The types of couplers/splitter, the advantages and the disadvantages.
\r\n\tOver the years, the concept of maintenance became more comprehensive, reducing fault occurrence and increasing industrial system availability. Besides, reliability, safety, and criticality requirements were associated with the system or equipment under analysis. Maintenance strategies or schemes can be classified as corrective (run-to-break), preventive (time-based), and predictive (condition-based maintenance). Corrective maintenance is only performed after an occurrence of a fault. Therefore, it involves unexpected breakdowns, high costs, changes in the production chain, and it could lead to catastrophic events. Preventive maintenance and interventions occur based on a scheduled maintenance plan or the equipment's mean time between failures. Although it is more effective than corrective maintenance, unexpected failure may still occur by preventing most failures. Additionally, the process cost is still high, especially the costs associated with labor, inventory, and unnecessary replacement of equipment or components.
\r\n\tOn the other hand, predictive maintenance analyses the equipment condition so that a possible fault can still be identified at an early stage. Predictive maintenance aims to identify a machine anomaly so that it does not result in a fault. Such maintenance involves advanced monitoring, processing, and signal analysis techniques, which are generally performed non-invasively and, in many cases, in real-time. In the case of machines or processes, these techniques can be developed based on vibration, temperature, acoustic emission, or electrical current signal monitoring. It should be noted that monitoring such signals or parameters to verify the operating condition is called condition monitoring. Condition monitoring aims to observe the machine's current operational condition and predict its future condition, keeping it under a systematic analysis during its remaining life. In this sense, a fault condition can be detected and identified from systematic machine condition monitoring. A diagnosis procedure can be established, whereby properly investigating the fault symptoms and prognosis.
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\r\n\tThis book will aim to merge all these ideas in a single volume, aggregate new maintenance experiences, apply new techniques and approaches, and report field experiences to establish new maintenance processes and management paradigms.
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In order to have a therapy, it is known that we must first have a correct diagnosis. In this respect, we present an evolved oncology diagnostic system (http://www.carismolecularintelligence.com/i-o/). First of all, immunotherapy options should be sought through the development of complex immunoregulatory pathways. One of the systems that can be used in immunological diagnosis is Caris Molecular Intelligence. This system provides oncologists with reliable molecular information to make decisions about the use of immunotherapy. The tests are validated for testing PD-L1, MSI, and tumor mutation load (TML). Programmable cell death-ligand 1 (PD-L1) is one of the most important control immune proteins that mediates tumor-induced suppression by T-cell downregulation. Expression of PD-L1 may indicate a more likely response to immunotherapy. Of course, a perfect marker to predict the response to PD-L1 inhibitor therapy has not been validated for the moment, but with these tests, we have an important orientation (Cochrane Collaboration Guidelines).
Microsatellite instability (MSI) is caused by the failure of the mismatch repair (MMR) system. MSI-High correlates with the increase in neoantigenic burden, which is more likely to respond favorably to immunotherapy.
Tumor mutation load (TML) measures the total number of non-sinusoidal somatic mutations identified on the megabase of the genome coding region. High TML supports neoantigens and responds favorably to immunotherapy.
The immune system is capable of recognizing and destroying tumor cells as well as pathogens. However, one of the hallmarks of cancer is its ability to avoid the immune system [1].
There are a lot of complex interactions between the cells presenting the antigen, the lymphocytes, and the tumor cells. The most studied is the cell membrane T-cell receptor binding, called programmed cell death 1 (PD-1), and its ligands 1 or 2 (PD-L1 or PD-L2) expressed by some tumor cells. This interaction results in inactivation of T lymphocytes in an effort to avoid the immune response against tumor cells [2, 3]. Inhibition of this pathway is the target of inhibitors of immune control points. There are two types of agents: anti-PD-1 and anti-PD-L1 monoclonal antibodies.
Among these, anti-PD-1 agents that bind the lymphocyte receptor and block both PD-L1 and PD-L2 bindings are considered to be more toxic than anti-PD-L1 due to their broad spectrum of clinical activity. However, this has not been confirmed by recent clinical trials [4, 5]. Pembrolizumab and nivolumab, two monoclonal antibodies against PD-1, as well as avelumab monoclonal IgG1 anti-PD-L1 antibodies, atezolizumab and MEDI4736, showed consistent antitumor activity against NSCLC [6].
Despite an improvement in overall survival (OS) by platinum-based chemotherapy (NSCLC Meta-analyses Collaborative Group, 2008), prognosis remains unsatisfactory for patients with advanced NSCLC, with a median survival of 8–12 months [7, 8].
In 2006, there was a plateau for chemotherapy in a study that none of the four chemotherapy regimens compared offered a significant advantage over the others in the treatment of advanced non-small cell lung cancer [8].
The development in molecular characterization of NSCLC, especially in histological subtypes of adenocarcinoma, has allowed the identification of key genetic aberrations in NSCLC, which can be addressed with molecular targeted therapy. Genetic aberrations in EGFR, ALK, ROS1, RET, BRAF, and NTRK have a predictive value for susceptibility to receptor tyrosine kinase inhibitors [9, 10, 11]. Despite the success of molecular diagnostics, acquired resistance and disease progression are inevitable [9, 10, 11].
Treatment options for patients with small-cell lung cancer (SCLC) where the disease progressed after platinum-based chemotherapy are even more limited.
Immunotherapy in cancer has been described as any therapy that interacts with immunity. Immunotherapy in cancer can be classified into passive and active types. Passive immunotherapy has been described as administration of an active agent produced or generated outside the patient’s body. Theoretically, such an approach does not depend on the host’s own immune system to have an effect. Examples of passive immunotherapy include the use of monoclonal antibodies, such as trastuzumab [12, 13], and adoptive cell therapy, such as tumor-infiltrating lymphocytes (CAR-T cell) [14]. This new approach of therapy has and specific toxicity: cytokine release syndrome, neurologic toxicity, “on target/off tumor” recognition, and anaphylax [15].
Active immunotherapy involves stimulating or determining the host’s immune system to recognize a tumor as a foreign. Examples of active immunotherapy include vaccination against cancer with tumor antigens and an adjuvant enhancement of immune cell function with cytokines, as well as targeting of immune control regulators with immune control inhibitor control.
Inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) are used in NSCLC and SCLC.
Studies that examine the efficacy of cytokines such as interferon alpha and interleukin-2 (IL-2) in lung cancer patients were negative and will not be discussed [16].
Therapeutically acting vaccines in cancer are designed to eliminate cancer cells by increasing their own immune responses. This type of vaccine contrasts with prophylactic vaccines, which are usually administered to healthy people. Cancer vaccines can be classified into several major types, such as cellular vaccines, peptide vaccines, and genetic vaccines [17].
Vaccines against cancer, despite despite setbacks attempt to harness the patient’s immune system to fight tumor cells and show a promise in clinical trials.
Cellular vaccines may be either autologous or allogeneic. Autologous tumor cell vaccines are developed by isolating tumor cells from an individual (patient), creating a vaccine that is administered back to the same patient, usually in combination with an adjuvant that stimulates the immune system. These vaccines have been among the first types of cancer vaccines tested and have the advantage of provoking an immune response to a wide range of tumors. Antigens expressed by the patient’s own tumor result in tumor destruction. Although similar to autologous vaccines, allogeneic vaccines are obtained by administering tumor cells to a patient, creating a vaccine that is then administered to another patient with the same type of cancer [18].
Unlike cellular vaccines that are made directly from patient tumors, peptide vaccines are often synthesized in vitro to mimic tumor-associated proteins in order to elicit an immune response against tumor cells expressing that protein [19].
Genetic vaccines are composed of DNA molecules or synthetic RNAs encoding tumor-associated proteins and are administered either alone or packaged in a nonpathogenic virus. The genetic material is taken up by the recipient cells, translated into proteins encoded, processed, and presented to the immune system to elicit the immune response against tumor-associated proteins [20].
DNA vaccination has suddenly become a favored strategy for inducing immunity. The molecular precision offered by gene-based vaccines, together with the facility to include additional genes to direct and amplify immunity, has always been attractive. However, the apparent failure to translate operational success in preclinical models to the clinic, for reasons that are now rather obvious, reduced initial enthusiasm. Recently, novel delivery systems, especially electroporation, have overcome this translational block. Here, we assess the development, current performance, and potential of DNA vaccines for the treatment of cancer.
Early studies on Calmette-Guerin adjuvant Calmette-Guerin adjuvant and neoadjuvant bacillus vaccine therapy were negative [21, 22].
In the modern age, multiple-stage, locally advanced, and advanced NSCLC vaccine studies have been conducted. The recombinant protein-associated anti-melanoma-antigen-associated antigen (MAGE)-A3 vaccine has been extensively studied in adjuvant therapy after complete resection. A randomized phase II trial showed that for patients with stage IB–II, MAGE-A3 in NSCLC, who did not receive any adjuvant chemotherapy, there was a tendency toward survival gain. And, survival without signs of disease was positively influenced by the MAGE-A3 vaccine compared to placebo after a median follow-up to 70 months (HR, 0.75; 95% CI, 0.46–1.23; p = 0.254) [23].
However, clinical benefit was not found in the randomized, double-blind, placebo-controlled phase III (MAGRIT) study in fully resected NSCLC IB–IIIA MAGE-A3, with or without adjuvant chemotherapy. Subsequently, for the total population in this study, median disease-free survival was 60.5 months for the MAGE-A3 vaccine group and 57.9 months for the placebo group (HR, 1.02; 95% CI, 0.89–1.18; p = 0.74). In the subgroup that performed adjuvant chemotherapy, median disease-free survival was 58.0 months in the vaccine group and 56.9 months in the placebo group (HR, 0.97; 95% CI, 0.80–1.18; p = 0.76) [24].
Tecemotide (L-BLP25) is a peptide vaccine based on a 25 amino acid sequence of mucin-1 (MUC1), which has shown promising activity in locally advanced NSCLC in a phase II study [25].
Subsequently, the result led to the initiation of two randomized trials. One was a complete phase III trial, START, in which the placebo tecemotide was compared for patients with stage III NSCLC without disease progression after chemoradiation therapy [26].
The second study, INSPIRE, was a randomized phase II study of Asian patients that did not have convincing results after the Asian phase [27].
Analysis of the START study showed that there was no significant difference in median overall survival between the tecemotide arm and placebo arms (25.6 months vs. 22.3 months; HR adjusted, 0.88; 95% CI, 0.75–1.03; p = 0.123). However, following a prespecified subgroup analysis, median overall survival was different between the vaccine arm and the placebo arm for patients receiving concomitant chemoradiation therapy (30.8 months vs. 20.6 months; HR, 0.78; 95% CI, 0.64–0.95; p = 0.016) compared with patients receiving sequential chemoradiation therapy (19.4 months vs. 24.6 months; HR, 1.12; 95% CI, 0.87–1.44; p = 0.38) [28].
In the advanced stage of the disease, the TG4010, another vaccine targeting MUC1, used a viral vector to express both MUC1 and IL-2 (a T-cell stimulus). The results were promising.
In a phase IIb study (TIME) results (part of the randomized, double-blind, placebo-controlled, phase IIb/III study), showed that in the overall population, disease-free survival was 5.9 months for the TG4010 group and 5.1 months for placebo (HR, 0.74; 95% CI, 0.55–0.98; p = 0.019) [29].
Belagenpumatucel-L is an allogeneic tumor cell tumor vaccine derived from four cell lines of NSCLC with different histologies, also express an antisense transgene for transforming beta2 growth factor that reduces the regulation of its immunosuppressive transformation. The results of a phase II study suggested clinical efficacy in patients with advanced NSCLC, and a randomized phase III (STOP) study was initiated. Patients with stage III/IV NSCLC in whom the disease did not progress after platinum-based chemotherapy received either belagenpumatucel-L or placebo [30]. There was no significant difference in overall survival between the two arms (20.3 months vs. 17.8 months; HR, 0.94; p = 0.594); there was also no difference in progression-free survival (PFS) (4.3 months vs. 4.0 months; HR, 0.99; p = 0.947) [30].
The epidermal growth factor receptor (EGFR) is an important signaling pathway in NSCLC, and a vaccine has been developed against its related EGF ligand, using recombinant human EGF coupled to a carrier protein. In a randomized phase II trial, patients with stage IIIB/IV NSCLC were randomly assigned to receive the best supportive treatment or EGF vaccines after first-line chemotherapy [31]. In the global population, there was a trend toward improved overall survival and a significant survival advantage for patients who had a good antibody response to the EGF [31].
A subsequent phase III study included patients with stage IIIB/IV NSCLC who were randomly assigned to the first line of chemotherapy to make the vaccine or the best supportive care. In the safety population, overall survival was 10.83 months for the vaccine arm and 8.86 months for the control arm [32]. For patients who received at least four doses of vaccine, overall survival differed significantly between the vaccine group and the supportive treatment group (12.43 months vs. 9.43 months; HR, 0.77; p = 0.036). In addition, overall survival was longer (14.66 months) for patients vaccinated with high concentrations of EGF at the baseline [32].
Ipilimumab in combination with chemotherapy has been studied in patients with advanced NSCLC who have not received the previous treatment. In this phase II triple-arm study, patients were randomly assigned to chemotherapy (carboplatin plus paclitaxel), sequential chemotherapy with ipilimumab, or chemotherapy with concomitant ipilimumab. The primary endpoint of the study was overall survival and progression-free survival, which was 4.6 months for the chemotherapy arm, 5.7 months for the sequential ipilimumab chemo arm (HR, 0.72; p = 0.05), and 5.5 months for the ipilimumab arm concomitantly with chemotherapy (HR, 0.81; p = 0.13) [33]. Progression-free survival was better in NSCLC patients with squamous histology than patients with nonsquamous NSCLC. To confirm these results, a larger phase III trial (NCT02279732) was initiated for patients with squamous cell NSCLC.
Conclusion of the study was that phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS, which supports additional investigation of ipilimumab in NSCLC [33].
In the Govindan study ipilimumab added to chemotherapy (carboplatin plus paclitaxel) did not improve the survival of patients with advanced NSCLC [34].
PD-1 inhibitors include agents such as nivolumab and pembrolizumab. Nivolumab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that disrupts PD-1-mediated signaling, thus releasing T cells from their inhibitory interaction with PD-L1 and PD-L2. Pembrolizumab is a monoclonal antibody, the humanized IgG4/kappa isotype, which also blocks the binding of PD-L1 and PD-L2 to PD-1 on T cells, resulting in activation of tumor-specific cytotoxic T cells. Cytotoxicity is complement-dependent (CDC) (Alsaab) [35].
Action may be important because cytotoxicity can cause an exhaustion of activated T cells and infiltrating lymphocytes into tumors. PD-1 is expressed on effector T cells and other immune cells [36].
Checkmate 026 did not show a benefit in PFS for nivolumab versus chemotherapy. The authors reveal the fact that nivolumab monotherapy did not result in longer progression-free survival than platinum-based chemotherapy as first-line treatment for stage IV or recurrent NSCLC in a broad population of patients with a PD-L1 expression level of 5% or more. Overall survival with single-agent nivolumab was similar to overall survival with platinum-doublet chemotherapy. Nivolumab had a favorable safety profile as compared with chemotherapy, and no new safety signals were observed [37].
The new data from the phase 1b CA209-003 study were presented at the American Association for Cancer Research annual meeting: “The longest follow-up to date on patients treated with nivolumab for advanced non-small cell lung cancer (NSCLC) shows a 16% 5-year overall survival (OS) rate, according to new results presented here at the American Association for Cancer Research annual meeting.” Suzanne Topalian, from Johns Hopkins University, and a coinvestigator (April 03, 2017): “the 5-year overall survival really quadrupled the survival that we would otherwise expect if these same patients had received chemotherapy” (April 03, 2017) (https://www.medscape.com/viewarticle/878148).
Nivolumab provides a long-term clinical benefit and a favorable tolerability profile compared to docetaxel in previously treated patients with advanced NSCLC [38]. FDA approved of nivolumab for second-line treatment of patients with advanced NSCLC.
In a single-arm phase II study (CheckMate 063) with nivolumab for patients with squamous cell NSCLC who were treated with third-line therapy and beyond, the partial response rate was 14.5, and 26% of patients had a stable disease [4]. Overall survival was 8.2 months, and 1-year survival was about 41%. Noteworthy, the study population was very refractory to treatment, with 65% of patients treated with at least three previous systemic therapy lines. In addition, 61% of patients had disease progression as the best response to the latest therapy [39].
In another phase II trial (CheckMate 153), 824 patients with advanced NSCLC were treated for 1 year with nivolumab. The partial response and stable disease rates were 12 and 44%, respectively. The answers were independent of the PD-L1 expression [40].
The second-line treatment with nivolumab was superior to docetaxel in two subsequent phase III randomized phases in advanced NSCLC patients receiving double-blind platinum chemotherapy.
In a study of 272 patients with squamous NSCLC (CheckMate 017), median overall survival and 1-year survival were better for nivolumab than for docetaxel. The risk for death was 0.59 with nivolumab (p < 0.001) [6].
In the study (CheckMate 057), which included patients with advanced nonsquamous NSCLC histology, nivolumab in line 2 was also associated with better overall survival and survival over 1 year, also better than docetaxel (HR, 0.73) [41]. In subset analysis of subset biomarker values, PD-L1 expression ≥1, ≥5, and ≥10% corresponded to an improvement in PFS with a HR of 0.70, 0.54, and 0.52, respectively, and in OS with a HR of 0.58, 0.43, and 0.40. In contrast, in tumors with a low PD <1, <5, and <10% PD-L1 expression, HR for PFS was 1.19, 1.31, and 1.24, respectively, and for OS was 0.87, 0.96, and 0.96 [41].
The safety and efficacy of single-agent nivolumab in first-line treatment of patients with advanced NSCLC have been reported in CheckMate 012 adverse events occurred in 71% of patients, the most common being fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). The overall confirmed response was 23%, and progression-free survival and overall survival were 3.6 months and 19.4 months. The nonprogression-free survival rate of 24 weeks was 41%. The survival rate at 1 year was 73% [42].
Recently, in a phase III study, first-line nivolumab compared to a platinum-based chemotherapy for tumors with a PD-L1 expression of 5% or greater (CheckMate 026) showed progression-free survival greater for the chemotherapy arm, but overall survival was better for the nivolumab arm [43]. The objective response rate was lower for the nivolumab arm. In conclusion, nivolumab monotherapy did not result in longer progression-free survival than platinum-based chemotherapy as first-line treatment for stage IV or recurrent NSCLC. In this study the PD-L1 expression level was 5% or more [43].
SCLC is most often an extended stage disease at the time of diagnosis. Although the first line of platinum-based chemotherapy has activity, the disease progresses inevitably, and response rates in the second-line treatment are low and are not sustainable. The activity and safety of nivolumab with or without ipilimumab in previously treated SCLCs were evaluated in CheckMate 032. The objective response rate was 10% with nivolumab 3 mg/kg alone, 23% with 1 mg/kg of nivolumab in combination with 3 mg/kg of ipilimumab, and 19% with 3 mg/kg of nivolumab in combination with 1 mg/kg of ipilimumab. PD-L1 expression was not associated with responses [44].
Patients with small-cell lung cancer (SCLC) and a high tumor mutation burden had an important increase in survival (near doubling in response rate and 1-year overall survival) with ipilimumab combined with nivolumab versus nivolumab alone.
The efficacy and safety of pembrolizumab at two different doses in previously untreated patients, advanced NSCLC, were reported in the Keynote-001 study. The objective response rate was 19.4%, and the median response time was 12.5 months. The progression-free survival was 3.7 months, and overall survival was 12.0 months [45]. The objective response rate was 18% in those treated previously and 24.8% of untreated patients. The objective response rate was 45.2%, and no time to progression was 6.3 months. The objective response rate was similar regardless of dose, schedule, and histology subtype. The response rate was higher among smokers than nonsmokers. Treatment-related adverse events of any grade occurred in 70.9% of patients, 9.5% having a grade 3 or higher adverse event [45].
Pembrolizumab was evaluated in a phase II/III study of patients previously treated with advanced NSCLC (Keynote-010). A total of 1034 patients were randomized to receive either 2 mg/kg dose or 10 mg/kg of pembrolizumab or 75 mg/m2 of docetaxel every 3 weeks [46]. All patients had at least 1% tumor cells that were positive for PD-L1. Overall survival was improved with both doses of pembrolizumab compared to docetaxel. Among patients with at least 50% of the tumor cells expressing PD-L1, overall survival rates were 14.9 and 17.3 months with pembrolizumab at doses of 2 mg/kg and 10 mg/kg, respectively, compared to 8.2 months with docetaxel. Any degree of treatment-related adverse events occurred in 63% of pembrolizumab 2 mg/kg and 66% of patients receiving 10 mg/kg. The treatment-related toxicity was higher (81%) in the docetaxel arm.
Grade 3–5 treatment-related adverse events were less common in pembrolizumab-treated patients (2 mg/kg (13%), 10 mg/kg (16%)) versus docetaxel (35%) [46].
The Keynote-024 phase 3 clinical trial was the basis for pembrolizumab approval as a first-line treatment for patients with a diagnosis of metastatic NSCLC for whom PD-L1 expression is in 50% or more of tumor cells. Keynote-024 is a randomized, open-label phase 3 study evaluating pembrolizumab monotherapy at a fixed dose of 200 mg compared to the platinum-based chemotherapy standard for the treatment of patients with metastatic NSCLC with both squamous and unscrupulous histologies.
In phase III trial for first-line therapy of patients with advanced NSCLC (Keynote-024), with a PD-L1 tumor expression of 50% or greater, patients were randomly assigned to pembrolizumab- or platinum-based chemotherapy doublets, and progression-free survival was significantly better for pembrolizumab (HR, 0.50, 95% CI, 0.37–0.68; p < 0.001) median 10.4 months [47].
Overall survival was 0.60 (95% CI, 0.41–0.89; p = 0.005). The estimated percentage of patients in life at 12 months with pembrolizumab was 70%. In addition, the response rate was higher for pembrolizumab than for chemotherapy. Adverse events associated with pembrolizumab therapy were fewer than chemotherapy. The results are innovative because this is the first to demonstrate the superiority of anti-PD-1 therapy to platinum [47].
Preliminary data from a multicohort phase Ib study on pembrolizumab with previously treated PD-L1-positive subjects include a 25% objective response rate and a 31% disease control rate [48].
PD-L1 inhibitors also inhibit PD-1/PD-L1 interactions. PD-L1 inhibitors include atezolizumab, durvalumab, and avelumab. Atezolizumab and durvalumab are human IgG1 anti-PD-L1 antibodies with mutations in their Fc domains to eliminate both antibody-dependent cell-mediated cytotoxicity (ADCC) activity and complement-dependent cytotoxicity (CDC) activity. Avelumab is a fully human IgG1 anti-PD-L1 monoclonal antibody and, unlike another PD-1/PD-L1 inhibitor, has been shown to retain ADCC and CDC activity in preclinical studies [49].
In a single-arm phase II study (IMpower 110 study), the objective response rate for atezolizumab was 16%, regardless of PD-L1 expression in immune cells, and 28% in patients with 5% or more high expression PD-L1 [50]. Atezolizumab (MDPL3280A) clearly is an added value in the treatment of advanced-stage pretreated NSCLC. Its interest in contrast with other immune checkpoint inhibitors relies on its efficacy, even in low or no PD-L1 expression subgroups. Considering that the efficacy of anti-PD-1 such as pembrolizumab or nivolumab is overall higher in PD-L1-positive patients, atezolizumab might be preferable in PD-L1-negative patients. It will be necessary to consider other variant methods of PD-L1 testing used for each therapy to further explore this hypothesis [51].
In a randomized phase II (Poplar) study in patients receiving platinum-based chemotherapy, atezolizumab was associated with a higher overall survival (HR, 0.73; CI 95%, 0.53–0.99; p = 0.04) [52]. In another phase II trial (BIRCH), advanced NSCLC patients who were selected for PD-L1 expression received atezolizumab as first-line or as a subsequent therapy. Response rates ranged from 17 to 27% [53], and median overall survival was 14 months for patients receiving atezolizumab as the first line of therapy. Overall survival has not yet been achieved for patients receiving atezolizumab as a subsequent therapy [53]. In the OAK study, a phase III trial of previously treated NSCLC patients randomly assigned to atezolizumab or docetaxel, the overall survival was significantly better for atezolizumab (13.8 months vs. 9.6 months; HR, 0.73; 95% CI, 0.62–0.87; p = 0.0003) [54]. The OAK study led to the FDA approval of atezolizumab for second-line therapy of advanced NSCLC [54].
In a phase I/II study with durvalumab in 2009 in the first-line treatment in NSCLC patients irrespective of PD-L1 status, the overall response rate was 27 and 29% for PD-L1-positive tumors (defined as ≥25% of tumor cells expressing PD-L1) and 11% in PD-L1-negative tumors [55]. In a phase II trial of patients with advanced NSCLC who received at least two previous systemic therapy lines, the activity was extremely encouraging. The objective response rate and survival rate at 1 year increased according to the PD-L1 expression: 7.5% (PD-L1 expression less than 25%), 16.4% (more than 25% expression), and 30.9% (greater than 90% expression). The corresponding 1-year survival rates were 34.5, 47.7, and 50.8% [56].
The study PACIFIC was presented to the ESMO Congress 2017 and was a randomized, double-blind, international, phase 3 study comparing durvalumab as consolidation therapy with placebo in patients with stage III, locally advanced, unresectable NSCLC that had not progressed after platinum-based chemoradiotherapy. Median progression-free survival as assessed by means of blinded independent central review was 16.8 months (95% confidence interval [CI], 13.0–18.1) with durvalumab versus 5.6 months (95% CI, 4.6–7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42–0.65; two-sided p < 0.001). Authors consider that this study will change the clinical practice [57].
CTLA-4 and PD-1/PD-L1 are combination. CTLA-4 inhibitors are also studied in conjunction with PD-1 and PD-L1 inhibitors. Results of preclinical studies indicate that this combination can work synergistically to produce improved antitumor activity [58].
Nivolumab was combined with ipilimumab for first-stage NSCLC in setting up in a phase I (CheckMate 12) study. The results included objective response rates ranging from 13 to 39%.
In NSCLC, the first-line nivolumab plus ipilimumab had a tolerable safety profile and showed an encouraging clinical activity characterized by a high response rate and durable response. In our study, the results of this study are the first suggestion of improved benefit compared with anti-PD-1 monotherapy in patients with NSCLC, supporting further evaluation of this combination in a phase 3 study [59].
Durvalumab was combined with the tremelimumab CTLA-4 inhibitor in a phase Ib study of patients with advanced NSCLC. Although many adverse events occurred during the study dose phase, the antitumor activity (23% objective response rate) was evident regardless of the PD-L1 status in the evaluable patients in the dose study—the expansion phase of the study [60].
In a phase III randomized study, the frontline durvalumab, either in combination with tremelimumab or as a single agent, did not improve progression-free survival (PFS) in patients with stage IV metastatic non-small cell lung cancer (NSCLC) compared with standard platinum-based chemotherapy [61].
Immunotherapy has become one of the most important therapeutic tools in advanced lung cancer. Existing studies have revealed a response rate of between 13 and 39%. It is also important that this therapy, unlike TKI-targeted therapy, also responds to smokers who make up most of the lung cancer patients.
Another important benefit from immunotherapy in advanced lung cancer is that squamous non-small cell lung cancer also responds to this therapy. Some promising results are and in treatment of small-cell lung cancer.
From existing studies, it is trembling that immunotherapy can improve survival compared to chemotherapy in a selected patient population, both in the first line and in the second line.
There is not yet a valid predictive marker that can be used to choose patients who will respond to immunotherapy. Currently, the only marker used is PD-1 expression that does not have a good validity. For the moment, there are not criteria to select patients for treatment with PD-1 or PD-L1 inhibitor because data to compare these two pathways is lacking. Better results were however obtained with a percent of PD-L1more then 50%. More study are needed to define the best combination of immunotherapy with chemotherapy or radiotherapy.
Vaccine therapy is promising but needs additional evaluation. Vaccine in combination with other therapeutic modalities especially checkpoint inhibitors is possible to have some benefits and must be studied.
Many guidelines are developed to treat side effects of immunotherapy. Despite a correct supportive therapy, some side effects are life-threatening. But generally, the quality of life of patients treated with immunotherapy is improved.
This work is conducted to develop an optical fiber passive device based on polymer optical fiber, specifically a splitter or also can be known as a coupler. This device is developed as an effective green-technology based device yet providing an economic solution for home-networking fiber to the home system. The splitter is mainly developed for short-haul communication system where the splitter is developed using polymer optical fiber that has been tapered using harmless organic compound chemical solvent which is acetone. Other method of tapering used in this research is by using side polish where only one side of the diameter of the fiber strands is being tapered. The platform of the device is built using acrylic material having customization of dimensions of the prototype design. Geometrical shapes of circular blocks and ellipse blocks were developed with various bending radii where the tapered fibers are attached to the groove of the blocks and brought closed together. Parameters that involve in this research includes bending radius,
The coupler/splitter developed in this research includes the preparation of the fibers by etching, side polishing, and building the splitter platform which includes the geometrical blocks with various radii of the macro-bending. The purpose of etching is to eliminate the cladding layers in order to allow the propagation of the modes to travel into the other fibers. However, other factor that could help the transfer of modes from one fiber to the other is macro-bending of the fiber. Evanescent field allows the modes in the fiber to propagate in the cladding. When the fiber bends, losses happen due to the evanescent field that would have to travel faster in order to keep up with the core field. At certain bending, i.e., beyond critical bending, the modes tend to radiate away. In consequence of tapering the multimode optical fiber cladding, higher modes of the fiber are removed while some modes are redistributed.
\nOther contributing factors that encourage the transfer is the force exertion unto the blocks and fibers attached to the blocks. Some pressure is exerted upon the fibers in order to eliminate any macro-gap that exists between the two parallel fibers. Therefore, when the two fibers are lapped together, the transfer of modes between the two fibers can prevent any leaks of modes that radiates away due to the evanescent field when bending. Length of the parallel coupling also contributes to the effectiveness of mode coupling since when the coupling length is short, only small number of modes get transferred. Coupling length is varied with several bending radii and diameter of the cores to find the optimum performance parameters based on the characterization.
\nIn applying analytical modelling method to characterize and analyze the device, two important theories are used, that are Coupled Mode Theory and Hertz’s Law. A simplified couple mode theory between two parallel, lapping multimode step-index fibers are studied where parameters in control which is radius of contact area or coupling length are induced or related by the amount of force or pressure exerted upon the lapping fibers that are attached to geometrical blocks with various radii. The radiation of the propagation modes is induced by the bending of the fiber accordingly to the radius of the geometrical blocks. Depending on the coupling length of the parallel fibers lapped together, the power transfer between them varies in accordance to the length. However, due to physically lapping fibers without any fusion between them, force or pressure is an important aspect in this study so that to eliminate or at least reduce the number of losses of the power transfer due to macro gap. Two important theories are applied which are Hertz’s Law and Couple Mode Theory that relates to analytical study of force exertion and radius of contact area.
\nPolymer optical fibers (POF) show great advantage compared to glass fibers in short-haul communications links due to its flexibility and less expensive, although they are not used for very long distances because of their relatively high attenuation. These characteristics are an advantage for fiber-to-the-home networking having high speed communication. An example would be Internet access within home or within an office [1].
\nThere are several methods that can be used to develop optical fiber coupler/splitter. However, this work aimed to develop optical splitter/coupler that is green-based, safe to use, low cost, economic, easy to install and has multiple solutions for important performance parameters required by users. The optical fiber pairs and the combination of blocks allow the designed platform to produce several performance parameters with minimum loss. Therefore, the device developed can also be a do-it-yourself device since it is customer friendly. The technique used in the process of development is harmless and requires detailed measurement, thus, producing an effective yet low cost POF splitter/coupler that can be used widely by the users.
\nCommercially available POF for data communications are polymethilmethacrylate (PMMA) POF core material as shown in Figure 1. For visible light of 650 nm, the IR-absorption is 95.9 dB/km, the Rayleigh scattering is 10.3 dB/km and total loss of 106.2 dB/km with no UV-absorption [2]. PMMA POF used in this study is manufactured by Mitsubishi Rayon (Japan). PMMA is produced from ethylene, hydrocyanic acid, and methyl alcohol. It is resistant to water, lyes, diluted acids, petrol, mineral oil and turpentine oil. PMMA tensile strength is approximately 8 kN/cm2. The refractive index of the core is 1.492 and the cladding is 1.402. The transition temperature lies between +95\n
PMMA polymer optical fiber with diameter 1 mm.
Polymer optical fiber was introduced in 1960s after glass optical fiber was introduced shortly as a transmission medium for optical communications. Over the years, the transmission capability of POF is improved from having a large attenuation as large as 300 dB/km to 20 dB/km at 650 nm wavelength [3]. POF technology has advantage characteristics such as low insertion loss, low-cost production, thermal stability, mechanical stability, and mass production reliability [3]. Although POFs have higher loss than silica fibers or glass fibers, POFs are never used in long distance communication systems but are being used in intra office communication systems where one requires only a few hundred meters of the fiber. POFs are providing low-cost solutions to short distance applications such as local area networks (LAN), high speed internet access and in vehicles [4].
\nPOF offer the advantages of being lightweight, flexible and easy to handle. Other advantage includes having large fiber cross-section which makes it easier to positioned fiber end at the transmitter or receiver compared to GOF that needs an expensive precision component to center the fiber. PMMA POF has 1 mm diameter which makes it easy to handle and flexible compared to GOF where the fiber is quite easy to break. PMMA POF is also easy to cut, grind, polish or melt. It also has high flex resistance where the cost used is low even under intense loading conditions that encountered in mechanical engineering applications. Other than that, the easy connecterization of the end faces can be performed cost effectively even after assembling in the field [5].
\nIn respect of electromagnetic compatibility, electrical isolation, immunity to eavesdropping and risk of explosion in hazardous areas, polymer optical fiber and glass fiber have the advantages compared to copper since the photons as the carrier of information in optical fiber have no electrical charge like the electrons which carry the information in copper conductors. In terms of external and mechanical properties, small bending radius and high flexibility are advantages that make POF an attractive choice compared to GOF. The low weight of optical fibers compared with copper is an advantage in most applications.
\nCouplers work by combining two or more optical signals and combined them into one signal being modulated and propagates through one single fiber whilst splitter in the other hand, separates the signals at the end of the fiber and send the particular signals to their particular destinations [6].
\nThere are three kinds of optical couplers which are directional, distributive, and wavelength-dependent couplers. The mechanism involves in these couplers can be categorized as diffusion type, area-splitting type, and beam-splitting type. Diffusion couplers involve either evanescent wave coupling or radiative coupling. Two fibers are place in proximity [7] and the length of the parallel lapping cores are measured which is known as coupling length. Once they the gap is reduced, radiation of light or known as evanescent wave coupling will initiate thus power transfer will happen. In radiative coupling, bent fibers are coupled to each other by the radiated field. These works well with multimode fibers. Such example is twisted-pair coupler of fused biconical taper coupler. In the fused section, the fiber cores are still separated from each other but the core modes are converted to cladding modes, therefore, partly coupling optical power from one fiber to the other [8]. Example of distributive couplers would be star coupler and example of beam splitter couplers are monitors coupler. This work mainly focuses on directional coupler that has mechanism of diffusion type. Mode selection in multimode fibers has been done by employing offset-launch techniques and mode scramblers by bending the fiber to leak the high order modes and utilized them [9].
\nLapping technique is chosen due to the simplicity of the design. Since the development focus on customized and low-cost device, lapping technique could easily be implemented. Other technique such as fused coupler has widely been used and the technique is hardly modified for new approach and new research contributions. Butt coupling and core-facet coupling technique in the other hand has alignment problems and to obtain optimum output will require high-end tools. Y-coupling in the other hand could only produce one output only although the performance is excellent. Other techniques are also discussed in Table 1 [3, 5].
\nType | \nTechnique of fabrication | \nAdvantages | \nDisadvantages | \nLoss | \n
---|---|---|---|---|
Y-coupler | \nThe output fibers are ground where end faces completely cover each other | \nHas excellent performance as 50:50 power splitters/couplers | \n\n
| \nEL: 2.7 dB IL: 5.5 dB CR: 1.08 dB Dir: 16.8 dB | \n
Side polishing | \nTwo POF segment are bonded and polished until the core-cladding interface appears. | \n\n
| \n\n | NA | \n
Chemical etching | \nChemical solvents i.e. acetone, chloroform, methyl isobutyl ketone are used to taper the fiber | \n\n | \n
| \nNA | \n
Reflective body | \nDevice used to split the light is a cylindrical polymer rod. | \n\n | \n | IL: 4.3 dB | \n
The types of couplers/splitter, the advantages and the disadvantages.
The demands of couplers include low loss, easy to handle, reproducible coupling behavior, lower manufacturing costs, small dimensions, having thermal and mechanical stability, having low mode dependence and have good isolation between the inputs [5]. Common designations of couplers include 1 × 2, 2 × 2, 1 × N and N × N coupler. Types of couplers/splitters include butt coupler, core fusion coupler, bend coupler and core facet coupler [5].
\nFor coupling to happen using lapping tapered-fibers technique, the two waveguides must be very close so that there is modal overlap, and the coupling coefficient is not zero. The wave is mainly confined within the core thus it is not possible to have wave coupling between fibers by just putting together two fibers side by side. Therefore, a core in one fiber must be very close to the core of another fiber or the propagating wave must extend far outside the core. One of the simple methods is to melt and fused the fiber together. By fusing and tapering the core together, this causes the dimension of the fiber core to be very small, thus the V number (mode number) is small.
\nTherefore, the propagating waves in the fiber extend far outside the core and coupling occurs according to coupling theory. By properly controlling the dimension of the fiber in the coupling region, a desired ratio of power coupling can be obtained [10]. If the two fibers are identical in the coupling region, both propagating waves will couple or split the same ratio of power from one fiber to another as shown in Figure 2.
\nLapped fiber coupler with particular lapping length and radiated modes.
Most of the existing 1 × 2 splitters only provide one or two fixed splitting ratios. Lapping technique provides the potential of producing multiple splitting ratios by adjusting the coupling length between the two lapping fibers and bending at certain angle. Due to this flexibility of adjusting the coupling length this work is focused on using lapping technique to develop this splitter. In order to produce multiple splitting ratios by bending and tapering, new platform is required to bend the fibers at certain angle and coupling length so that different coupling or splitting behavior or rays will give different splitting ratios. Apart from lapping the fiber at particular length and diameter, certain amount of force is exerted upon the splitter in order to minimize the macro-gap between the fibers. Since parameter of force is also included, study of coupling efficiency between the two lapping curved surfaces with certain amount of load is based on Coupled Mode Theory (CMT) and Hertz’s Law. No studies have been done in analyzing the coupling efficiency between the two lapping fibers based on the integration of CMT and Hertz’s Law. The coupling efficiency is analyzed when distance, coupling length and fiber diameter is varied.
\nAb-Rahman et al. has shown the fabrication of POF coupler/splitter using fusion technique where two POF are melted together and fused to developed N × N coupler/splitter [11]. The modififed coupler/splitter can be extended into demultiplexer. A novel fused POF splitter fabricated by fusion technique is an effective transmission media to split and recombine a number of different wavelengths which represents different signals. The demultiplexer device using different thin film having different colors to filter wavelength and optical splitter that provide optimal results when applied to the data transmission systems [12]. Although fused technique is easy, however, novel approach to develop the splitter is difficult to find. Thus, lapping technique using geometrical blocks are used to develop a directional coupler/splitter.
\nThere are some methods already done by researchers in order to fabricate coupler/splitters such as fusion between two or more fibers. One of the effective methods is tapering. Tapering can be done for example by technique of stretching fiber whilst it is heated under flame [13], and the other method is by chemical etching. The chemical used, acetone, is safe and harmless and it is effective to remove the cladding layer in certain time. Although tapering may change the physical fiber structure of the fiber itself, however, optical properties mostly remain the same. Due to the core being eliminated, the modes contained in the fiber will be radiated. The radiation of modes may be applied to this study that utilizes couple mode theory.
\nPMMA is dissolved using organic solvents such as acetone and methyl isobutyl ketone (MIBK) in order to remove the polymer in concentric layers as required. Research done by Merchant et al. [13] shows that by using pure acetone without any dilution in water can be used to efficiently remove the cladding layer of PMMA POF. The method requires no tension to be applied on fiber under etching process so as to prevent brittle stress fracture from occurring and break the fiber. The fiber should be supported in a curve and de-stressed fiber is supported in a straight line. Two to four drops of acetone are applied unto lint-free tissue and it is rotated along the region. The exposed core can be detected as the fiber is decreased in surface friction. Isopropyl alcohol is used to neutralize the solvent and leave the exposed core clean and grease-free. Once the region has been washed, it will return to PMMA physical and chemical properties. Another alternative method is by immersing the fiber into solution containing suitable mixture of organic solvent and water. Even when the solvent is diluted with 20% of distilled water, the brittle property of the fiber during the etching process remain. The fiber region that immerses in the solvent will be uniformly etched producing a linear waist region.
\nBy tapering the multimode optical fiber cladding, higher modes of the fiber are removed while some other modes are redistributed when light source is propagating along the fiber. As the tapered section is developed, the evanescent field and proportion of total power within this field increases in the affected region.
\nTapering the fiber can reduce the diameter as shown in Figure 3 which can filter high-order modes in the fiber and create an effective reduction in numerical aperture which can be an advantage for optical sensor. POF tapers require no alignment and have constant attenuation of low-order modes. The modal redistribution length of POF is a few hundred meters and so the effect of tapers is local to that distance [13].
\nThe waist of the etched region is tapered.
Polishing technique is one of the methods [14, 15, 16] to reduce or eliminate the cladding so that the modes that propagate along the fiber may be radiated out due to evanescent wave theorem. Due to polishing effect, which is rough surfaces of the polished fiber, that may lead to increase in losses, therefore, some treatment has to be done. UV curing adhesive having similar refractive index may be used to bridge the gap between the polished fiber in order to reduce the losses. The efficiency of the coupling light ranging up to 50% and the insertion loss is less than 5 dB [17]. Although it was simple, the limitation occurs when polishing leaves a rugged surface of the fiber. Thus, in this study, the polished surface is done by side etching the surface as shown in Figure 4 in order to minimize the losses of surface.
\nSide-polished of a fiber.
Losses in optical fiber can be traced back by absorption, scattering or bending. Although losses are not a preferred performance parameter, however, it can be utilized into something useful such as coupling of modes of the bent dielectric waveguide [18]. One of the concepts applies is loss due to macro-bending of tapered bent fiber. The smaller the bending radius, the higher the losses will be [19].
\nAt certain bending radius, which is known as critical radius, the loss is very high where total internal reflection an electromagnetic disturbance which is known as evanescent wave penetrate the reflecting interface. The rate of the propagating evanescent wave will reduce when reflection interface is no longer exists because it cannot propagate in the medium of lower refractive index.
\nWhen a light ray hits core-cladding interface, one of the rays will be refracted at the cladding interface and either the ray will be reflected back or refracted with some amount of power [20] while the other ray will propagate at inner core interface. More losses may be observed if bending starts to get smaller in radius where more rays will be refracted so thus the amount of power transferred at the cladding.
\nRefraction can also cause leaks of rays at the core-cladding interface. Electromagnetic tunnelling at the core-cladding interface is due to the cross section of the curvature. However, the leakage occurring at the tunnelling modes are slower as compared to refracting modes [8]. Some number of rays are not bounded by the core which results in propagating in the cladding region. This is known as the cladding modes and coupling can occur with the higher-order modes of the core resulting in loss of the core power.
\nThere are few benefits of bending losses which are based on either the increase in the attenuation or on making use of the light which escapes from the optic fiber. One of the examples of making use the attenuation experienced by the fiber as it bends is fiber optic pressure sensor where a particular length of bare fiber is placed between two rugged pieces of rubber while the fiber is placed in straight line. A light detector is placed on the end side. When a step pressures the rubber, bends is created, and light intensity is detected, and the alarm went off. On the other hand, an active fiber detector uses light that escapes from the bent fiber. A fiber is placed between jaws of tool and when the fiber is stepped on and pressure exerted upon it, a sharp bend is created by the jaw and some light escapes and detected by the photocell and switch on a warning light [21].
\nSimple analytical analysis is studied to analyze the developed coupler using two important concepts which are Coupled Mode Theory and Hertz’s Law. Simple coupled mode theory derived by Ogawa [22] analyzes the coupling theory between two parallel multimode step-index fibers and obtaining the coupling efficiency. Hertz’s law in the other hand deals with contact mechanics where when load existed between two surfaces that relates to elliptical point contacts and the amount of force on the fibers determines the coupling length of the two fibers.
\nOptical directional couplers can be described by coupling length and coupling coefficient as described in Coupled Mode Theory (CMT). The study of CMT has been done among researchers; however, the study of multimode is quite complicated compared to fiber having one or few modes [23]. Thus, this study focuses mainly on two multimode parallel fiber cores using simplified Coupled Mode Theory to find the coupling coefficient and coupling efficiency derived by Ogawa [22]. The coupling efficiency describes the total power of coupling between the two fibers depending on the distance, fiber core thickness and length of the contact region [24].
\nA multimode coupler or tap coupler is an important component in any short distance communication system. In multimode fiber, it is not easy to evaluate the coupling process between hundreds of modes. Ogawa [22] derived a simplified expression for coupling efficiency between two identical, parallel, step-index multimode fibers which can expand to all modes with a condition that the two fibers are touching each other. Ogawa [22] agrees that the distance between the two fibers affects the coupling efficiency among other considered parameters.
\nThe higher the modes launched at the input of the fiber, the higher the coupling efficiency will be. Higher order modes leakage may result in higher coupling in short lengths [25].
\nThe simplified coupling coefficient given by Ogawa [22] describes that when distance over both radii of core or distance,
Where a = radius of core
\nk = \n
nco = refractive index of core
\nncl = refractive index of cladding
\nd = distance between the two fibers
\ni = \n
N = number of modes in step-index multimode fiber
\nCoupling coefficient reaches maximum when
Elliptical contact area forms when two 3-dimensional bodies, each with orthogonal radii of curvature come into contact [26]. When force, F is applied between two curved surfaces, compression happens at the beginning of the contact and theoretically a flat surface is formed between them. The area is tangential to the surfaces of the two contacts and it is perpendicular to the line of action of load, F [27].
\nThe radius of the contact area is given by Eq. (2):
\nwhere
The depth of indentation ‘d’ is related to the maximum contact pressure by Eq. (3):
\nwhere
where
The size of the circular contact increases weakly with increasing load P and relative radius but decreases weakly with increasing contact modulus. The maximum pressure is 1.5 time the mean pressure and occurs at the center of the contact area [27].
\nDirectional coupler is a passive device where modes exchange between two waveguides that is placed closed to each other. Due to radiation and phenomenon of evanescent wave, some of the power will be transferred to an adjacent guide due to coupling. The factors that contributed to the power or modes exchange between the two parallel fibers are the force exertion and the length of lapping fibers. When two guides are parallel to each other, coupling coefficient is constant and the power launched into one guide will alternate back and forth between the two guides as long as they are close [28].
\nLapping technique is the method used in the study where two tapered fibers with certain thicknesses
Acetone is a harmless chemical solvent that is used to etch or taper the cladding layer at certain thickness or diameter. The duration of the etching process took around 30 minutes to 120 minutes. Depending on the time of the etching process, the diameter of the tapered fiber will vary. If the cladding layer is decreased, the transfer or power between the lapping fiber will occur. In some cases, the tapering not only causes the cladding layer to be stripped off entirely, but also affect the region where the lapping does not take place which in the other hand resulting to extra losses of the coupler/splitter. Therefore, a platform is developed where mechanical blocks with certain radii will be used together with the tapered fibers having similar refractive index of the fiber that will replace the refractive index of the etched cladding layer.
\nThe varied bending radii,
The preparation of the fibers includes preparing the fiber strands of 300 mm long, etching process and side polishing process. Basically, each of the fiber strands was prepared using Mitsubishi Eska Polymethil Methacrylic (PMMA) step-index polymer optical fiber.
\nThe process of etching process is done on polymer optical fiber which has diameter core of ø = 980 μm and diameter cladding of ø = 20 μm thick as shown in Figure 5. Chemical solvent that is acetone is used in this study in order to remove cladding layer. Etching process as shown in the figure takes between 30 minutes to 120 minutes to stripped off the cladding layer as intended. Due to the effectiveness of the solvent to impair and remove the cladding layer as reported by the research done by Merchant et al., [29], pure 100% acetone is used in the experiment without any additional liquid or solvent involved or modification the concentration of the solvent.
\nEtching done by stress-free bending.
\nFigure 6 shows the light transmitting over an etched area between the two blue marks shows faded red light along the area. This fiber has been properly etched and contains the transmitting light with low leakage. Some of the modes are radiated out due to the cladding layers are etched over some duration of time. Therefore, as can be seen in the figure, at the etched region, LED light of wavelength 665 nm are radiated out. The etched fibers are used to develop directional couplers by using geometrical blocks. Etched fibers or denoted as coupler A is fixed unto the circular blocks and they are lapped together. Wavelength of red LED, 665 nm with input power of 16.0 μW is used as the light source. In Figure 7, a schematic of bent fibers lapping at certain length with tapered cladding can be seen. Light source having 665 nm wavelength is used to send signal in port a, and the power output are measured at the end of port b, c, and d. The measurements are taken at the end of the three output ports in order to analyze the losses due to tapered cladding and force exertion between the two lapping fibers.
\nLight transmission in properly etched fiber.
Schematic of coupler using fibers that were etched.
There are many efforts done by researchers on developing an optical directional coupler using various techniques as discussed previously. In this work, new technique of developing 1 × 2 optical coupler is fabricated using mechanical techniques where geometrical blocks namely circular blocks of several radii, elliptical blocks of several radii with external forces exerted upon the blocks and fibers and semi-elliptical blocks with spring embedded are used where a pair of etched fibers is placed between them and bent as according to the bending radius of the blocks. Then at input port,
\nFigure 8 shows the setup of circular blocks where the fibers length are around 30 cm using Mitsubishi Rayon Eska POF. The end of each fiber is connected with power meter of type AF OM 210A.
\nCircular blocks platform with a pair of tapered fibers bent according to the bending radius of the blocks and input of 650 nm is inserted into one of the input and the output power is recorded.
\nTable 2 shows the optimum splitter at each circular blocks pair. Splitter of coupling diameter,
Rc (mm) | \nDc (mm) | \nSRc (%) | \nEL (dB) | \nIL (dB) | \n
---|---|---|---|---|
25–25 | \n0.92–0.90 | \n2.41 | \n6.00 | \n22.00 | \n
30–40 | \n0.85–0.75 | \n2.00 | \n3.00 | \n20.00 | \n
35–27 | \n0.85–0.75 | \n2.30 | \n3.00 | \n19.60 | \n
30–20 | \n0.92–0.90 | \n2.60 | \n6.00 | \n22.00 | \n
52–40 | \n0.85–0.75 | \n1.00 | \n3.50 | \n23.00 | \n
28–26 | \n0.85–0.90 | \n1.30 | \n2.70 | \n21.00 | \n
28–22 | \n0.85–0.75 | \n2.50 | \n3.50 | \n19.60 | \n
28–23 | \n0.85–0.75 | \n1.70 | \n3.80 | \n21.00 | \n
38–34 | \n0.85–0.90 | \n1.00 | \n2.80 | \n22.00 | \n
38–37 | \n0.85–0.75 | \n1.80 | \n3.80 | \n21.00 | \n
Splitters with optimum SR, EL and IL for each bending radius.
Although splitter of
Excess losses for each coupler/splitter of different core-cladding Thickness,
At throughput port as shown in Figure 10, splitters of
Insertion losses at throughput port for each coupler/splitter of different core-cladding thickness,
\nFigure 11 shows the average splitting ratios when external load is exerted upon the splitters fitted into circular blocks. Splitting ratios show a slight decreased when external load is exerted upon the splitters of etching length,
Average splitting ratio for normal and external load unto splitter of varied etching length fiber splitters using varied combination of circular blocks.
The coupling efficiency from experimental values are calculated by
\nThe efficiency of coupling length,
Efficiency values at coupling Length.
Analytically, the result shows the coupling efficiency of core radius of 0.75 mm at coupling length extends from 0 mm to 20 mm. The distance,
It is observed that the pattern of the coupling efficiency of experimental values and analytical values is similar as shown in Figure 13, however, analytically the ideal simulated wave shows higher percentage of efficiency compared to the values of the efficiency of the experiment. The average difference of efficiency between analytical and experimental values is between 7% to 22%. The differences between the values are due to several factors. Due to the varied bending angle,
Similar pattern of efficiency is observed for both analytical and experimental values at specified coupling length.
New technique of developing an optical coupler using POF and mechanical platform using lapping technique is discussed and analyzed. The device fabricated is flexible since the splitter does not only give one particular splitting ratio desired, but it can be customized using different blocks of bending radius and several pair of fibers with different core-cladding thickness. The different pair of fibers can be matched with different pair of blocks in order to obtain particular splitting ratio for different applications. The implementation is simple where the blocks need to be placed on the platform where spring-like component will force the blocks to hold the fiber pairs close in proximity. Analysis of efficiency between experimental values of splitters and values obtained by simulated analytical values are compared where similar pattern of efficiency behavior is observed for the splitters which shows that the splitter is good to be used.
\nThe effect of different angle of fiber bending integrates with different taper length and core diameter with force exertion is studied and analyzed in this study. Optimum results of splitting ratios is obtained by having bending radius between 30 mm to 50 mm, taper length between 4 mm to 20 mm, core thickness between 0.88 mm to 0.77 mm, coupling length between 4 mm to 10 mm and 18 mm to 22 mm and pressure not less than 3.0 lbF. The variation of the parameters leads to different coupling characteristics thus resulting in various splitting ratios and losses. Therefore, for different parameter values, particular values of other parameters have to be considered.
\nThe maintenance of the device is also simple. The fiber pairs can be used continuously and interchanged with other fiber pairs. The fibers need to be changed with new ones only when the fiber is broken. In this case, since POF itself is very flexible, thus, the flexibility and maintenance of the fibers are quite reliable. The platform and the blocks are made of strong material that is hardly broken even they are dropped several times. Even in high temperature and heat, POF melting point is around 80\n
The developed device can be innovated into a ‘DIY’ kit where the installation of the passive device will be easy and customer friendly. Different values of splitting ratios are able to be achieved thus give the advantage of different applications for the users. Moreover, since the device may provide different values of splitting or coupling ratios in one kit, users may no longer need to spend extra on purchasing another splitter/coupler. This device is inexpensive and green technology based due to materials used in the development and utilization.
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Biodiesel lessens net carbon dioxide emissions up to 78% with reference to conventional fuel. That is the reason for the improvement of new and operative solid catalysts necessary for inexhaustible and efficient fuel production. Homogenous base catalysts for transesterification is risky in light of the fact that its produces soap as byproduct, which makes difficult issues like product separation and not temperate for industrial application. In comparison, heterogeneous process gives higher quality FAME which can be effectively isolated and facilitate costly refining operations that are not required. A focus of this review article is to study and compare various biodiesel synthesis techniques that are being researched. The catalytic strength of numerous heterogeneous solid catalysts (acid and base), specially earth and transition metal oxides were also appraised. It was observed that catalytic proficiency relied upon a few factors, for example, specific surface area, pore size, volume and active site concentration at catalyst surface. This review article will give assistance in assortment of appropriate catalysts and the ideal conditions for biodiesel generation.",book:{id:"6784",slug:"biofuels-state-of-development",title:"Biofuels",fullTitle:"Biofuels - State of Development"},signatures:"Sadia Nasreen, Muhammad Nafees, Liaqat Ali Qureshi, Muhammad\nShahbaz Asad, Ali Sadiq and Syed Danial Ali",authors:[{id:"216103",title:"Dr.",name:"Sadia",middleName:null,surname:"Nasreen",slug:"sadia-nasreen",fullName:"Sadia Nasreen"},{id:"216918",title:"Dr.",name:"Muhammad",middleName:null,surname:"Nafees",slug:"muhammad-nafees",fullName:"Muhammad Nafees"},{id:"228115",title:"Prof.",name:"Liaqat",middleName:null,surname:"Qurashi",slug:"liaqat-qurashi",fullName:"Liaqat Qurashi"}]},{id:"67131",doi:"10.5772/intechopen.84995",title:"Different Pretreatment Methods of Lignocellulosic Biomass for Use in Biofuel Production",slug:"different-pretreatment-methods-of-lignocellulosic-biomass-for-use-in-biofuel-production",totalDownloads:2177,totalCrossrefCites:13,totalDimensionsCites:39,abstract:"Lignocellulosic biomasses are carbon neutral and abundantly available renewable bioresource material available on earth. However, the main problem that hinders its frequent use is the tight bonding within its constituents that include cellulose, hemicellulose, and lignin. The selection of pretreatment process depends exclusively on the application. Various pretreatment processes are primarily developed and utilized in effective separation of these interlinked components to take maximum benefit from the constitutes of the lignocellulosic biomasses especially for the production of biofuel. The major pretreatment methods include physical, chemical, thermophysical, thermochemical, and biological approaches. Various aspects of these different pretreatment approaches are discussed in this chapter.",book:{id:"7608",slug:"biomass-for-bioenergy-recent-trends-and-future-challenges",title:"Biomass for Bioenergy",fullTitle:"Biomass for Bioenergy - Recent Trends and Future Challenges"},signatures:"Muhammad Nauman Aftab, Irfana Iqbal, Fatima Riaz, Ahmet Karadag and Meisam Tabatabaei",authors:null},{id:"66095",doi:"10.5772/intechopen.83569",title:"Agro-Industrial Waste Revalorization: The Growing Biorefinery",slug:"agro-industrial-waste-revalorization-the-growing-biorefinery",totalDownloads:1625,totalCrossrefCites:18,totalDimensionsCites:34,abstract:"Agro-industrial residues have been the spotlight of different researches worldwide, due to some of their constituents being raw material to generate a diversified variety of industrial products. Nowadays, this situation keeps prevailing and will increase continuously in the future. In the agroindustry, diverse biomasses are subjected to distinct unit processes for providing value to different waste materials from agriculture, food processing, and alcoholic industries. In this chapter, we reported an updated survey of different renewable organic materials that including agricultural wastes can be converted to bioenergy. Similarly, these wastes encrypt different bioactive compounds with an excellent nutraceutical functions and with high adding value. In addition, biocomposites can be elaborated using fibers from wastes with a wide variety of applications in the automotive and packaging industry. Vinasses derived from tequila industry in Mexico represent a lot of potential to extract biocompounds, and we propose a process to obtain them. A perspective of market trend is mentioned in this chapter for compounds derived from agro-industrial wastes. Adding value to those agro-industrial wastes can provide the reduction of negative impact emission, discharge, or disposal, solves an environmental problem, and generates additional income.",book:{id:"7608",slug:"biomass-for-bioenergy-recent-trends-and-future-challenges",title:"Biomass for Bioenergy",fullTitle:"Biomass for Bioenergy - Recent Trends and Future Challenges"},signatures:"Flora Beltrán-Ramírez, Domancar Orona-Tamayo, Ivette Cornejo-Corona, José Luz Nicacio González-Cervantes, José de Jesús Esparza-Claudio and Elizabeth Quintana-Rodríguez",authors:null},{id:"59749",doi:"10.5772/intechopen.75111",title:"Prospective Biodegradable Plastics from Biomass Conversion Processes",slug:"prospective-biodegradable-plastics-from-biomass-conversion-processes",totalDownloads:2345,totalCrossrefCites:15,totalDimensionsCites:30,abstract:"The biomass energy source has been a promising renewable alternative for fossil fuels and their inevitable environmental impacts on Earth’s life, from which the greenhouse gas (GHG) emissions and the environment pollution followed by consequent ecosystem imbalance are major concerns. Biofuels and bioplastics are well-known examples of renewable products obtained from biomass that has shown increasing potential to succeed the conventional fuels and plastics. However, biofuels and especially bioplastics have faced their main hindrance in their uncompetitive costs. Furthermore, the “drop-in” plastics are the market leaders, which reduce the carbon footprint but continue to state the biodegradability concern attributed to most of plastic products, the packaging sector. This chapter outlines the common features and feedstocks of biofuels and bioplastics aiming to support their associated production set toward the bio-based and biodegradable poly(lactic acid) (PLA) and polyhydroxyalkanoates (PHAs) as promising models with fast-growing production capacity forecasted for the next years and biodegradable solution for short-lived and disposable plastic materials.",book:{id:"6784",slug:"biofuels-state-of-development",title:"Biofuels",fullTitle:"Biofuels - State of Development"},signatures:"Fabrício C. de Paula, Carolina B.C. de Paula and Jonas Contiero",authors:[{id:"193454",title:"Prof.",name:"Jonas",middleName:null,surname:"Contiero",slug:"jonas-contiero",fullName:"Jonas Contiero"},{id:"220984",title:"Dr.",name:"Fabrício",middleName:null,surname:"Coutinho De Paula",slug:"fabricio-coutinho-de-paula",fullName:"Fabrício Coutinho De Paula"},{id:"222270",title:"BSc.",name:"Carolina",middleName:null,surname:"Bilia Chimello De Paula",slug:"carolina-bilia-chimello-de-paula",fullName:"Carolina Bilia Chimello De Paula"}]},{id:"67397",doi:"10.5772/intechopen.86701",title:"Lignocellulosic Ethanol: Technology and Economics",slug:"lignocellulosic-ethanol-technology-and-economics",totalDownloads:1675,totalCrossrefCites:10,totalDimensionsCites:20,abstract:"The accelerated global warming calls for fast development of solutions to curb excessive Greenhouse gas emission. Like most of other forms of renewable energy, lignocellulosic ethanol can help the human beings mitigate the climate deterioration and gain independence from fossil fuels. This chapter gives a survey of bioethanol production in the U.S. and world, describes classifications of three generations of bioethanol, provides an overview of all the stages of currently adopted process for the second-generation bioethanol production, briefs on new development on enzymes for hydrolysis and fermentation and new processes for ethanol generation, summarizes on recent life-cycle assessments of greenhouse gas emission and techno-economic evaluation of ethanol production. To sustain the infant cellulosic ethanol industry, substantial improvement in the following areas need to happen in a timely manner: (1) Effective and low-cost biomass pretreatment method, (2) efficient fermentation of all sugars released during the pretreatment and hydrolysis steps, (3) development of enzymes that tolerate various inhibitors including monosaccharides (mainly glucose) and ethanol, and (4) heat-tolerant fermentation microbes and enzymes for efficient simultaneous saccharification and fermentation. Genetic engineering is expected to play a key role in addressing most of the issues in these areas.",book:{id:"7828",slug:"alcohol-fuels-current-technologies-and-future-prospect",title:"Alcohol Fuels",fullTitle:"Alcohol Fuels - Current Technologies and Future Prospect"},signatures:"Cheng Zhang",authors:null}],mostDownloadedChaptersLast30Days:[{id:"66307",title:"Bio-hydrogen and Methane Production from Lignocellulosic Materials",slug:"bio-hydrogen-and-methane-production-from-lignocellulosic-materials",totalDownloads:2934,totalCrossrefCites:5,totalDimensionsCites:7,abstract:"This chapter covers the information on bio-hydrogen and methane production from lignocellulosic materials. Pretreatment methods of lignocellulosic materials and the factors affecting bio-hydrogen production, both dark- and photo-fermentation, and methane production are addressed. Last but not least, the processes for bio-hydrogen and methane production from lignocellulosic materials are discussed.",book:{id:"7608",slug:"biomass-for-bioenergy-recent-trends-and-future-challenges",title:"Biomass for Bioenergy",fullTitle:"Biomass for Bioenergy - Recent Trends and Future Challenges"},signatures:"Apilak Salakkam, Pensri Plangklang, Sureewan Sittijunda, Mallika Boonmee Kongkeitkajorn, Siriporn Lunprom and Alissara Reungsang",authors:null},{id:"72179",title:"Production Pathways of Acetic Acid and Its Versatile Applications in the Food Industry",slug:"production-pathways-of-acetic-acid-and-its-versatile-applications-in-the-food-industry",totalDownloads:1679,totalCrossrefCites:3,totalDimensionsCites:10,abstract:"Acetic acid is a commodity chemical with the global demand of approximately 15 million tons per year with several applications in the chemical and food industry. The production of acetic acid can be widely categorized into chemical and fermentative routes, with the chemical route being the predominant one in the current industrial practice. In this chapter, we have reviewed the most recent developments in acetic acid production and applications over past two decades, including process intensification and catalysis by keeping the main emphasis on process sustainability. Acetic acid is used in several industrial sectors such as chemical, pharmaceutical, textile, polymer and paints, food and beverages. Furthermore, acetic acid has several applications in food industry and is traditionally known as vinegar. In addition, it is an acidulant, which is used to give a characteristic flavor profile to food. It can be used for microbial decontamination of meat and as a mild descaling agent in the food industry. More recently, acetic acid is reported to be used as an antimicrobial edible food coating agent. The diversified food culture has a significant demand in the development of such kind of innovation and acetic acid can be an efficient solution.",book:{id:"10127",slug:"biotechnological-applications-of-biomass",title:"Biotechnological Applications of Biomass",fullTitle:"Biotechnological Applications of Biomass"},signatures:"Gunjan Deshmukh and Haresh Manyar",authors:[{id:"316193",title:"Dr.",name:"Haresh",middleName:null,surname:"Manyar",slug:"haresh-manyar",fullName:"Haresh Manyar"},{id:"316199",title:"Dr.",name:"Gunjan",middleName:null,surname:"Deshmukh",slug:"gunjan-deshmukh",fullName:"Gunjan Deshmukh"}]},{id:"60944",title:"Hydrogen Generation by Water Electrolysis",slug:"hydrogen-generation-by-water-electrolysis",totalDownloads:3949,totalCrossrefCites:10,totalDimensionsCites:18,abstract:"Hydrogen is a promising energy vector for the future. Among the different methods of its production, the electrolysis of water has attracted great attention because it is a sustainable and renewable chemical technology. Thus, hydrogen represents a suitable energy vector for the storage of intermittent energies. This chapter is devoted to the hydrogen generation by water electrolysis as an important part of both existing and emerging industrial electrochemical processes. It aims to give an insight into the theoretical foundations of the operating principles of different types of electrolyzers. Also, it is developed in this chapter, the thermodynamic and kinetic aspects of the reactions taking place at the electrodes of water electrolysis. The evolution reaction of hydrogen has a rapid kinetics, and thus, the polarization of the cathode is not critical. On the other hand, the evolution reaction of oxygen is characterized by a very slow kinetics and is thus responsible for most of the overvoltage in the electrolysis of water. The most important technologies of water electrolysis are addressed: alkaline electrolysis, proton exchange membrane electrolysis, and solid oxide high-temperature electrolysis.",book:{id:"6665",slug:"advances-in-hydrogen-generation-technologies",title:"Advances In Hydrogen Generation Technologies",fullTitle:"Advances In Hydrogen Generation Technologies"},signatures:"Youssef Naimi and Amal Antar",authors:[{id:"232378",title:"Dr.",name:"Youssef",middleName:null,surname:"Naimi",slug:"youssef-naimi",fullName:"Youssef Naimi"},{id:"236905",title:"Mrs.",name:"Amal",middleName:null,surname:"Antar",slug:"amal-antar",fullName:"Amal Antar"}]},{id:"74066",title:"Comparative Analysis of Bioethanol Production from Different Potential Biomass Sources in the Philippines",slug:"comparative-analysis-of-bioethanol-production-from-different-potential-biomass-sources-in-the-philip",totalDownloads:709,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"To pursue the continuous implementation of the bioethanol blending mandate by the Philippine Biofuels Law, part of the roadmap of the National Biofuels Board (NBB) through the Department of Energy (DOE) is to find a sustainable feedstock. This is due to the deficit in locally produced bioethanol as there is an insufficient supply of currently used feedstock, sugarcane. There are several biomasses available in the country with components viable for ethanol fermentation. Aside from sugarcane, these include sweet sorghum and cassava (first-generation), rice straw and corn stover (second-generation), and macroalgae (third-generation). Among which, sweet sorghum can be considered as the best complementary feedstock to sugarcane as its syrup can be directly fermented to produce bioethanol. Considering its maximum bioethanol potential yield of 100 L/ton for two croppings annually, a comparably low production cost of PhP 36.00/L bioethanol was estimated, competitive enough with the PhP33.43/L bioethanol from sugarcane. Aside from finding a promising feedstock, the bioethanol production volume in the country must be increased to meet the demand through either working on the optimum processing conditions to increase the capacity utilization from the current 77.9% or through installation of additional distilleries.",book:{id:"10379",slug:"bioethanol-technologies",title:"Bioethanol Technologies",fullTitle:"Bioethanol Technologies"},signatures:"Kristel M. Gatdula, Rex B. Demafelis and Butch G. Bataller",authors:[{id:"291875",title:"M.Sc.",name:"Kristel",middleName:"Manzanero",surname:"Gatdula",slug:"kristel-gatdula",fullName:"Kristel Gatdula"},{id:"328349",title:"Dr.",name:"Butch",middleName:null,surname:"Bataller",slug:"butch-bataller",fullName:"Butch Bataller"},{id:"328350",title:"Dr.",name:"Rex",middleName:null,surname:"Demafelis",slug:"rex-demafelis",fullName:"Rex Demafelis"}]},{id:"73832",title:"Biomass Conversion Technologies for Bioenergy Generation: An Introduction",slug:"biomass-conversion-technologies-for-bioenergy-generation-an-introduction",totalDownloads:1007,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Over the last century, there has been increasing debate concerning the use of biomass for different purposes such as foods, feeds, energy fuels, heating, cooling and most importantly biorefinery feedstock. The biorefinery products were aimed to replace fossil fuels and chemicals as they are renewable form of energy. Biomass is a biodegradable product from agricultural wastes and residues, forestry and aquaculture. Biomass could be sourced from a variety of raw materials such as wood and wood processing by-products, manure, fractions of organic waste products and agricultural crops. As a form of renewable energy, they have the advantages of easy storage, transportation, flexible load utilization and versatile applications. The aim of this study is to provide an overview for thermochemical and biochemical biomass conversion technologies that were employed currently. Attention was also paid to manufacture of biofuels because of their potentials as key market for large-scale green sustainable biomass product.",book:{id:"10127",slug:"biotechnological-applications-of-biomass",title:"Biotechnological Applications of Biomass",fullTitle:"Biotechnological Applications of Biomass"},signatures:"Abdurrahman Garba",authors:[{id:"245271",title:"Dr.",name:"Abdurrahman",middleName:null,surname:"Garba",slug:"abdurrahman-garba",fullName:"Abdurrahman Garba"}]}],onlineFirstChaptersFilter:{topicId:"144",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:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:320,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:17,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. 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",coverUrl:"https://cdn.intechopen.com/series/covers/22.jpg",latestPublicationDate:"June 27th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"356540",title:"Prof.",name:"Taufiq",middleName:null,surname:"Choudhry",slug:"taufiq-choudhry",fullName:"Taufiq Choudhry",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000036X2hvQAC/Profile_Picture_2022-03-14T08:58:03.jpg",biography:"Prof. Choudhry holds a BSc degree in Economics from the University of Iowa, as well as a Masters and Ph.D. in Applied Economics from Clemson University, USA. In January 2006, he became a Professor of Finance at the University of Southampton Business School. He was previously a Professor of Finance at the University of Bradford Management School. He has over 80 articles published in international finance and economics journals. His research interests and specialties include financial econometrics, financial economics, international economics and finance, housing markets, financial markets, among others.",institutionString:null,institution:{name:"University of Southampton",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"86",title:"Business and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/86.jpg",isOpenForSubmission:!0,annualVolume:11970,editor:{id:"128342",title:"Prof.",name:"Vito",middleName:null,surname:"Bobek",slug:"vito-bobek",fullName:"Vito Bobek",profilePictureURL:"https://mts.intechopen.com/storage/users/128342/images/system/128342.jpg",biography:"Dr. Vito Bobek works as an international management professor at the University of Applied Sciences FH Joanneum, Graz, Austria. 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From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. 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He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"24",type:"subseries",title:"Computer Vision",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR",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",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11420,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null,series:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403"},editorialBoard:[{id:"1177",title:"Prof.",name:"António",middleName:"J. 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