IL-21-induced apoptosis in U937 leukemia cells and monocytes.
\r\n\tThere are a variety of approaches to reversing biodiversity loss, ranging from economic, to ecological and ethical. The utilitarian approach to conservation, bolstered by the concept of ecosystem services, can be utilized to improve the conservation case by supplementing the burgeoning biodiversity rhetoric. To address this issue, a pluralistic approach to biodiversity is required for conservation and sustainability.
",isbn:"978-1-80356-339-8",printIsbn:"978-1-80356-338-1",pdfIsbn:"978-1-80356-340-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"ab014f8ed1669757335225786833e9a9",bookSignature:"Dr. Gopal Shukla, Dr. Jahangeer Bhat and Dr. Sumit Chakravarty",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11460.jpg",keywords:"Ecosystem Services, Intrinsic Value, Global Trends in Biodiversity Loss, Convention on Biological Diversity, Utilitarian Value, Biodiversity Conservation, Perception, In Situ and Ex Situ Conservation, Nature Conservation, Sustainable Development Goals, Drivers of Degradation, Prioritizing Biodiversity",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 17th 2022",dateEndSecondStepPublish:"April 22nd 2022",dateEndThirdStepPublish:"June 21st 2022",dateEndFourthStepPublish:"September 9th 2022",dateEndFifthStepPublish:"November 8th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Gopal Shukla, prior to becoming an assistant professor, has worked under NAIP (National Agricultural Innovation Project), NICRA ( National Innovations on Climate Resilient Agriculture), and SERB (Science and Engineering Research Board) projects. The focus of his research and development work is forest conservation. He has authored 75 research papers, 10 book chapters and has edited 5 books.",coeditorOneBiosketch:"Dr. Jahangeer is a Guest Associate Editor in Frontiers in the Environmental Science journal and is the first researcher to report the first time growing of Acacia dealbata Link. (Silver Wattle), an invasive species in the high altitudes of the Himalayas. He has 11 years of research and 8 years of teaching experience with a publication record of more than 60, including research articles, review papers, conference papers, and books of national and international repute.",coeditorTwoBiosketch:"Dr. Chakravarty, Ph. D., has a wide experience in forestry training, research, and development. He is currently working as a Professor in Uttar Banga Krishi Viswavidyalaya, Pundibari, Cooch Behar, West Bengal, India. He has conducted research on several aspects of forestry, agroforestry, medicinal plants, and climate change. 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His focus of research is vegetation ecology, ethnobotany, and evaluation of ecosystem services, forest plant biodiversity, climate change, and socio-cultural issues in forestry. Dr. Jahangeer is currently working at the College of Horticulture and Forestry, Rani Lakshmi Bai Central Agricultural University, Jhansi, India.",institutionString:"Central Agricultural University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Central Agricultural University",institutionURL:null,country:{name:"India"}}},coeditorTwo:{id:"94999",title:"Dr.",name:"Sumit",middleName:null,surname:"Chakravarty",slug:"sumit-chakravarty",fullName:"Sumit Chakravarty",profilePictureURL:"https://mts.intechopen.com/storage/users/94999/images/system/94999.jpg",biography:"Dr. Sumit Chakravarty, Ph.D., has wide experience in forestry training, research, and development. 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Subsequently, the investigators identified a specific clone as containing pro-proliferative effects that was sensitive to neutralization by the soluble IL-21R. Later investigators characterized this clone as a factor, which was subsequently renamed IL-21 [2]. The sequence of this new cytokine gene has an open reading frame that encodes for a 163 amino acid peptide, later confirmed as IL-21. Matured IL-21 is 15 kDa and it has four helix bundle cytokine domains and two pairs of cysteine residues showing significant homology to IL-2, IL-4, IL-15 and GM-CSF [2, 3, 4]. Based on these structural characteristics, [1] IL-21 was placed in the IL-2 family. The IL-21 gene is located at chromosome 4q26–27 [1] and found to be approximately 180 kb from the IL-2 gene. In contrast, the human IL-15 gene is located on chromosome 4q31. Clearly, there is some commonality regarding the organization, gene structure, and location of these cytokines [1]. Human IL-21 has 62% homology with murine IL-21 in addition to their two pairs of cysteine residues and well conserved WSEWS motif [5] even though the murine IL-21 gene is located on chromosome 3 [1].
Initial report indicated that IL-21 is produced exclusively by CD4+ T cells during their response to stimulation by anti-CD3 and anti-CD8 antibodies [6]. However, other cell types are known to produce IL-21 [2, 3, 4, 5]. IL-21 has effects on many cell types including human leukemia cells and human monocytes [2, 3, 4, 5, 6, 7]. The IL-21 receptor (IL-21R) is expressed on both CD4+ and CD8+ T cells in which IL-21 stimulates proliferation [1]. In addition, IL-21 promotes allogeneic-specific proliferation of lymph node T cells, enhances cytolytic activity, induces IFN-γ production in T cells [2, 3] and enhances clonal expression of antigen-activated T cells [5, 6]. IL-21 also enhances naïve OT-1 cell response, enhances the affinity of the antigen-specific CD8+ T cells, and regulates the functions of both T cells and B-lymphocytes [1, 6, 7]. It also plays important roles in B cell proliferation, differentiation and class switching [8]. IL-21 causes induction of apoptosis of resting primary B cells via downregulation of anti-apoptotic factors, Bcl-2 and Bcl-xL [9] an effect which differentiates IL-21 from other members of the IL-21 family known to promote proliferative and survival [2, 3, 7, 8].
In B-chronic lymphocytic leukemia cells (B-CLL) IL-21 enhances production of granzyme B, which mediates B-CCL apoptosis when these cells were co-treated with IL-21 and CpG oligodeoxynucleotide [9]. Thus, IL-21 has anti-proliferative effects on B lymphoma cell line [3, 10, 11] suggesting that IL-21 has potential anti-tumor activity against B-cell malignancies. IL-21 enhances transcription of genes that encode IL-21R, and IL-18R, all of which are involved in innate immunity [10, 11, 12, 13]. IL-21 expression is Ca2+-dependent and that the IL-21 gene has three NFAT binding sites, which may be involved in regulation of the IL-21 gene promoter function by calcium ionophore [14]. In contrast to its known anti-proliferative effects [9, 10, 12, 13], IL-21 promotes growth, survival and induces DNA synthesis in human myeloma cell lines via Jak1/STAT2/3 mechanism [12]. In B cells, co-stimulation by IL-21 leads to three effects: growth arrest, apoptosis or growth [12, 13, 14, 15, 16]. Furthermore, IL-21 promotes maturation of NK cells [14], enhances differentiation of NK cells via co-stimulation with either IL-2, or IL-15 or IL-18 and regulates the functions of many different cell types [17, 18, 19, 20].
IL-21 receptor (IL-21R) was first discovered in 2000 [1, 2] by investigators who identified a clone structure from the human chromosome 16p11 that led to their discovery of a protein of 538 amino acids [9]. This protein of 60 kDa was later identified as the type 1 receptor with about 62% homology to the IL-4 receptor (39 kDa) whose gene is located on chromosome 16 [1, 16]. The IL-21R has two subunits, alpha and gamma and it is expressed in B cells, T cells, dendritic cells, NK cells, myeloma cell lines, lymphoma cell lines (IM-9, NK-92 and Jarkat cells), and lymphoid tissues including spleen and thymus in both CD4+ and CD8+ T cells [17, 18]. IL-21R is upregulated upon T cell receptor activation [17, 18]. IL-21R is also expressed and upregulated in epidermis of systemic sclerosis patients [18]. IL-21R has two pairs of conserved cysteine residues in its extracellular domain and a WSXWS motif proximal to its transmembrane domain. In addition, it has two Box 1 and 2 motifs, which serve as docking sites for cytoplasmic Jak kinases involved in transducing cellular signaling from the IL-21R [21, 22, 23, 24, 25]. The γ-chain of IL-21R is an essential component of the IL-2 family of receptors that is critical for signaling as anti-γc antibodies blocked B cell proliferation induced by IL-21 and CD40, indicating that the gamma chain is involved in IL-21R signaling mechanisms [25, 26]. Furthermore, the Jak inhibitor WH-P131 blocked IL-21-induced proliferation of BaF3 cells via IL-21R confirming a role for Jak3 in IL-21R signaling. In addition, inhibition of the IL-21γc subunit by monoclonal antibody blocked IL-21-induced activation of Jak1, Jak3, and STAT1, STAT2, STAT3 and STAT5 thus further supporting a critical role for IL-21 γc subunit in IL-21 signaling [26].
IL-21R associates with BCL-6 translocation in B cell lymphomas and expression of IL-21R is upregulated by CD40 leading to transduction of pro-apoptotic signals [27, 28]. In addition, IL-21R plays important roles in immunoglobulin production and decreased in IL-21R expression is associated with decline in normal antibody production [28]. Furthermore, there is a decrease in IL-21R expression on B-lymphocytes in patients with systemic lupus erythromatosis (SLE) [29]. IL-21 synergizes with IL-15 to induce expansion of NK cells [1] and synergizes with IL-15 and IL-18 to upregulate IFNγ mRNA synthesis and production in NK and T cells. IL-21 also synergizes with IL-15 to promote proliferation of memory and naïve CD8+ [18], Furthermore, IL-21 has positive effect on tumor regression in B16 melanoma cells [24] as well as synergizes with IL-15 to delay CD11b bone marrow cell apoptosis [30]. In addition, IL-21 augments proliferation of IL-6-dependent human myeloma cells expressing IL-21R and synergizes with TNF to enhance myeloma cell mitogenesis [3, 13]. These synergistic effects of IL-21 led to consideration of IL-21 as a potential therapeutic agent for many cell malignancies [30]. In contrast to its synergetic effects, IL-21 antagonizes IL-4’s ability to induce isotype switching in B cells from IgM to IgG and inhibits IFN-γ production by Th1 cells an [31, 32].
In BAB/C mice undergoing immunization, IL-21 caused reduction in antigen-induced eosinophil recruitment into the airway of the mice without affecting antigen-induced lymphocyte and macrophage recruitment [30]. However, another study [33] showed that IL-21 causes a decrease in antiovabumin IgE and IgG production, implying that IL-21 has anti-inflammatory effects in asthmatic patients and could serve as a potential therapy against asthma. The role of IL-21 in Crohn’s disease (CD) has been reported [34]. Since Steven Rosenberg and his team [35] reported that IL-2 has anti-tumor in cancer patients, there has been extensive interest on whether members of IL-2 family of cytokines could generate similar effects. Subsequently, there are many reported that IL-21 alone or in combination with other cytokines produces anti-growth effect in various animal cancer models and on a variety of solid tumors including tumors without IL-21R [11, 36]. IL-21 is essential for IFN-γ induced expression of CXC chemokines, known to inhibit tumor angiogenesis. In addition, IL-21 induces tumor rejection by specific CTL and IFN-γ-dependent CXC chemokines in synergistic manner [37]. This anti-tumor effect of IL-21 is independent of the systemic cytokine release by known inflammatory mediators like IFN-y, IL-4, IL-10 and IL-12 [38]. Either alone or in combination with IL-23, IL-21 exhibits strong anti-tumor and anti-metastasis effects in kidney renal cell carcinoma in BALB/C mice and in human esophageal carcinoma tumors [39, 40]. Similarly, combination treatment with IL-15 and IL-21 promoted nearly 100% rejection of head and neck squamous cell carcinoma (HNSCC) in 30% of the experimental animals [41, 42], indicating potential role of IL-21 and IL-15 in minimizing transfection of animals with HNSCC [41, 42]. Similar reports in metastatic lymphoma animal models have indicate that IL-21 can act with other cytokines in combination therapy in the treatment of metastatic lymphoma tumors [43]. IL-21 enhances the synthesis of MIP-3α, a T cell chemoattractant and induce chemotaxis in intestinal epithelial cells (HT-29), indicating that IL-21 enhances immune cell response and could serve as an effective addition to cancer immunotherapy [43, 44, 45].
Our rationale for examining IL-21 effects in human myeloid monocytic leukemia cells and monocytes was based on the observations that IL-21 plays relevant roles in many types of cancer including solid tumors and lymphoma [36, 37, 38, 39, 40, 41, 42, 43, 45]. However, little is known about the biologic effects of IL-21 in leukemia cells. In addition, while the signaling pathways of IL-21 in many cell types are known, not much is known about the signaling pathway utilized by IL-21 in leukemia cells and monocytes. Furthermore, knowledge on potential cytokine induction ability of IL-21 in leukemia cells and monocytes was lacking. Our earlier preliminary report indicates that STAT3, Smad1, Smad2, and Smad3 are regulated by IL-21 in U937 leukemia cells [46]. Additionally, IL-21 activates Jak/STAT and MAPK pathways in different cell types [47]. Therefore, the main purpose of our study was to determine the biological effects of IL-21 in human U937 leukemia and monocytes and to gain more insight into whether the Jak/STAT and MAPK-signaling pathways mediate IL-21’s specific biologic effects in these cells.
U937 myeloid monocytic leukemia cells were obtained from ATCC and cultured in RPMI-1640 media containing L-glutamine and supplemented with 10% heat-inactivated fetal bovine serum (FBS) (Atlanta Biological. GA) in the presence of 5 U/ml penicillin +50 U/ml of streptomycin (Invitrogen, CA). The cultures were maintained in 5% CO2 at 37°C and 100% humidity. HeLa/STAT3-luc cells were created by co0transfection of pSTAT3-luc and pHygromycin into human cervical epithelial HeLa cells. These cells were maintained in the same culture in the presence of 100 μg/ml of hygromycin B (Roche, NJ) [7].
Human PBMC were isolated from anonymous health individuals (NY Blood Center, Long Island, NY) by Ficoll gradient centrifugation at 400 ×
Sixty million (6 × 106) U937 leukemia cells or monocytes were untreated (control) or treated with IL-21 (50 or 100 ng/ml) in a time course (2, 5, 15, 30, 60 minutes) experiments [48, 49]. At the end of the time course, the cells washed 2× with PBS and collected as pellet by centrifugation at 1800 rpm for 3 minutes. The cell pellets were washed two times with cold PBS and lysed in 500 μl of lysis buffer A (containing protease inhibitors, 0.5% Triton X-100, 50 mM NaF and 2 mM Vanadate) as described in [7]. Total cell lysate protein concentration was determined by Coomassie Blue Protein Assay Kit (Pierce, IL). Equal amount of lysate proteins (120 μg per sample) was resolved by 12% polyacrylamide gel electrophoresis followed by transfer of the proteins to membrane and blotted against specific antibodies to total Jak2 or Jak3 or Tyk2 or p-Jak2 or p-Jak3 or p-Tyk2 as previously described [7]. The immunoblot band intensities were scanned via spot densitometry analysis for quantitation and scanned intensity values from the IL-21 treated samples were compared to the intensity in the untreated samples.
Twenty million cells (20 × 106 cells) untreated or treated with 50 ng/ml of IL-21 for 24 hours were lysed in lysing buffer and protein the concentration was determined by Coomassie Blue protein determination assay kit [50]. Exactly, 200 μg/lane of total cell lysate was separated by 15% polyacrylamide gel electrophoresis and the proteins were subsequently transferred to nitrocellulose membrane. Following blocking of the background on the membrane, for detection of IL-21R, the nitrocellulose membranes containing transferred protein bands were incubated with 1:1000 dilution of IL-21 receptor primary antibody (Novus Biologicals) at 4°C in blocking buffer (TBS, 0.1% Tween 20, 5% nonfat dry milk) for 1 hour. Next, the membrane was washed 3x in water and incubated in milk blocking buffer containing 1:3000 dilution of goat anti-rabbit IgG HRP antibody (Amersham, CA) for 1 hour at room temperature. This was followed by washing with TBS buffer containing 0.5% Tween 20. Finally, the membrane was incubated for 1 minute with enhanced chemiluminescence (ECL) solution and exposed to Kodak film and band intensities were scanned via spot densitometry analysis.
To detect Jak1 by ELISA, 96 well plates were pre-coated with 10 μg/ml poly lysine for 30 minutes [51]. U937 cells were seeded at 20 × 103/well in 96 well plates and incubated in serum free medium overnight. Subsequently, the cells were either untreated or treated with 50 or 100 ng/ml of IL-21 for 2, 15, 30 or 60 minutes followed by rapid removal of the culture medium by aspiration. The cells in the wells were fixed with 100 μl of 8% formaldehyde in PBS for 20 minutes at room temperature. After removal of the formaldehyde all the wells were washed three times with 200 μl of wash buffer (0.1% Triton X-100 in PBS). After washing, 100 μl of quenching buffer (wash buffer with 1% hydrogen peroxide and 0.1% azide) was added to each well and incubated for 20 minutes at room temperature. Then, the wells were washed two times with wash buffer followed by incubation of the wells with 100 μl of antibody blocking buffer for 1 hour at room temperature. After removal of the antibody blocking buffer the wells were washed with 200 μl wash buffer followed by addition in 40 μl of diluted specific p-Jak1 or total Jak1 antibody. The wells were covered with parafilm, and incubated overnight at 4°C. The primary antibodies were removed by aspiration, and wells were washed three times with wash buffer. Next, 100 μl of diluted secondary antibody (goat-anti-rabbit HRP) was added to each well and incubated for 1 hour at room temperature with head-to-tail shaking. After the incubation, the secondary antibody was removed and wells were washed three times with wash buffer and once with PBS. The wells were aspirated to remove all traces of liquid, and 100 μl of developing solution was added to each well. The wells were incubated for 15 minutes at room temperature, while monitoring the color development. Thereafter, 100 μl of stop solution was added to each well. Lastly, absorbance was read at 450 nm using a microtiter plate reader. Experiments were conducted in triplicate.
To determine whetherIL-21 induces activation of STAT proteins, untreated and IL-21 treated U937 leukemia cells from time course experiments for specific STAT/DNA binding assays using the STAT transcription factor assay kits (Active Motif, Chemicon) [52, 53]. Following stimulation of cells with IL-21, we used the kit to monitor the activation or repression of several STAT proteins. The experiments were performed in triplicate.
U937 cells (1 × 106) were either untreated or treated with 50 ng/ml of IL-21 for 24 or 48 hours [54, 55]. The cells were packed by centrifugation at 325 ×
To determine whether IL-21 stimulates cell proliferation in U937 cells, 6 × 106 cells were either untreated or stimulated with 100 ng/ml of IL-21 for up to 48 hours [56]. The cells were harvested at 24 or 48-hour time point. Aliquots of the harvested cells from each time point were diluted into 0.4% trypan blue/PBS solution at a ratio of 1:10. The cells were counted in triplicate and the average was recorded as the cell number for each sample. To validate the results of the trypan blue cell proliferation assay we performed MTT assay. Briefly, 6 × 106 cells were untreated or treated with 100 ng/ml of IL-21 for 24, 48 or 72 hours in 96 well plates. Next, we added 100 μl MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) to each of the wells. The plates were incubated at 37°C to permit reduction of the MTT by the electrons from the viable cells. Four hours later, the MTT formazan produced in wells containing live cells appeared as black, fuzzy crystals at the bottom of the wells. Next, we added isopropanol and HCl (100 μl) to each of the wells and mixed thoroughly. After 1 hour, the absorbance of stable blue color developed in the upper phase of the cell pellets (indicative of cell viability) was measured in a microplate reader at 750 nm.
To determine whether IL-21 induces apoptosis in human U937 leukemia cells and human monocytes, we performed caspase9 and caspases3 enzymatic (colorimetric) assays in cell lysates from untreated and IL-21 treated cells. Leukemia cells (10 × 106) and human monocytes (10 × 106) were pretreated with orthovanade (5 mM) for 30 minutes [57, 58, 59]. The cells were either untreated or treated with 100 ng/ml of IL-21 for 24 or 48 hours. The cells were lysed in RIPA buffer, and total lysate protein concentration was determined as indicated above. To assess the lysate for caspases activities, 20 μg total lysate protein from each sample was added to each experimental assay well. For positive caspase activity, we used 20 μg of total cell lysates from U937 or monocytes treated with sodium butyrate, which is a strong inducer of apoptosis. Caspase9 and caspases3 activities were measured using specific assay kits (MBL International, Woburn, MA) using specific substrate (p-LEHD conjugate) for caspases9 and caspases3 (DEVD-pNA) respectively. The absorbance was read at 405 nm with microplate reader.
To determine whether culture medium from IL-21 causes chemotaxis, we placed culture media from untreated U937 cells or from U937 leukemia cells treated with IL-21 for 24 hours in the lower chamber of the Boden Chamber to serve as chemoattractant [60]. Human monocytes ((2 × 105) suspended in RPMI medium) were placed in the upper chamber. After 2-hour incubation in the Boyden Chamber, monocytes in both the lower and upper chambers counted as instructed by the kit supplier.
To determine whether IL-21 modulates Stat3 promoter function, we performed STAT3-Reporter gene analysis [61, 62]. STAT3-Reporter HeLa stable cells (Panomics, CA.) placed in 96 well plates for overnight incubation. The cells were either untreated or stimulated with different concentrations of IL-21 for different time points up to 24 hours. In some cases the cells were stimulated with different concentration of IL-21 (0.2, 5, 10, 12.5, 50, 75 or 100 μg/ml) for to 8–24 hours. As a positive control for the STAT3-Reporter gene activation, we treated some of the cells with Oncostatin M (Sigma, St. Louis) separately. At the end of the treatments, the medium was aspirated and the cells washed two times with PBS. The cells from each well were lysed in 100 μl lysing buffer and equal amount of protein in 20 μl of the lysate were added to 100 μl of Luciferase Assay Reagent (Promega) and the luciferin expression (as indicated by light production) was measured with a TD-20/20 luminometer.
To determine whether IL-21 stimulates cell proliferation in myeloid monocytic leukemia cells, we performed proliferation assays on untreated and IL-21 treated leukemia cells. As shown in Figure 1a, IL-21 does not stimulate cell proliferation in human U937 myeloid monocytic leukemia. These cells express IL-21R. Therefore, it was surprising that IL-21 did not promote proliferation as indicated by the outcomes of both the trypan blue and MTT assays in cells treated with IL-21 for up to 48-hours. Furthermore, our results from cell cycle analysis (Figure 1b) show that IL-21 does not promote cell cycle progression during a 48-hour treatment. In contrast, IL-21 enhances accumulation of the leukemia cells at G0/G1 phase (Figure 1c), suggesting IL-21-induces apoptosis in the leukemia cells. This observation was validated by the results from specific caspase9 (Figure 2a and b) and caspases3 enzymatic assays (Table 1). As can be seen, IL-21stimulates several fold activation of both caspases9 and caspases3 activities in the IL-21 treated U937 cells. IL-21 produced far less apoptotic effect in monocytes as compared to the control (untreated) cells. The ability of IL-21 to stimulate apoptosis shown here is similar to an earlier reportin B cells [17].
(a and b) Effects of Il-21 on U937 leukemia cell growth.
(a) Effect of IL-21 on cell cycle progression. (b) IL-21-induced apoptosis in U937 leukemia cells. Asterisk (*) indicates significant difference between IL-21 treatment cells and untreated cells. (c) IL-21-induced apoptosis in monocytes. Asterisk (*) indicate significant difference between IL-21 treatment cells and untreated cells.
Experimental condition | U937 cells Caspase3 | Monocytes Caspase3 |
---|---|---|
(fold activation) | (fold activation) | |
Untreated | 1 | 1 |
Cells + IL-21 (24 hours) | 5.3 | 2.0 |
Cells + IL-21 (48 hours) | 8.2 | 2.5 |
IL-21-induced apoptosis in U937 leukemia cells and monocytes.
IL-21-Induced apoptosis in U937 cells and human monocytes. Leukemia cells (1 × 106) Or monocytes (1 × 106) were untreated (UT) or treated with 100 ng/ml of IL-21 for 24 or 48 hours and cell lysate from each experiment was assayed for caspase3 activity. Data represents an average of two experiments.
In our earlier reports [7, 46] we should that in both U937 leukemia cells and monocytes, IL-21 promoted time-dependent differential expression of several cytokines in the order of induction: IL7 > IL-15 > IL-2, IL-1, IFN-γ, TGFβ > GM-CSF and chemokines in the order: IL-8 > RANTES, IP-10 > MIP-1a > Eotaxin. Similar results were found in monocytes although to different extent. Furthermore, IL-21 triggers rapid phosphorylation of ERK-1/2 between 2 and 60 minutes in both leukemia cells and monocytes. IL-21-induced ERK1/2 phosphorylation is associated with ERK-1/2 enzymatic activation. The stimulatory effect of IL-21 on ERK-1/2 activation is significantly blocked by a neutralizing antibody against the IL-21R or impartially inhibited by the MEK inhibitor U0126 [7]. These results show that IL-21-induced interleukin and chemokine expression is partially mediated by ERK-1/2-dependent pathway.
Next, we investigated whether IL-21 activates specific members of the Jak/Stat signaling pathway. Cell lysates from untreated cells or IL-21 stimulated cells were analyzed by Western Blot analysis using monoclonal antibody against specific members of the Jak/Stat signaling pathway. In some cases, we performed ELISA assay using specific ELISA assay kit (Ray Biotech Life, Peachtree Corner, Georgia, U.S.A) for specific members of the Jak/Stat signaling pathway [48, 49, 51, 63]. Our results (Figure 3) indicate IL-21 causes differential activation of the Jak kinases. Notably, Jak1 and Jak2 are rapidly activated in response to IL-21 stimulation; maximum stimulation occurring within 2–5 minutes. Even though Jak3 and Tyk2 are also activated in response to IL-21, the effect is delayed with maximum stimulation by IL-21 occurring at between 15 and 60 minutes. Because IL-21 stimulates significant activation of the Jak kinases, we examined whether specific members of the Stat family are also activated downstream of the Jak kinases. As shown (Figure 4), IL-21 differentially activates specific members of the STAT family. The order of activation was STAT2 > STAT4 > STAT6 > STAT3>. Clearly, IL-2 does not activate STAT1 and STAT5. In order to determine whether Jak2 and or Jak3 is responsible for activating Stat3 and Stat4, we examined the effect of Jak2 inhibitor and Jak3 inhibitor on STAT3 and STAT4 activation. Our results (Figure 5) show that in the presence of the Jak2inhibitor, there is significant decline in both STAT3 activation. Clearly, our results show that both Jak2 and Jak3 are responsible for STAT3 activation [63]. In contrast, the Jak2 inhibitor and Jak3 inhibitor were only slightly effective in inhibiting STAT4 activation. Hence, our results suggest Jak2 and Jak3may be involved in activating STAT3 [63]. These observations led us to conclude that, Jak2, Jak3 and STAT3 may be relevant for IL-21 induced signaling in leukemia cells and monocytes [63, 64].
(a) Effect of IL-21 on Jak1 activation. (b-d) Time course of IL-21-induced differential activation of Jak2, Jak3 and Tyk2.
IL-21 differentially activates STAT1, STAT2, STAT3, STAT4, STAT5 and STAt6.
Effect of Jak2 and Jak3 inhibitors on IL-21-induced STAT activation. Asterisk (*) indicates significant difference between IL-21 treatment alone and either IL-21 treatment in the presence of Jak2 inhibitor or Jak3 inhibitor.
In our previous report, we showed that IL-21 stimulates differential induction of cytokine and chemokine expression [7, 40] and that the effect is partially dependent on ERK1/2. Given that some of the chemokines including RANTES, MIP-1α could induce chemotaxis, we determined if the ERK-1/2 and Jak/Stat signaling pathways contributes to induction of chemotaxis. Therefore, we examined the effect of pre-incubation of cells with either ERK1/2 inhibitor or Jak2 inhibitor or with both prior to stimulation of the cells with IL-21 and assayed the cells for chemotaxis. The results (Table 2) confirmed that both the ERK1/2 and Jak2 contribute significantly towards IL-21-induced chemotaxis, suggesting that both pathways also contribute to IL-21-induced cytokine and chemokines expression. Thus, IL-21 utilizes both the ERK-1/2 MAPK and Jak/Stat signaling mechanisms for transducing its signal downstream the IL-21R. Perhaps, applications of anti ERK-1/2 and anti-Jak kinases agents could be relevant in blocking unwanted IL-21 effects in leukemia patients.
Experimental condition | Chemotaxis (fold change) |
---|---|
Untreated | 1 |
Cells + IL-21 | 6.3 ± 0.2 |
Cells + U0126 + IL-21 | 3.5 ± 0.3 |
Cells + AG490 + IL-21 | 2.5 ± 0.1 |
Cells + U0126 + AG490 + IL-21 | 1.3 ± 0.1 |
Cells + U0126 | 0.9 |
Cells + Ag490 | 0.8 |
Evidence of involvement of ERK-1/2 and Jak2 in IL-21-induced chemotaxis.
Evidence of involvement of ERK-1/2 and Jak2 in IL-21-induced chemotaxis. U937 leukemia cells were either untreated (UT) or treated with 100 ng/ml of IL-21 in the presence of either MEK inhibitor (U0126) or Jak2 inhibitor (AG490) or with both inhibitors. The effect of the each inhibitor alone was determined. Cells were incubated for 8 hours and culture medium from each experiment was placed in the bottom insert to serve as chemoattractant to monocytes (2 × 105) placed in the upper cup for Boyden Chamber chemotaxis assay. Data represents the mean plus SD from three experiments.
After showing that IL-21 regulates STAT3 phosphorylation and its DNA binding activity, we were curious whether IL-21 is capable of regulating the STAT3 promoter function. To address this question, we used a construct containing the STAT3 promoter cloned upstream the Luciferase gene (pSTAT3-Luc) in HeLa cells from human cervical cancer epithelial cells. We allowed cells to recover overnight and divided them into equal number of cells. The cells were either untreated or treated with different concentrations of IL-21 in time course experiments up to 24 hours. Luciferase assay was performed to determine the reporter gene function [61, 62]. The results in Figure 6 indicate IL-21 induces a 2.5-fold increase in Luciferase activity in IL-21 treated cells as compared to untreated cells. From these results, we conclude that in addition to posttranslational regulation of STAT3, IL-21 is able to activate STAT3 promoter function. In addition, to STAT3 promoter regulation, we also noted that IL-21 regulates activation of several transcriptional factors including AP-2, Smad3 and 4, Pax-5, C-Myc, MEF-1 and CRE [46] that the effects of IL-21 were partially dependent on STAT3 activation since siRNA knockdown of STAT3 led to inhibition of IL-21’s effects. By activating these transcriptional factors, IL-21 has broader regulatory roles that will likely impact on expression of genes downstream of these transcriptional factors with potential implicating consequences on the biology of different cell types.
Effect of IL-21 on STAT3 promoter cloned upstream of luciferase gene in STAT3-reporter-stable Hela cells. Asterisk (*) indicates significant difference between IL-21 treatment cells and untreated cells.
We have provided strong evidence that IL-21 does not promote proliferation in U937 myeloid monocytic leukemia cells. We have made nearly similar observations in THP-1 and HL-60 leukemia cell lines. However, IL-21 strongly promotes apoptosis in leukemia cells as has been reported for B cells [58]. In contrast, monocytes are somehow resistant to the apoptosis inducing effects of IL-21. These results are novel and could have interesting clinical implications and applications. Activation of caspases9 and caspases3 by IL-21 reported here, could point to involvement of either extrinsic or intrinsic apoptotic pathway or both and warrant further investigation. Currently, studies are underway to elucidate the potential involvement of mitochondrial in the mechanism of IL-21-induced apoptosis in these cells. Based on its ability to induce apoptosis in leukemia cells while sparing monocytes, IL-21 could be considered as potential anti-leukemia agent to kill myeloid monocytic leukemic cells [58, 59] or in combination with pro-apoptotic agents such as butyrate [65]. Likewise, a combination therapy of IL-21 with other cytokines such as IL-34, which promotes monocyte-like differentiation in leukemia cells, could be beneficial as anti-leukemia agent [66]. The stimulatory role of IL-21 in chemotaxis and invasion of cancer cells could be explored for development of anti-IL-21 drugs to combat IL-21-mediated invasive cancers as previously suggested [67, 68, 69].
In both leukemia cells and monocytes, IL-21 induces differential expression of IL-2, IL-7, IL-15, GM-CSF, TGF-β and IFNγ, which are known to regulate diverse cell functions. IL-15 is an effective immunotherapy in conjunction with IL-2. TGF-β induction by IL-21 is also very important since TGF-β is a regulator of cell growth and differentiation in many different cell types. GM-CSF is a promoter of colony formation during bone marrow hematopoietic differentiation as well as a stimulator of specific cell-mediated cytotoxicity against tumor targets. IFNγ and IL-7 are both relevant for regulation of cellular functions [7]. Thus, some of the effects can be beneficial in promoting immune defense in organisms in response to infection by pathogens.
The chemokines including IL-8, RANTES and MIP-1α, secreted to the microenvironment by leukemia cells and monocytes in response to IL-21 in leukemia could trigger of chemotaxis [7] as well as mediate cell–cell communication [70]. The inflammatory and pro-inflammatory cytokines and chemokines produced in response to IL-21 could enhance anti-body secretion and inflammatory responses [71, 72], as well as promote inflammatory diseases including arthritis and SLE [71, 72, 73, 74]. Many of the cytokines induced by IL-21 in these cells could be relevant for immunotherapy. In effect, IL-21 could emerge as an effective adjunct immunotherapy for many types of cancer via T-cell activation, thus leading to increasing cytotoxic effects of NK cells [29]. However, we should not overlook the possibility that some of the cytokines and chemokines induced by IL-21 could alter the tumor microenvironment, enhance NK cell antitumor activity against MHC Class-I-deficient tumors, enhance protection against enteric microbial infections, mediate radiation-improved IL-21 cancer therapy, promote major oncological applications and triggering detrimental side effects including inflammation in cancer patients and Crohn’s disease [74, 75, 76, 77, 78, 79, 80].
Our study was first to provide evidence that activation of the Raf-MEK-MAPK pathway by IL-21 is relevant for some of the biological effects of IL-21 in leukemia cells and monocytes [7]. As shown, IL-21 induces rapid activation of ERK1/2, an effect, which can either be blocked by a neutralizing antibody against the IL-21R or by the MEK inhibitor U0126. Furthermore, our study outcomes suggest that inhibition of ERK-1/2 leads to significant reduction of IL-21-induced cytokine and chemokine expression in leukemia cells and monocytes. However, inhibition of ERK-1/2 by the MEK inhibitor U0126 only partially abrogated IL-21-induced cytokine and chemokine expression, suggesting involvement of signaling pathway (s) independent of Raf-MEK-ERK-1/2.
The Jak/STAT signaling pathway plays major roles in the mechanisms of regulation of cellular functions. Therefore, we examined whether specific members of this pathway are activated by IL-21 in leukemia cells. Our results show that IL-21 activates Jak2, Jak 3 and Tyk2, which are involved in activating several STAT proteins including STAT2, STAT3, STAT4 and STAT6 in both U937 leukemia cells and human monocytes. Using pharmacological inhibitors specific to either Jak2 or Jak3, we found that Jak2 and Jak3 play critical roles in mediating phosphorylation and activation of STAT3. Furthermore, the induction of chemotaxis by IL-21 is dependent on activation of both ERK-1/2 and Jak2. Our study also revealed that IL-21 activates Jak1 and Tyk2 as well as STAT1, STAT2 and STAT4 similar to earlier reports [71, 72, 73, 74, 75]. Taken together, both the Raf-MEM-ERK1/2 and Jak/STAT signaling pathways mediate IL-21-induced cytokine and chemokine expression in leukemia cells and monocytes. However, we are yet to elucidate the roles of STAT1, STAT2 and STAT4 in the biological effects of IL-21 in leukemia cells and monocytes. It remains possible that some of these STAT proteins activated by IL-21 in these cells will have opposing roles as reported in CD+ T cells [75].
The involvement of both the Raf-MEK-ERK and Jak/Stat signaling pathways in mediating signaling from the IL-21R and receptors of IL-2 and IL-15 is well documented [76, 77]. However, our results were among the first to clearly implicate both of these two signaling pathways in the mechanism by which IL-21 induces expression of cytokine and chemokines in leukemia cells and normal monocytes. These observations are interesting in view of the fact that both of these two signaling pathways support cell survival and proliferation and yet IL-21 fails to promote proliferation in the leukemia cells. Additionally, we have shown that IL-21 activates the STAT3 promoter suggesting that genes including anti-apoptotic and pro-apoptotic genes with STAT3 promoter can be regulated by IL-21 in leukemia cells. In addition, IL-21 regulates other transcriptional factors including Smad3/4, AP-2, Pax-5, C-myc, MEF-1 and CRE via partial STAT3-dependent mechanism. As illustrated by our model (Figure 7) upon binding to its receptor, IL-21 activates multiple signaling pathways, which are critical to the observed IL-21’s biological effects in leukemia cells and monocytes.
Proposed signaling model for IL-21 in leukemia cells and monocytes.
The potential for IL-21 to play a role in immunotherapy including its role in cancer therapy is extensively documented [77, 78, 79, 80, 81, 82]. Our work points to the need to expand research on IL-21 in different leukemia cells with the anticipation that the outcomes will provide new ideas for exploring IL-21 in combination therapy for leukemia. Lastly, we propose that targeting the major pathways modulated by IL-21 could lead to new opportunities for treating leukemia.
Our findings indicate that both U937 leukemia cells and human monocytes express IL-21R. In these cells, IL-21 induces differential expression of various cytokines and chemokines and promotes chemotaxis. These biological effects of IL-21 could be associated with either negative clinical implications or positive clinical applications in leukemia patients. The Raf-MEM-ERK1/2 pathway and the Jak-STAT pathway play critical roles in induction of cytokine and chemokine expression by IL-21. Activation of the Jak2 and STAT3 is germane to these effects. Furthermore, IL-21 activates apoptosis in U937 leukemia cells with little or no apoptotic effect on human monocytes. The inability of IL-21 to induce apoptosis in human monocytes while inducing significant apoptosis in leukemia cells could form the basis for future application of IL-21 as a potential therapeutic factor for various types of leukemia. Lastly, the ability of IL-21 to regulate the STAT3 promoter function suggests that genes including pro-apoptotic or anti-apoptotic genes with STAT3 promoter sequences are likely to be modulated by IL-21.
This work was supported by research funds from NIGMS/NIH SCORE, 5T32HL007735, Meharry-VICC Cancer Partnership NCI U54 grant (U54 CA091408) and current Meharry-VICC-TSU NCI U54 grant (5U54CA163069) to Professor Samuel E. Adunyah (SEA). In addition, SEA was supported by NIMHD MeTRC U54 grant (U54MD007593-09) during the preparation of this manuscript. Fuqua was supported by 5T32HL007735 from NHLBI/NIH. We are also grateful to Dr. J. O Price of Vanderbilt VA for flow cytometry work and to Ms. Ketia Barnes and Mrs. Marian Asmah-Addai for Admin support.
MATLAB represents a programming language that is used for designing, simulating and testing of different technical systems [1]. This chapter provides examples of Bluetooth low energy (BLE) applications implemented in MATLAB. In this section, the main aspects regarding developing a BLE MATLAB application are presented. First of all, basics about BLE technology are presented [2, 3, 4, 5]. BLE means exchange data between two or more devices by radio waves over short distances. Mainly, a BLE device can be scanner or advertiser. The advertiser signals its presence by sending its name and address. The scanner finds advertiser devices and can connect to one or more of them. Then the advertiser becomes a server and can send data to the scanner which is now a client. According to BLE architecture, the server can offer services to the client. Some examples of services are battery service, accelerometer service and heart rate measurements. Each service contains more characteristics. The most important attribute of a characteristic is its value, which in general represents sensor data. In addition, a characteristic has one or more of the following properties: read, write and notify.
Starting with 2019b release, MATLAB has introduced a set of functions that allow a simple implementation of BLE application [6]. The minimum setup involves a laptop having an embedded BLE adaptor or a desktop having an USB BLE adapter and some BLE compatible devices.
Scanning for BLE devices can be done using
Using
It can be seen that three BLE devices have been discovered. The connection with Keyfobde99 is achieved, and b1 is a
A part of services and characteristics of a
A characteristic can be accessed either by service name and characteristic name or by service universal unique identifier (UUID) and characteristic (UUID) [6]. According to the information from Figure 2 it can be seen that only the second option can be used because there are more Custom services or characteristics. Furthermore, there is no information about the functionalities of these services or characteristics. Therefore, to start the application, some information is necessary that can be obtained using another application such as BLE Device Monitor [7] or just Wikipedia [8]. Thus, Table 1 presents service name and characteristic name among to UUID for a part of the positions of Figure 2.
Service Name | UUID | Characteristic Name | UUID |
---|---|---|---|
Accelerom. service | FFA0 | Accelerometer enable | FFA1 |
Accelerometer range | FFA2 | ||
Accelerometer X coordinate | FFA3 | ||
Accelerometer Y coordinate | FFA4 | ||
Accelerometer Z coordinate | FFA5 | ||
Period of Reading accelerometer data | FFA6 | ||
Temperature | FFA7 |
UUID for a service and its characteristics.
In order to access a characteristic, the
Using the
Another powerful features is
Create the callback function.
Each of the following sections contains an introduction where the basic function of the program is presented, which is then followed by the program and the results, mainly in graphical form.
This section presents a MATLAB application that uses three temperature sensors. CC2541 Keyfob [9] is a BLE compatible device that contains an accelerometer. Among its basic function, the accelerometer contains an 8-bit temperature sensor. To access the temperature sensor the accelerometer must be enabled first and then the temperature characteristic can be accessed according to Table 1. The period of reading temperature is 3 sec. according to the author publication [10].
At the beginning of the program a general scanning is executed and if none of the desired sensors are discovered the application is stopped through a suitable message on the screen. To do this, accessing the elements of a variable of table type,
Then, depending on the discovered number of sensors, which can be from one to any number (three in this application) the application gets temperature from them and displays it on a graphic. For this purpose, two structures,
The structure of the program is presented below.
%%%%%Key-fob devices%%%%%%%%%%%%%%%%%
The program runs in an endless loop and displays the last 20 values of the three temperatures in a MATLAB figure as in Figure 5. To stop the program, simply close the figure. In addition, the current date and time is displayed on the figure. One of the CC2541 Keyfob was on the outside sill of the window and therefore the resulting temperature was about 5 degree Celsius.
The temperatures from the three sensors.
This section presents a MATLAB application that accesses the accelerometer of the CC2541 Keyfob to read the 8-bit accelerations corresponding to the three axes. The program is similar to that of the previous section. There are also three callback functions, one for each axes. The period of reading data is set to 100 ms.
The program runs in an endless loop and displays the last N=200 samples of each the three axes. Figure 6 presents a screenshot during the running of the program. During this time CC2541 Keyfob was moved such as one of the three axes was on the direction of gravitational force. Thus, most of the time one of the three axes has the absolute value close to g=9.81 m/s2 while the other two are close to zero.
The variation of the three accelerations.
This section presents a MATLAB application that accesses the movement sensor of the device called CC2650 Sensor Tag. This movement sensor contains an accelerometer, a gyroscope and a magnetometer. If the accelerometer of the CC2541 Keyfob which was presented in the third section generates 8-bit data, all of the three sensors of CC2650 Sensor Tag generates 16-bit data.
The gyroscope is a three axis sensor that measures the angular rate,
Thus, Eq. (1) can be implemented by trapezoidal method by using samples of
where
This angle is considered in comparison with the initial position of the gyroscope which is unknown. Using the integration, it generates an error because the gyroscope has an offset. That means its output is different to zero when the gyroscope is still. Thus, by integration it follows that the angle is changed. Therefore this offset must be removed [11].
The magnetometer measures the magnetic field. Thus, if there are no other fields, it measures the magnetic field of the earth. When the magnetometer is placed horizontally, it can measure the angle from the north,
where
and
where
and
while
Regarding BLE, CC2650 Sensor Tag offers more services. The service that allows accessing the accelerometer, the gyroscope and the magnetometer has three characteristics, as shown in Table 2, where also the UUID can be seen. The first one is used to read data. The second one is used to enable the sensors. Each axis of the gyroscope and accelerometer can individually be enabled while the magnetometer can be enabled only for all axes. The third characteristic allows to establish the period of data reading. The data is presented as an 18 bytes string, where each sensor has a field of 6 bytes, two bytes for each axis, in the order: gyroscope, accelerometer and magnetometer. Actually UUID contain more digits but only the different part is presented in Table 2 [8].
Service Name | UUID | Char Name | UUID |
---|---|---|---|
Movement | F000AA80 | Data | F000AA81 |
Configure sensors | F000AA82 | ||
Period | F000AA83 |
UUID for the movement service and its characteristics.
Because in this case the MATLAB programs are much longer than previous ones only some parts of the achieved programs are presented. Mainly, such a program has three parts:
the first part when the sensor is still for a time while gyroscope data are gathered to compensate its offset; generally in this part 200 samples are acquired;
the second part when the sensor is rotated with 360 degrees in both senses around z axis while the magnetometer data are gathered to compute the calibration; in this part also 200 samples are acquired;
the last part has an indefinite duration when the sensor is moved while real-time data are displayed on the different figures.
Two programs are achieved, depending of the content of the last part. In this case there is a script and only a callback function. The period of data reading is 200 ms.
Mainly it computes:
All the time the last N=200 samples of these measurements are available.
A part of the script is presented in the following.
By running the previous program, the last 200 samples of some of the measurements obtained from the gyroscope and magnetometer are displayed in real-time.
Thus, the two waveforms of the top of Figure 7 are achieved using the gyroscope while the other two from the bottom part are achieved using the magnetometer. In each case the heading is computed. The gyroscope-based angle around z axis or heading is computed using the angular rate around the z axis, see the second waveform. The heading computed by the magnetometer presented in the third waveform is based on its x and y reading which are presented in the last waveform. It can be seen that the two waveforms that represent the heading have the same variation, except at the start. Thus the gyroscope-based heading starts from zero while magnetometer-based heading starts from about 60 degrees because it indicates the north.
Some measurements obtained from gyroscope (the two waveforms at the top) and magnetometer (the two waveforms at the bottom).
By using the movement sensors, 3D orientation of a device can be computed [13, 14, 15, 16, 17]. This can be represented in three ways: quaternion, Direction Cosine Matrix (DCM) and Euler angles. The last representation means the rotational angles around the three axes, called pitch, roll and yaw but has a disadvantage because can reach in a singularity state. DCM does not have a singularity state but needs 3x3 elements. Thus the best representation is quaternion which represents a complex number having four components [13],
where
Using the accelerometer allows only computing pitch and roll angles because a rotation around z axis does not change any of the three outputs. Thus the four elements of the quaternion, denoted
Eq. (9) can be very easily implemented in MATLAB and then the quaternion can be generated by the function
The Euler angles computed by
Both
On the other hand, using the function
The cube that imitates the moving of the CC2650 Sensor Tag, the initial position-left, the position after a 45 degrees rotation around z axis-right.
The Euler angles computed by
First the new elements of the script are presented.
The main MATLAB contributions of this chapter are:
using the new introduced MATLAB functions to access BLE devices and to implement a BLE sensors network
using the table type MATLAB to check if the desired sensors are among the discovered BLE devices
using the structure type MATLAB having a variable number of fields to handle the discovered number of BLE devices
retaining and updating the most recent samples of different measurements corresponding to BLE sensors and display them in real-time
using the quaternions to handle the 3D orientation of an object
using the new introduced MATLAB functions from Sensor Fusion and Tracking Toolbox to determine the parameters that describes 3D orientation
displaying the cube that imitates in real-time the moving of CC2650 Sensor Tag
as a future work, the MATLAB can be used to estimate the position of an object along with 3D orientation; in this way the tracking of an object can be completed.
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Despite rich genetic diversity, manipulation of the cultivars through alternative techniques such as mutation breeding becomes important. Radiation is proven as an effective method as a unique method to increase the genetic variability of the species. Gamma radiation is the most preferred physical mutagen by plant breeders. Several mutant varieties have been successfully introduced into commercial production by this method. Combinational use of in vitro tissue culture and mutation breeding methods makes a significant contribution to improve new crops. Large populations and the target mutations can be easily screened and identified by new methods. Marker assisted selection and advanced techniques such as microarray, next generation sequencing methods to detect a specific mutant in a large population will help to the plant breeders to use ionizing radiation efficiently in breeding programs.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Özge Çelik and Çimen Atak",authors:[{id:"147362",title:"Dr.",name:"Özge",middleName:null,surname:"Çelik",slug:"ozge-celik",fullName:"Özge Çelik"},{id:"147364",title:"Prof.",name:"Çimen",middleName:null,surname:"Atak",slug:"cimen-atak",fullName:"Çimen Atak"}]}],mostDownloadedChaptersLast30Days:[{id:"32842",title:"Sterilization by Gamma Irradiation",slug:"sterilization-by-gamma-irradiation",totalDownloads:74736,totalCrossrefCites:36,totalDimensionsCites:82,abstract:null,book:{id:"1590",slug:"gamma-radiation",title:"Gamma Radiation",fullTitle:"Gamma Radiation"},signatures:"Kátia Aparecida da Silva Aquino",authors:[{id:"102109",title:"Dr.",name:"Katia",middleName:"Aparecida Da S.",surname:"Aquino",slug:"katia-aquino",fullName:"Katia Aquino"}]},{id:"32837",title:"Environmental Gamma-Ray Observation in Deep Sea",slug:"environmental-gamma-ray-observation-in-deep-sea-",totalDownloads:2903,totalCrossrefCites:4,totalDimensionsCites:6,abstract:null,book:{id:"1590",slug:"gamma-radiation",title:"Gamma Radiation",fullTitle:"Gamma Radiation"},signatures:"Hidenori Kumagai, Ryoichi Iwase, Masataka Kinoshita, Hideaki Machiyama, Mutsuo Hattori and Masaharu Okano",authors:[{id:"108174",title:"Dr.",name:"Hidenori",middleName:null,surname:"Kumagai",slug:"hidenori-kumagai",fullName:"Hidenori Kumagai"},{id:"108237",title:"Dr.",name:"Masa",middleName:null,surname:"Kinoshita",slug:"masa-kinoshita",fullName:"Masa Kinoshita"},{id:"137650",title:"Dr.",name:"Ryoichi",middleName:null,surname:"Iwase",slug:"ryoichi-iwase",fullName:"Ryoichi Iwase"},{id:"137656",title:"Dr.",name:"Hideaki",middleName:null,surname:"Machiyama",slug:"hideaki-machiyama",fullName:"Hideaki Machiyama"},{id:"146918",title:"Dr.",name:"Mutsuo",middleName:null,surname:"Hattori",slug:"mutsuo-hattori",fullName:"Mutsuo Hattori"},{id:"146919",title:"Dr.",name:"Masaharu",middleName:null,surname:"Okano",slug:"masaharu-okano",fullName:"Masaharu Okano"}]},{id:"58998",title:"Ionizing Radiation-Induced Polymerization",slug:"ionizing-radiation-induced-polymerization",totalDownloads:1762,totalCrossrefCites:8,totalDimensionsCites:17,abstract:"Ionizing radiation can induce some kinds of reactions, other than polymerization, such as dimerization, oligomerization, curing, and grafting. These reactions occur through a regular radical chain causing growth of polymer by three steps, namely, initiation, propagation, and termination. To understand ionizing radiation-induced polymerization, the water radiolysis must be taken into consideration. This chapter explores the mechanism of water molecules radiolysis paying especial attention to the basic regularities of solvent radicals’ interaction with the polymer molecules for forming the crosslinked polymer. Water radiolysis is the main engine of the polymerization processes, especially the “free-radical polymerization.” The mechanisms of the free-radical polymerization and crosslinking will be discussed in detail later. Since different polymers respond differently to radiation, it is useful to quantify the response, namely in terms of crosslinking and chain scission. A parameter called the G-value is frequently used for this purpose. It represents the chemical yield of crosslinks, scissions and double bonds, etc. For the crosslinked polymer, the crosslinking density increases with increasing the radiation dose, this is reflected by the swelling degree of the polymer while being immersed in a compatible solvent. If crosslinking predominates, the crosslinking density increases and the extent of swelling decreases. If chain scission predominates, the opposite occurs. A further detailed discussion of these aspects is presented throughout this chapter.",book:{id:"6149",slug:"ionizing-radiation-effects-and-applications",title:"Ionizing Radiation Effects and Applications",fullTitle:"Ionizing Radiation Effects and Applications"},signatures:"Mohamed Mohamady Ghobashy",authors:[{id:"212371",title:"Dr.",name:"Mohamed",middleName:null,surname:"Mohamady Ghobashy",slug:"mohamed-mohamady-ghobashy",fullName:"Mohamed Mohamady Ghobashy"}]},{id:"53780",title:"Gamma-Ray Spectrometry and the Investigation of Environmental and Food Samples",slug:"gamma-ray-spectrometry-and-the-investigation-of-environmental-and-food-samples",totalDownloads:2479,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Gamma radiation consists of high‐energy photons and penetrates matter. This is an advantage for the detection of gamma rays, as gamma spectrometry does not need the elimination of the matrix. The disadvantage is the need of shielding to protect against this radiation. Gamma rays are everywhere: in the atmosphere; gamma nuclides are produced by radiation of the sun; in the Earth, the primordial radioactive nuclides thorium and uranium are sources for gamma and other radiation. The technical enrichment and use of radioisotopes led to the unscrupulously use of radioactive material and to the Cold War, with over 900 bomb tests from 1945 to 1990, combined with global fallout over the northern hemisphere. The friendly use of radiation in medicine and for the production of energy at nuclear power plants (NPPs) has caused further expositions with ionising radiation. This chapter describes in a practical manner the instrumentation for the detection of gamma radiation and some results of the use of these techniques in environmental and food investigations.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Markus R. 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Some candidates of the GeV counterpart of gamma-ray bursts, observed by Tupi telescopes, are also presented.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Carlos Navia and Marcel Nogueira de Oliveira",authors:[{id:"189908",title:"Dr.",name:"Carlos",middleName:null,surname:"Navia",slug:"carlos-navia",fullName:"Carlos Navia"},{id:"243084",title:"MSc.",name:"Marcel",middleName:null,surname:"De Oliveira",slug:"marcel-de-oliveira",fullName:"Marcel De Oliveira"}]}],onlineFirstChaptersFilter:{topicId:"1220",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:290,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. 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After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",institutionString:null,institution:{name:"Universidade Paulista",institutionURL:null,country:{name:"Brazil"}}},{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",slug:"juan-jose-valdez-alarcon",fullName:"Juan José Valdez-Alarcón",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBfcQAG/Profile_Picture_1631354558068",institutionString:"Universidad Michoacana de San Nicolás de Hidalgo",institution:{name:"Universidad Michoacana de San Nicolás de Hidalgo",institutionURL:null,country:{name:"Mexico"}}},{id:"161556",title:"Dr.",name:"Maria Dos Anjos",middleName:null,surname:"Pires",slug:"maria-dos-anjos-pires",fullName:"Maria Dos Anjos Pires",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS8q2QAC/Profile_Picture_1633432838418",institutionString:null,institution:{name:"University of Trás-os-Montes and Alto Douro",institutionURL:null,country:{name:"Portugal"}}},{id:"209839",title:"Dr.",name:"Marina",middleName:null,surname:"Spinu",slug:"marina-spinu",fullName:"Marina Spinu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLXpQAO/Profile_Picture_1630044895475",institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"92185",title:"Dr.",name:"Sara",middleName:null,surname:"Savic",slug:"sara-savic",fullName:"Sara Savic",profilePictureURL:"https://mts.intechopen.com/storage/users/92185/images/system/92185.jfif",institutionString:'Scientific Veterinary Institute "Novi Sad"',institution:{name:'Scientific Veterinary Institute "Novi Sad"',institutionURL:null,country:{name:"Serbia"}}}]},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. 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He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. 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He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. 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:"27",type:"subseries",title:"Multi-Agent Systems",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. 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The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence"},{id:"23",title:"Computational Neuroscience",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. This topic is dedicated to biologically plausible descriptions and computational models - at various abstraction levels - of neurons and neural systems. This includes, but is not limited to: single-neuron modeling, sensory processing, motor control, memory, and synaptic plasticity, attention, identification, categorization, discrimination, learning, development, axonal patterning, guidance, neural architecture, behaviors, and dynamics of networks, cognition and the neuroscientific basis of consciousness. Particularly interesting are models of various types of more compound functions and abilities, various and more general fundamental principles (e.g., regarding architecture, organization, learning, development, etc.) found at various spatial and temporal levels.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness"},{id:"24",title:"Computer Vision",scope:"The scope of this topic is to disseminate the recent advances in the rapidly growing field of computer vision from both the theoretical and practical points of view. Novel computational algorithms for image analysis, scene understanding, biometrics, deep learning and their software or hardware implementations for natural and medical images, robotics, VR/AR, applications are some research directions relevant to this topic.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR"},{id:"25",title:"Evolutionary Computation",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization"},{id:"26",title:"Machine Learning and Data Mining",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence"},{id:"27",title:"Multi-Agent Systems",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",annualVolume:11966,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},{id:"39",title:"Environmental Resilience and Management",keywords:"Anthropic effects, Overexploitation, Biodiversity loss, Degradation, Inadequate Management, SDGs adequate practices",scope:"\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"