The gyrotron is the most suitable source for the heating of plasma in Tokamak for controlled thermoneuclear fusion reactors. Gyrotron is being used as the heating source for electron cyclotron resonance heating (ECRH) as well as for the electron cyclotron current drive (ECCD).
Gyro-devices comprise of a family of microwave devices and gyrotron is one among those. However, gyrotron being the most popular gyro-device, the entire gyro-device family is sometime referred as gyrotrons. Various other commercially available gyro-devices are: gyro-klystron, gyro-traveling wave tubes (gyro-TWT) and gyro-twistron (a combination of Gyro-TWT and Gyro-Klystron).
In a gyro-device, a hollow electron-beam is generated with the help of a special kind of electron gun, known as magnetron injection gun (MIG) operating in temperature-limited regime of thermionic emission. This hollow electron beam is made to gyrate at cyclotron frequency with the help of a strong axial magnetic field. Subsequently, this gyrating electron beam is passed through an interaction structure, where the electron-beam interacts with the electromagnetic-wave (EM-wave). In case of gyrotron, the interaction-structure is an open-ended cavity. In case of gyro-TWT, the interaction structure is waveguide with an input and output coupler. When the cyclotron frequency synchronizes with the frequency of the EM-wave (frequency of EM-wave supported by the cavity in case of gyrotron and frequency of the EM-wave fed at the input coupler in case of gyro-TWT) the beam-wave interaction takes place. The transverse kinetic energy of the electron-beam gets converted to electromagnetic energy. Hence, the EM-wave gets generated (in gyrotron) or amplified (in gyro-TWT).
Let us now briefly discuss the origin of gyrotrons. It has been well known since the mid-fifties that there appeared to be a limit to the upper frequency at which most vacuum microwave devices could be made to operate with sufficient power and efficiency, primarily due to the reduction of physical size of the components of the device with increase of frequency [13]. This problem can be explained as follows: As the frequency of operation of the device increases, the dimension of the waveguide or cavity or the loading elements inside the waveguide (such as helix in case of helix-TWT) become uncomfortably small, as their physical size is closely related to the operating wavelength of the device. Furthermore, since the depth of penetration of the field generated by the electromagnetic wave is proportional to the operating wavelength, the field penetration inside the loading-element reduces with the increase of operating frequency. Hence, in order to have a proper interaction between the electron-beam and electromagnetic wave, electron-beam needs to be placed closer to the structure carrying electromagnetic wave, if we wish to retain an acceptable efficiency of beam-wave interaction [1, 2]. All these awkward requirements clearly indicate an urgent need for a radical change of approach. In conventional vacuum electronic slow-wave devices (such as TWT), periodic loading elements are required for slowing down the phase velocity of the electromagnetic wave (slow wave interaction: vph < c) so that the phase velocity becomes synchronized with the velocity of the slow space-charge wave produced by a perturbed electron beam. In case of helix-TWT, helix acts as periodic loading element, alternatively known as slow-wave structure (SWS). Whereas in gyro-device, alternatively known as fast-wave devices, the periodicity in the propagating medium is removed and the periodicity is brought in-to the electron-beam. The interaction now takes place with an electromagnetic wave whose phase velocity is higher than the free-space velocity of light (fast wave interaction, vph > c) [1, 2, 3]. Instead of periodicity of the loading element, the periodicity of the electron-beam comes into play. This leads to a quasi-synchronism between the electromagnetic wave and the electron-beam.
Gyro-devices comes under the category of Bremsstrahlung radiation device [13]. Here, instead of periodic show-wave-structure, the electron beam is made periodic by generating a hollow electron-beam gyrating under the influence of a strong axial magnetic field. When this electron beam is perturbed, two cyclotron waves get generated, namely slow and fast cyclotron wave. When the velocity of the fast cyclotron wave is synchronized with EM-wave, beam-wave interaction takes place. That’s why these devices are known as fast-wave device.
A variety of interaction stricture geometries are proposed in the literature [9, 11, 12, 13] for gyro-devices. In case of gyrotron, the interaction structure is an open ended cavity. Well directed and concentrated efforts were made in the mid-seventies by Granastein and his team at the Naval Research Laboratory (NRL) [13], as well as Gapanov and his team at IAP, Russia [14] who, with some help from others, succeeded in mounting an extensive research effort in the whole area of Bremsstrahlung radiation device, which include free-electron lasers as well as gyrotrons. Since then, gyro-devices have developed very rapidly to offer prodigious amounts of power, and very high efficiency of the order of 50% or more. Figure 1 shows capabilities of various vacuum electronic devices in terms of frequency and average power. It’s evident from the figure, for frequencies above the Terahertz range, laser devices are most suitable source for generation of electromagnetic wave. Again, for frequencies below the millimeter-wave range, conventional microwave tubes are most suitable source for the generation of high power. Gyrotron fits in between these two frequency regimes. Gyrotrons are best suited when the operating wavelength is approximately 1 mm and output power requirement is between hundreds of kilowatts to few megawatts. That’s why Gyrotron is found to be the most suitable source for the heating of plasma.
Domain of microwave tubes/ laser devices.
Ever since the advent of cyclotron-resonance maser (CRM) instability devices, a vast amount of research work has been carried out and a number of gyro-devices have been developed. Out of these, the most popular device is gyrotron (alternatively known as gyro-monotron). The other two commercially available gyro-devices widely used in radar applications are, gyro-TWT [3, 8], and gyro-klystron [3]. However, the entire class of gyro-devices are usually referred as gyrotron. There are few less popular gyro-devices, namely, Gyro backward-wave oscillator (gyro-BWO), gyro-twystron [3] (a combination of gyro-TWT and gyro-klystron), cyclotron autoresonance maser (CARM) and slow-wave cyclotron amplifier (SWCA) [13]. Technology for these devices are not as matured as for gyrotron, gyro-TWT and gyro-klystron. Some of the gyro-devices are oscillators and some are amplifiers. Same is brought out in the Table 1.
Oscillator | Amplifier |
Gyrotron(Gyro-Monotron) | Gyro TWT |
Gyro Backward Wave Oscillator | Gyro Klystron |
Gyroton | Gyro Twistron |
CARM | Cyclotron Autoresonance Maser (CARM) |
Slow Wave Cyclotron Amplifier (SWCA) | |
Gyroton-TWT | |
Magnicon |
The complete family of gyro-device.
In Table 1, the most popular gyro-device names are written in red. As is evident from the Table 1, cyclotron autoresonance maaser (CARM) can be configured both as amplifier as well as oscillator.
In the following section, two most popular gyro-devices, namely, gyrotron, and gyro-TWT are discussed in brief with the schematic diagrams.
A schematic diagram of the gyrotron with axial output of cavity mode is shows in Figure 2(a). The schematic view of high-power gyrotron with radial output of Gaussian beam is shown in Figure 2(b). Here the beam-wave interaction take place in an open-ended cavity. The hollow electron-beam from the electron-gun (known as magnetron injection gun) is injected into a region with very strong axial magnetic field [3, 6, 7, 8, 9, 10]. Magnetic flux densities of the order of several Tesla are normally required and this usually necessitates the use of superconducting magnets [6].
(a): Gyrotron with axial output. (b): High power Gyrotron with radial output of Gaussian beam.
The beam-wave interaction takes place in the interaction cavity region. In order to avoid the thermal issues, gyrotrons usually incorporate a highly overmoded cavity. The reported continuous wave (CW) and pulsed power capabilities of the gyrotron are three order of magnitude higher than the conventional microwave oscillators.
In case of axial output gyrotrons (Figure 2(a)), output millimeter-wave generated in the cavity propagates along the axis of the gyrotron and comes out of the gyrotron through an output-window. The spent-electron beam (the electron-beam after the beam-wave interaction) gets collected in the collector. In case of gyrotron with radial-output (Figure 2(b)), the cavity-resonator mode of EM-wave gets converted to Gaussian (TEM00) mode with the help of a quasi-optical launcher (QOL) and 3 or 4 mirrors. The Gaussian beam comes out of the gyrotron radially (perpendicular to the axis of gyrotron) through the output-window and the spent electron-beam gets collected in the collector.
Gyro-TWT is a high power millimeter-wave amplifier [3, 8]. This is used in millimeter-wave radars. Gyro-TWT is also used for electron-cyclotron current drive (ECCD) for Tokamak. In this device, the interaction-cavity is replaced by a non-resonant structure (waveguide) to produce beam-wave interaction. This device has the potential of amplifying EM-powers of 2 order of magnitude higher than the conventional TWT. Gyro-TWT provides a high spectral quality amplification over a narrow bandwidth. The device interaction essentially involves a narrow band resonance between the electron-beam and the electromagnetic-wave near the waveguide cut-off due to the dispersive nature of the waveguide interaction structure. However, wideband coalescence is possible by proper dispersion shaping of the waveguide. Axial phase synchronism is required between the traveling wave and the gyrating electron. Techniques are being used to increase the band-width by tapering the magnetic field or by periodically loading the waveguide structure. The cross sectional view of gyro-TWT is shown in the Figure 3.
Gyro TWT.
In a gyrotron, the electron beam, which is normally in the shape of a thin hollow cylinder, is injected into a region with strong axial magnetic field and passed through a cylindrical cavity or waveguide region containing an electromagnetic wave with an azimutal component of electric field [1, 2, 3]. The rotational velocities of the electrons are normally 1.2 to 2 times the axial velocity. So, majority of the electron energy is rotational.
Because the magnetic field is very large, the orbit diameter for the electrons is very small. As a result, the thickness of the hollow electron beam is several times the diameter of the electron orbit as shown in Figure 4, and in effect, the hollow electron-beam contains a large number of small beams, referred as beamlets [2, 6]. Figure 4 shows the thickness of the hollow electron-beam as twice the diameter of beamlet.
Gyrotron cross section showing electron trajectories.
The basic operating mechanism of gyrotron can be explained by considering the interaction of a single beamlet of electrons with the electric field. In Figure 5 it is assumed that electrons in a single beamlet are initially uniformly distributed along a single helical path prior to interaction with the RF electric field. The electrons are assumed to rotate in the counter clockwise direction as they move through the RF field. The rotational frequency of electrons is the cyclotron frequency, which is given by
Bunching of electrons in a Gyrotron.
Where,
Where
Where,
The radius of the gyrating orbit, alternatively known as Larmor radius (
Where,
Now, referring again to Figure 5(a), when the electric field is such that it tends to accelerate electrons (top of the orbits), the electron mass is increased and so the cyclotron frequency (
If the cyclotron frequency (ωc) is somewhat lower than the frequency of the electromagnetic wave (ω), then the position of the bunches along the helical orbit is delayed with respect to the phase of the applied field as indicated in Figure 5(b). Hence, the bunched electrons face a decelerating field and give-up their kinetic energy to the field. As the electron bunches rotate in near synchronism with the alternating RF-field, they continue to give-up energy on each half-cycle of rotation.
The interaction that has just been described for the electrons in a single beamlet in a gyrotron also takes place in the other beamlets. Thus, the electron distribution becomes as indicated in Figure 6. As the direction of the electric field alternates, the direction of motion of electron also alternates, and so the electrons throughout the transit period of the electron-beam give-up energy on each half cycle of operation. This is how the beam-wave interaction happens.
Electron motion in relation to direction of electric field in a gyrotron.
With the proper shape of the RF-field, it is possible to excite harmonic mode of interactions with the electrons [1, 2, 8, 13, 14, 15]. As shown in Figure 7, the EM-wave field oscillates at a frequency twice the cyclotron frequency [2], i.e., ω = 2ωc. The direction of the field reverses in the center of the electron orbit. Thus, an electron that is initially decelerated by the field is moving transverse to the field when the field reverses, and so does not have its orbital energy changed. By the time the field reverses again, the electron has moved 900 around its orbit and is again in a decelerating field. Thus, during each full orbital motion of electron, the RF-field goes through two complete cycles. Hence, for harmonic mode of operation, for a given operating frequency, the cyclotron frequency is half the value used in fundamental mode of operation. As a result, the magnetic field is reduced by a factor of two. Operation at frequencies higher than the second harmonic are also being examined [15], but the intensity of the interaction is reduced, making the efficiency of gyrotron low.
Harmonic interaction of an electron and a field varying at twice the cyclotron frequency. (a) At an arbitrary time T, (b) At half RF cycle after T.
For harmonic mode operation, the frequency of operation of the gyrotron is approximately given by
where, s is an integer, representing the harmonic number. Value of s equals to 2 corresponds to second harmonic operation. It signifies that the electromagnetic-wave frequency of the gyrotron is chosen to be twice the cyclotron frequency. Harmonic operation reduces the magnetic field requirements by factor of s (
In a gyrotron, a hollow electron beam gyrating at cyclotron frequency under the influence of a strong axial magnetic field interacts with the transverse electric field excited inside the cavity. If the cyclotron frequency is synchronized with the frequency of millimeter wave supported by the cavity (cut-off frequency of the cavity) for the selected higher order mode, millimeter wave gets generated. This phenomenon is known as cyclotron resonance maser (CRM) interaction. The hollow gyrating electron-beam is generated with the help of magnetron injection gun (MIG). The gyrating electron-beam is passed through a beam-tunnel and fed into an open ended interaction-cavity. The millimeter wave generated in the cavity region diffracts out with the help of a non-linear taper (NLT). The waveguide mode of electromagnetic-wave is covered to Gaussian mode with the help of a quasi-optical launcher (QOL) and mirror units. The millimeter wave is taken out of the gyrotron with the help of a high power millimeter-wave window. The spent electron-beam is collected in a collector. The required axial magnetic field throughout the gyrotron, starting from the MIG to collector is provided by a magnetic-system consisting of a main superconducting-magnet along with a number of non-superconducting solenoid magnets. Out of all these subsystems, MIG and interaction-cavity are the most important subsystems of gyrotron. The following section describes some of these main subsystems of gyrotron.
Most high power gyrotrons use magnetron injection guns (MIGs), which produce annular electron-beams in which electrons gyrates in cyclotron frequency. The gyrating frequency is so chosen that the beam-wave interaction at desired mode can take place. For good interaction-efficiency, the transverse velocity component of electron should be as large as possible. A spread in transverse velocity results in a spread in axial velocity, and eventually reduces the efficiency of the gyrotron. Hence, the electron velocity spread should be kept as small as possible [8]. The cut-section view of a typical MIG with anode is shown in Figure 8 indicating various parts of MIG.
Cut-section view of a typical MIG.
The electrons are emitted from a annular cathode operating in temperature limiting regime of thermionic emission [2, 3]. MM-type dispenser cathode is used as emitter. The electron motion is taking place in crossed electric and magnetic fields so that the electrons follow helical trajectories around the magnetic flux lines with the electrons gyrating in cyclotron frequency. The accelerating potential of 20–70 kV is applied between the cathode and the anode. The MIG can have a diode or a triode configuration. In the triode configuration, there are two anodes, namely modulating anode and accelerating anode. In triode configuration, second anode provides the main accelerating potential. Whereas, the first anode (which is closer to cathode) is used to fine-tune the velocity pitch-factor of the beam (ratio of transverse to axial beam-velocity) as well as for pulsing the beam (i.e., for switching the beam ON and OFF). Gyro-TWT’s usually incorporate triode MIG. In diode configuration, there is only one anode. Diode MIG needs much simpler power-supply for providing the necessary voltages. However, on the flipside, gyrotrons with diode MIG have lesser control over the beam.
The gyrating electron beam enters the interaction cavity, where the beam-wave interaction takes place [3, 6, 8, 9, 10, 11, 12, 13]. This is an open ended overmoded cavity operating near cut-off [3, 6]. The interaction cavity generally consist of 3 sections, namely downtaper-section, straight section and uptaper-section. The shape of the cavity is dependent on the mode of the electromagnetic field with which the beam is intended to interact and also the harmonic number of interaction. The required diffractive quality factor of the cavity is achieved by proper fine tuning of the cavity shape. Schematic drawings of a typical Gyrotron cavity is presented in Figure 9. The down-tapering is offered to the input-end of the cavity. This prevents the millimeter wave from back-traveling towards the MIG. The up-tapering is offered in the output-end of the cavity. The up-tapering helps the millimeter-wave to diffract out of the cavity. In case of coaxial gyrotrons, a coaxial insert is placed at the center of the cavity. The main beam-wave interaction takes place at the straight section of the cavity.
A typical Gyrotron cavity.
The millimeter-wave signal generated in the cavity needs to diffract out of the cavity. The same is achieved by the non-linear taper (NLT). This NLT is basically a tapered waveguide section with a specific tapering profile. A raised-cosine profile is incorporated in the NLT region to avoid reflection of electromagnetic-wave. This section acts as an interface between the interaction cavity and the QOL [6, 16, 17, 18, 19, 20]. Generally interaction cavity operates at a mode much higher than the dominant mode of the cavity. This enable the use of much higher cavity dimension and volume and this in-turn eliminates the bearing on the maximum power handling capacity at higher frequencies of millimeter-wave and sub-millimeter-wave regime. Broadly, the cavity operating modes are divided into three categories, namely, TE0 n mode, TEm n (m > n) mode and TE1 n mode. TEm n mode, when m> > n, is called the whispering gallery mode. This mode is most widely used in gyrotrons for plasma heating applications. The relative merits and demerits of these modes are presented in the Table 2.
Gyrotron cavity modes.
The radius of the hollow electron beam generated by MIG is generally much larger than the required hollow beam radius at the cavity region. The purpose of the beam-tunnel is to gradually bring down the beam radius to the value needed in the cavity region. Beam-tunnel is basically a cylindrical waveguide structure placed between the anode and interaction-cavity. The inner radius of the beam-tunnel at the anode end is matched to the anode inner radius and at the cavity end is matched to the input inner radius of the cavity. In order to ensure that the beam-tunnel does not take part in interaction, lossy dielectric material is placed inside the beam-tunnel. One of the popular configuration of beam-tunnel is a stack of alternate metal (OFHC copper) and lossy ceramic (AlN, SiC) rings stacked inside the cylindrical waveguide of beam-tunnel (Figure 10). The axial length of the beam-tunnel is so chosen that that the electron beam undergoes an adiabatic compression as it propagates from the MIG to the cavity, i.e., the beam trajectories follows the magnetic flux lines. This configuration ensures maximum beam laminarity and minimum beam-turbulence. Cavity.
Cut section view of a beam tunnel.
The purpose of the quasi-optical launcher (QOL) is to convert the cavity mode of EM-wave into a Gaussian (TEM00) mode. This is accomplished with the help of a helically-cut waveguide section (QOL) followed by 3 or 4 toroidal mirrors system. QOL consist of a mildly tapered waveguide structure with helically cut end (known as Vlasov launcher) with dimple patterned inner surface (Denisov type surface deformation). Millimeter wave is launched from the QOL to the mirror system [16]. After passing through the mirror system, a Gaussian beam (with more than 98% Gaussian mode purity) is emerged. A typical QOL and 3 mirrors for converting cavity mode to Gaussian (TEM00) mode is shown in Figure 11. The Gyrotron with Gaussian output is most suited for plasma heating applications. Because, the Gaussian millimeter-wave beam can be transmitted through a waveguide over a very long distance with very little attenuation. Hence, the gyrotron can be placed away from the plasma vessel. Sometimes, the Gaussian beam is further converted to HE11 mode with the help of a matching optic unit (MOU) placed external to gyrotron and then transmitted to the plasma vessel. This arrangement further reduces the attenuation of the beam.
A typical QOL for converting TE6,2 cavity mode to Gaussian mode.
The millimeter-wave signal is finally taken out of the gyrotron with the help of the high-power output window. This window consists of a ceramic disc which isolates the ultra-high vacuum environment inside the gyrotron enclosure from the outside atmosphere. The ceramic disc material and thickness is so chosen that it appears almost transparent to the electromagnetic-wave and the millimeter-wave comes out of the gyrotron through the window with minimum attenuation. Also, a material, which is a good thermal conductor but bad electrical conductor, is chosen for window. Usually single disc window is used. However, for the purpose of VSWR matching, sometime double disc window may be incorporated. For short-pulse operation, sapphire, beryllium-oxide (BeO) or boron-nitride may be used as window ceramic materials. For long pulse high-power operation, chemical vapor deposition (CVD) diamond is generally used as the window material due to its very high thermal conductivity.
After the electron-beam comes out of the interaction-cavity, the spent electron-beam gets collected in the collector. The kinetic energy of the spent-electron beam (the electron-beam which has already undergone beam-wave interaction) gets dissipated in the collector. Hence, if the electronic-efficiency of a gyrotron is 40%, 60% of the electron beam power gets dissipated in the collector. Since the dissipated power in the collector is very high, the thermal management of collector is a very critical issue. The cut-section view of a typical collector is presented in the Figure 12. In some of the high power gyrotrons, a low frequency magnetic sweeping coil is used for sweeping the electron-beam along the length of collector to avoid creation of hot-spots. For the enhancement of overall efficiency of gyrotron, multistage depressed collector (MDC) is used, where the collector is kept at a negative potential with respect to cavity.
Cut-section view of a typical collector.
The purpose of the magnetic system is to generate required axial magnetic field profile needed for the cavity as well as the MIG and collector. For lower frequency operation, non-superconducting air-cooled solenoids are preferred. However, for higher frequency operation (i.e., for gyrotrons operating at W-band or beyond), superconducting magnets are being used. The state-of-the-art magnets employ cryogen free superconducting magnet technology. Which eliminates the need of re-filling of liquid helium. Some researchers have reported gyrotrons developed with Samarium-Cobalt (Sm2Co17) permanent magnets and special type of room temperature solenoid made out of copper foil. Such gyrotrons usually operate at higher harmonic mode of interaction.
Gyrotrons have wide range of applications. These applications coves the domain of scientific research, industrial heating, homeland security and defense. Same is shown in tree diagram (Figure 13).
Applications of gyrotron.
Majority of gyrotrons developed worldwide are being used for the electron cyclotron resonance heating (ECRH) of plasma in the controlled thermoneuclear fusion reactor [7]. The plasma is kept confined in the plasma vessel with the help of very high value of superconducting magnetic field (magnetic confinement). The magnetically confined plasma is then exposed to very high power millimeter wave beam generated with the help of a gyrotron. This elevates the temperature of the plasma to 1000000 C. At this temperature, fusion reaction takes place. Millimeter-wave beam generated by a gyrotron is also used for the electron cyclotron current drive (ECCD), electron cyclotron resonance ion source (ECRIS) and also for the diagnostics cooling tower system (CTS). For the ITER (international thermoneuclear experimental reactor) project, it’s proposed to use 20 numbers of 170 GHz long-pulse gyrotrons to generate combined heating power of 24 MW. For this purpose, till now, the highest order mode number attempted is TE34,19 for the generation of 2 MW of continuous power at 170 GHz. The photograph of a 2 MW gyrotron for ECRH application is shown in Figure 14. The photograph of a ECRH System (Stellarator W7-AS) with 140 GHz gyrotron is shown in Figure 15.
2 MW Gyrotron for ECRH application.
140 GHz Gyrotron based ECRH system (Stellarator W7-AS).
Other important scientific research application of gyrotron is in the area of spectroscopy. This includes, electron spin resonance (ESR) spectroscopy, dynamic nuclear polarization – nuclear magnetic resonance (DNP-NMR) Spectroscopy, X-ray diffraction magnetic resonance (XRDMR) spectroscopy etc. Also, W- band frequency of 95 GHz being an atmospheric window, gyrotrons operating at W-band are having special significance in connection with defense and homeland-security [17, 18]. The active denial systems (ADS) for controlling low-intensity conflicts, uses 95 GHz gyrotron. Also a number of millimeter-wave radar systems, such as space surveillance radar, space derby radar, imaging radar and weather radar uses W-band gyrotron as well as gyro-TWT/ gyro-klystrons.
Worldwide, a number of research institutions, academic institutions and industries are working in the field of gyrotron, with frequency varying from lower end of microwave range (8 GHz) to 1 THz. The output power of these gyrotrons also ranges from 100 s of kW to few MW. Pulse duration also varies from few milliseconds to full continuous wave (CW) operation. The efficiency of gyrotron varies from 10–70%. The worldwide scenario of Gyrotron for plasma heating purpose are presented in the Tables 3 and 4 [7, 11, 12, 13, 19, 20, 21].
Institute | Frequency (GHz) | Mode | Power (MW) | Efficiency (%) | Pulse length (Sec) | |
---|---|---|---|---|---|---|
Cavity | Output | |||||
CPI, USA | 28,35 | TE02 | TE02 | 0.2 | 37 | CW |
CPI, USA | 53.2,56,60,70 | TE01/02 | TE02 | 0.23 | 37 | CW |
CPI, USA | 70.15 | TE10,3 | TEM00 | 0.6 | 47 (SDC) | 2.25 |
CPI, USA | 84 | TE15,4 | TEM00 | 0.56 | 44 (SDC) | 2.0 |
CPI, USA | 94.9 | TE6,2 | TEM00 | 0.12 | 50 (SDC) | CW |
Gycom, Russia | 68 (70) | TE9,3 | TEM00 | 0.5 (0.68) | 50 (48) (SDC) | 1.0 (3.0) |
Gycom, Russia | 75 | TE11,5 | TEM00 | 0.8 | 70 (SDC) | 0.1 |
Gycom, Russia | 82.7 | TE10,4 | TEM00 | 0.65 | 53 (SDC) | 0.3 |
Gycom, Russia | 82.7 | TE10,4 | TEM00 | 0.9 | 32 | 0.3 |
Gycom, Russia | 82.7 | TE10,4 | TEM00 | 0.2 | 52 (SDC) | CW |
Gycom, Russia | 84 | TE12,5 | TEM00 | 0.88 | 54 (SDC) | 3.0 |
Gycom, Russia | 84 | TE12,5 | TEM00 | 0.5 (0.2) | 50 (SDC) | 10 (CW) |
Hughes | 60 | TE02 | TE02 | 0.2 | 35 | 0.1 |
IECAS, China | 24.1 | TE01 | TE01 | 0.15 | 24 | 0.02 |
IECAS, China | 34.3(2Ωc) | TE02/03 | TE03 | 0.2 | 30 | 0.02 |
Mitshubishi, Japan | 88 | TE8,2 | TEM00 | 0.35 | 29 | 0.1 |
NEC, Japan | 35 | TE01 | TE01 | 0.1 | 30 | 0.001 |
NRL, USA | 35 | TE01 | TE01 | 0.15 | 31 | 0.02 |
Philips, Germany | 70 | TE02 | TE02 | 0.14 | 30 | CW |
Toshiba, Japan | 77 | TE18,6 | TEM00 | 1.2 | 38 (SDC) | 10.0 |
Toshiba, Japan | 77 | TE18,6 | TEM00 | 0.3 | 36 (SDC) | 900 |
UESTC, China | 70(2Ωc) | TE02/03 | TE03 | 0.1 | 20 | 0.0001 |
UESTC, China | 94(2Ωc) | TE02/03 | TE03 | 0.12 | 20.5 | 0.0001 |
94 | TE61/62 | TE61/62 | 0.09 | 43 | CW |
Gyrotrons for electron cyclotron resonance heating, 28–95 GHz.
SDC: Single-Stage Depressed Collector; CW: Continuous Wave Operation.
Institute | Frequency (GHz) | Mode | Power (MW) | Efficiency (%) | Pulse length (Sec) | |
---|---|---|---|---|---|---|
Cavity | Output | |||||
CPI, USA | 140 | TE02/03 | TE03 | 0.1 | 27 | CW |
CPI, USA | 140 | TE15,2 | TE15,2 | 0.32 | 31 | 3.6 |
CPI, USA | 140.2 | TE28,7 | TEM00 | 0.9 | 33 (SDC) | 1800 |
KIT, Germany | 140.8 | TE03 | TE03 | 0.12 | 26 | 0.4 |
KIT, Germany | 162.3 | TE25.7 | TEM00 | 1.48 | 35 | 0.007 |
KIT, Germany | 139.8 | TE28,8 | TEM00 | 1.0 | 50 (SDC) | 12 |
KIT, Germany | 139.8 | TE28,8 | TEM00 | 0.92 | 44 (SDC) | 1800 |
Gycom, Russia | 140 | TE22,6 | TEM00 | 0.96 | 36 | 1.2 |
Gycom, Russia | 140 | TE22,6 | TEM00 | 0.54 | 36 | 3.0 |
Gycom, Russia | 140 | TE22,6 | TEM00 | 0.1 | 35 | 80 |
Gycom, Russia | 170 | TE25,10 | TEM00 | 1.0 | 53 (SDC) | 570 |
Gycom, Russia | 170 | TE25,10 | TEM00 | 0.8 | 55 (SDC) | 1000 |
Gycom, Russia | 140 | TE22,6 | TEM00 | 0.8 | 32 | 0.8 |
Gycom, Russia | 140 | TE22,6 | TEM00 | 0.88 50 | 50.5(SDC) | 1.0 |
Toshiba, Japan | 170 | TE31,8 | TEM00 | 1.3 | 32 | 0.003 |
Toshiba, Japan | 170 | TE31,12 | TEM00 | 1.56 | 27 | 0.1 |
Toshiba, Japan | 168 | TE31,8 | TEM00 | 0.52 | 19 | 1.0 |
Toshiba, Japan | 168 | TE31,8 | TEM00 | 0.52 | 30 (SDC) | 1.0 |
Gyrotrons for electron cyclotron resonance heating, above 140 GHz.
The authors are thankful to Dr. M.V. Kartikeyan, professor, Indian Institute of Technology (IIT)-Tirupati, India, for his valuable suggestions and inputs. The authors are also thankful to Sri G. Viswam, Center Head, Microwave Tube Research & Development Center (MTRDC), Bangalore, India, for his necessary help and support. Also, the authors are thankful to Shroyonaa Karmakar, Jain University School of Design, for the preparation of the diagrams.
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Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"18",type:"subseries",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11414,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",slug:"arli-aditya-parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",slug:"cesar-lopez-camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",slug:"shymaa-enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]},onlineFirstChapters:{paginationCount:13,paginationItems:[{id:"81566",title:"New and Emerging Technologies for Integrative Ambulatory Autonomic Assessment and Intervention as a Catalyst in the Synergy of Remote Geocoded Biosensing, Algorithmic Networked Cloud Computing, Deep Learning, and Regenerative/Biomic Medicine: Further Real",doi:"10.5772/intechopen.104092",signatures:"Robert L. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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