**1. Introduction**

Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness, it is a heterogeneous disease commonly seen in childhood as a chronic airway disorder [1]. The latest prevalence of childhood asthma in the United States is 5.8% [2], while there is a lack of unified and comprehensive epidemiological survey in China, the prevalence of childhood asthma in China in recent years is about 4.90% through meta-analysis [3], which was higher than the prevalence of the Third National Childhood Asthma Epidemiological Survey of Chinese major cities in 2010 [4]. The research documents the association of immunity with the development of asthma, which is currently believed to be an airway inflammatory disease dominated by a Th2 type of immune response. Found throughout the body in cells, tissues, and body fluids, MicroRNAs are noncoding endogenous RNAs of 19 to 25 nucleotides in number, which base-pair with target gene mRNAs to regulate posttranscriptional expression of the target gene by silencing or blocking the target gene. MicroRNAs are nonspecific and can simultaneously regulate several target genes to fulfill biological roles [5–7]. Their involvement in asthma development has been proven, among others, through

the promotion of T cell differentiation toward Th2, the increase of Th2 cytokines, and the decrease of Th1 cytokine secretion [8–11].

Recent studies have highlighted the importance of type 2 innate lymphocytes (ILC2s) in the development of asthma [12, 13]. ILC2s are primarily generated from common lymphoid progenitors (CLPs) in bone marrow, where their maturation proceeds and contributes to intrinsic immunity and tissue repair. It is generally assumed that Th2 cells are the primary source of type 2 cytokines. In contrast, more studies have surfaced that ILC2s can also be a significant early contributor to type 2 cytokines and that such cells can be critical in both the initiation and effector phases of type 2 immunity. ILC2s trigger both the innate response to allergic inflammatory responses and the immune response to adaptive Th2 [14–16]. Experimental stimulation of ILC2s-deficient mice with allergens revealed that the mice did not produce a solid allergic inflammatory response in the lungs and that Th2 cell differentiation was impaired; however, the impaired Th2 cell differentiation was rescued by ILC2 transplantation [15]. Therefore, ILC2s are essential for Th2 cell-mediated allergic lung inflammation and can induce the differentiation of CD4+ T cells into Th2 cells. Furthermore, ILC2s and Th2 cells interact reciprocally during the type 2 immune response, with either the interaction of co-stimulatory molecules or in a direct cell–cell contact-dependent manner through soluble mediators, such as cytokines [17, 18]. In response to the Th2 polarizing cytokines IL-25 and IL-33, ILC2s rely on transcription factors, such as RORα and GATA3, to differentiate and mature [19, 20]. Similarly, n response to IL-4, Th2 cells also depend on transcription factors, such as GATA3, for differentiation and maturation. After the activation of both ILC2s and TH2, a significant amount of Th2 cytokines, IL-4, IL-5, and IL-13 would be produced of which IL-25 is constitutively expressed by clustered cells in the intestine and remains essential for ILC2s to remain stable, IL-25 induces IL-13 production by ILC2s, and IL-13 production by ILC2s and/or Th2 cells may conversely promote differentiation and expansion of clustered cells, creating positive feedback [15, 21, 22]. MiRNAs are increasingly known to regulate the activation of ILC2s and Th2 and Th2-related inflammatory factor production, leading to their involvement in the pathogenesis of asthma. Below is an overview of how miRNAs are involved in asthma development by mediating Th2 and ILC2s.

#### **1.1 Relation between MiRNAs and Th2 differentiation and homeostasis**

Th1 and Th2 are in relative homeostasis under normal physiological conditions, whereas an imbalance in the Th1/Th2 ratio and excessive secretion of Th2 cytokines contribute to the pathogenesis of allergic asthma. Most studies have documented that miRNAs are abnormally expressed and are strongly associated with disorders of the Th1/Th2 immune response in asthma [9, 10, 23, 24]. Up or down-regulation of miR-NAs can lead to increased secretion of Th2 cytokines or decreased secretion of Th1 cytokines. Up-regulated miRNAs in asthma include miR-21, miR-126, miR-221-3p [25], and miR-3162-3p [26]. Up-regulated miRNAs, including miR-451, miR-1165, miR-29b [27], and miR-135a [28], increased Th2 cytokine secretion include miR-146. As miRNAs can affect T cell differentiation, activation, and eosinophilic mast cell activation in allergic diseases, they could be used as a potential means to reduce Th2 inflammation from the altered genetic level and as noninvasive biomarkers for early prediction of asthma development. Of the many publications on how miRNAs regulate Th2 cells, a few of the most extensive studies are presented below.

### **1.2 MiR-155**

MiR-155 is an indispensable miRNA for functioning dendritic cells, T cells, B cells, and other immune cells. In the past, much attention has been focused on miR-155's involvement in pro-inflammation and Th1 immunity, and it is labeled as a "Th2 inhibitor" [29]. When compared to WT mice, for example, miR-155(−/−) mice showed significantly lower numbers of inflammatory cells in alveolar lavage fluid, which compromised the initiation of Th2 responses and reduced airway inflammation [8]. With further studies, however, miR-155 shows an integral contribution to allergic asthma. Therefore, in patients with asthma, there is decreased expression of miR-155 in peripheral blood CD4+ T cells, notably in severe asthma [30], meaning it is strongly associated with asthma severity, which may be achieved by directly targeting the IL-13 pathway suggesting that a strong correlation between miR-155 and asthma severity exists, which is probably attained by directly targeting the IL-13 pathway [31]. Compared to WT mice, miR-155-deficient mice have significantly reduced eosinophil content in alveolar lavage fluid after allergen stimulation [32], demonstrating that Mir-155 may gather more eosinophils during airway inflammation. In a similar vein, Kim constructed mouse models of miR-155 deficiency in T cells and identified lower levels of Th2 cytokines in alveolar lavage fluid and lower mucus secretion in the experimental group compared to the control group [33]. These findings recommend that miR-155 from T cells is essential for Th2 allergic airway inflammation as a crucial serological biomarker for asthma diagnosis and severity.

### **1.3 MiR-21**

Statistical studies of clinical data have found significantly higher levels of miR-21-3p and miR-487b-3p expression among the sera of children in the acute phase of food allergic reactions [34], presumably due to the targeted binding of lL-12 and miR-21-3p, which by down-regulating the former, could promote th2 inflammatory responses. Similarly, studies in an asthma rat model experiment revealed that miR-21-5p expression was significantly up-regulated, mainly in alveolar macrophages. MiR-21-5p produced by macrophages was confirmed by *in vitro* experiments to be targeted by the TGF-β1/Smad-signaling circuit to Smad7 after translocation to the airway epithelium for promoting EMT (epithelial-mesenchymal transition) [35], thereby enhancing airway remodeling leading to the development of asthma. Zhou demonstrated the involvement of mast cells in asthma development in an asthma model, where miR-21 was present in derived EV and could exacerbate the airway inflammatory response in mice via the DDAH1/Wnt/β-catenin axis [36]. Furthermore, a significant reduction in Th2 cytokine expression, an increase in IL-12 and IFN-γ secretion, and a reduction in cup cells in lung tissue were observed in miR-21-deficient asthmatic mice [37], which in turn attenuated airway inflammation as well as remodeling. From the above, miR-21 can be involved in the development and progression of asthma by promoting Th2 differentiation and airway remodeling through various inflammatory response signaling pathways. It can serve as a potential biomarker for allergic reactions.

### **1.4 let-7 family**

The let-7 family was found as a second microRNA, down-regulated in various tumors and also referred to as a tumor suppressor. However, there is some

controversy about the role of let-7miRNAs in asthma. IL-13, a critical Th2 cytokine, was also a direct target of let-7 microRNAs, some of which were suggested to play an anti-inflammatory role in the immune response. Manis agreed that let-7miRNAs possessed an anti-inflammatory action and concluded that let-7miRNAs reduced the inflammatory response by targeting the IL-13 3'UTR site, thereby lowering IL-13 levels through *ex vivo* experiments in asthma models [38]. Instead, Polikepahad has found a pro-inflammatory effect of let-7 in a mouse model of asthma [39], which may be associated with differences in experimental methods, making it even keener for further study by those to follow. In addition, it has been found that let-7 inhibitors can enhance the effect of airway smooth muscle on β2-receptor agonists by reducing β2-receptors downregulateion [40], which is more effective in asthma control.


**Author details**

Amir Goodarzi, Edwin Kulubya, Tejas Karnati and Kee Kim\* University of California Davis Department of Neurological Surgery, Sacramento, USA

\*Address all correspondence to<EMAIL_ADDRESS>
© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Cervicogenic Headache Hypothesis and Anterior Cervical Decompression as a Treatment Paradigm DOI: http://dx.doi.org/10.5772/intechopen.95931*


**4.2 In vivo evidence**

Several in vivo studies have investigated the effect of MSC treatment on tendon ECM composition and structure, as well as on tendon biomechanical parameters. In most of these studies, including an equine large animal study with a follow-up of 45 weeks, the ECM composition was improved by BMSC and ASC treatment, with higher expression of collagen I on gene and/or protein level [106, 114, 120, 122, 140]. Collagen III expression was found to be decreased after ASC implantation [110, 125, 126] but increased after BMSC implantation [106, 122]. Tenascin-C and decorin were found to be increased following BMSC and ASC treatment [112, 114, 140], and glycosaminoglycans were decreased after BMSC treatment [141]. Based on these data, MSCs appear to increase collagen I deposition in healing tendons. Furthermore, as an increase of human-specific collagen I and tenascin-C was demonstrated in a rat model after human ASC implantation, there is also some evidence that MSCs actively contribute to the synthesis of new ECM [114]. The contribution of collagen III, tenascin-C, and decorin synthesis/modulation to tendon healing is to be considered controversially, as illustrated above, and certainly depends on its balance with regard to other ECM components. Yet, beyond mere collagen I synthesis, BMSC and ASC have also repeatedly been shown to improve the structural organization of healing tendons, again including the study with a 45-week follow-up, as well as an experimental trial in horses with naturally occurring tendinopathy [108, 115, 121, 140, 141]. In conjunction with the synthesis and protection of desired ECM components such as collagen I, this could be due to active ECM remodeling and the contribution of synthesized small ECM molecules to collagen fibrillogenesis. Still, it should be acknowledged that some studies in the equine model could demonstrate only few compositional or structural improvements 5 months after ASC treatment [133, 137]. Moreover, despite generally improved ECM structure and collagen I synthesis, collagen II deposits and areas staining positive for

**79**

research.

*Mechanisms of Action of Multipotent Mesenchymal Stromal Cells in Tendon Disease*

alizarin red were found in BMSC-treated tendons [106], suggesting that erroneous MSC differentiation toward the chondrogenic and osteogenic lineage had occurred. Nevertheless, functional testing of BMSC- and ASC-treated tendons indicated an improvement of functional parameters in the majority of studies [107, 108, 112–115, 117, 119, 121, 122], which represents a beneficial effect that

So far, very few in vivo studies have investigated the effect of MSC on the presence and activation of matrix-remodeling enzymes and their endogenous inhibitors. In the equine model, MMP-13 activity was decreased 6 months after BMSC treatment [141], and MMP-3 gene expression was upregulated in the healing tendons 45 weeks after BMSC treatment [140]. Together, these results might suggest that collagen degradation could be inhibited while degradation of small ECM components is promoted. However, there is much overlap regarding MMP substrates [167], and other studies found no significant differences in MMP and TIMP expression due to ASC treatment [112]. Further studies have to substantiate

When MSCs were combined with tenogenic growth factors, conflicting results were reported. Treatment with ASC and GDF-5 decreased MMP-2 and TIMP-2 expression and resulted in inferior biomechanical properties compared to ASC treatment alone [112]. Treatment with ASC and BMP-12 promoted ECM degradation, which was interpreted as a side effect of the fibrin-based delivery vehicle [124], but improved tendon ECM regeneration when delivered as cell sheets without fibrin [123]. Interestingly, the latter study showed that this may have been mediated by modulating the ECM remodeling activity of macrophages [123]. A further study from the same group demonstrated beneficial effects of combined ASC and CTGF treatment, although not evaluating effects of ASC alone [125]. A different study showed that predifferentiated BMSC sheets, induced by stepwise stimulation with TGF-β1 and CTGF, resulted in superior tendon regeneration, including improved biomechanical properties than BMSC alone [54]. However, in this study, again, fibrin was used for delivery of noninduced cells, which may have contributed to the differences observed. Thus, although some data suggest that the additional use of growth factors potentiates the beneficial effects of MSC on ECM regeneration, more evidence supporting this hypothesis is required. It should also be acknowledged that growth factor supplementation might impair other regenera-

There is a substantial body of evidence that demonstrates the immunomodulatory potential of MSC. While not all underlying mechanisms have been elucidated in detail yet, it is well-understood that MSCs suppress T cell proliferation and promote the modulatory M2 macrophage phenotype [168]. Furthermore, small ECM molecules synthesized by the MSC, such as tenascin-C and decorin, could contribute to immunomodulation [163, 169]. Therefore, it is likely that immunomodulation plays an important role in MSC-based tendon therapies. Against that background, it appears surprising that relatively few studies have addressed the interplay between MSC and the immune system in the context of tendon disease. This may be due to the long-existing perception that inflammation is absent during most stages of tendon disease, which, however, has been changing [5, 170]. While so far existing findings are summarized in the following, immunomodulation in the context of tendon disease will remain a promising field of future

*DOI: http://dx.doi.org/10.5772/intechopen.83745*

can be attributed to ECM regeneration [3].

tive mechanisms of MSC at the same time [93].

**5. Immunomodulation**

this hypothesis.

### *Mechanisms of Action of Multipotent Mesenchymal Stromal Cells in Tendon Disease DOI: http://dx.doi.org/10.5772/intechopen.83745*

alizarin red were found in BMSC-treated tendons [106], suggesting that erroneous MSC differentiation toward the chondrogenic and osteogenic lineage had occurred. Nevertheless, functional testing of BMSC- and ASC-treated tendons indicated an improvement of functional parameters in the majority of studies [107, 108, 112–115, 117, 119, 121, 122], which represents a beneficial effect that can be attributed to ECM regeneration [3].

So far, very few in vivo studies have investigated the effect of MSC on the presence and activation of matrix-remodeling enzymes and their endogenous inhibitors. In the equine model, MMP-13 activity was decreased 6 months after BMSC treatment [141], and MMP-3 gene expression was upregulated in the healing tendons 45 weeks after BMSC treatment [140]. Together, these results might suggest that collagen degradation could be inhibited while degradation of small ECM components is promoted. However, there is much overlap regarding MMP substrates [167], and other studies found no significant differences in MMP and TIMP expression due to ASC treatment [112]. Further studies have to substantiate this hypothesis.

When MSCs were combined with tenogenic growth factors, conflicting results were reported. Treatment with ASC and GDF-5 decreased MMP-2 and TIMP-2 expression and resulted in inferior biomechanical properties compared to ASC treatment alone [112]. Treatment with ASC and BMP-12 promoted ECM degradation, which was interpreted as a side effect of the fibrin-based delivery vehicle [124], but improved tendon ECM regeneration when delivered as cell sheets without fibrin [123]. Interestingly, the latter study showed that this may have been mediated by modulating the ECM remodeling activity of macrophages [123]. A further study from the same group demonstrated beneficial effects of combined ASC and CTGF treatment, although not evaluating effects of ASC alone [125]. A different study showed that predifferentiated BMSC sheets, induced by stepwise stimulation with TGF-β1 and CTGF, resulted in superior tendon regeneration, including improved biomechanical properties than BMSC alone [54]. However, in this study, again, fibrin was used for delivery of noninduced cells, which may have contributed to the differences observed. Thus, although some data suggest that the additional use of growth factors potentiates the beneficial effects of MSC on ECM regeneration, more evidence supporting this hypothesis is required. It should also be acknowledged that growth factor supplementation might impair other regenerative mechanisms of MSC at the same time [93].


*<IP_ADDRESS>.1 Midwest caries ID probe*

It works on the principle of difference in the optical behaviour inside the tooth. The probe when placed on the tooth surface emits 635–880 nm wavelength and the light reflected from the surface of the tooth converts it to electrical signals [25].


**4. Discussion**

The results from this study of male tannery workers revealed that the workers were exposed to chemicals, leather dust, which contains chromium, and physical hazards. A substantial proportion of the tannery workers reported awareness of the health risks of the various tanning processes. The physical and cognitive

difficulty levels of the job in tanneries were like previous studies [8–10]. It is essential to mention here that there are very few studies conducted on tannery workers in the Indian context.

The results of our study validate the need for further efforts to minimize hazardous occupational health risks among tannery workers. However, findings depict tannery workers aged 36 years & above are less likely to be aware of the hazardous work environment, and malignant tissues involved in the tanning process, lack of protective equipment and safety devices showed a significant double risk for occupational health and injuries [11–14]. **Previous findings** agree with a study on salt workers found that there is a considerable gap between their knowledge and practices, along with protective measures [15]. Furthermore, a study conducted on chronic conditions, workplace safety, and job demands in Colorado revealed that non-provision of workplace safety led to employees' chronic health conditions and contributed to absenteeism and poor job performance. It also influences the physical and cognitive difficulties of the workers associated with the work [16]. Other factors also significantly affect the perceptions of health risks: age, education, religion, caste, media exposure, and standard of living index. Workers reported that they are aware that they have the chance of getting respiratory problems, skin complaints, eye-related, and gastrointestinal problems from the tannery. A substantial proportion of workers experienced severe conditions, such as humidity (69–88% of those surveyed), heat (69–84%), noise (78–87%); they had also got used to the smell of hides (51–63%). Comparable outcomes found by a study led in some developing countries concentrating on the upshot of work-related acquaintance to noise and heat on the health of the workers. Results portray that those who worked in the foundry had high thermal stress, high noise levels, high visual defects, high muscle cramps problem, high visual disability and describe non-use of protective equipment and poor occupational hygiene and safety measures were also affected the health problem among workers [17–20]. Our study recommended that leather dust exposure be reduced by providing gloves and masks and by installing a hood duct to provide better ventilation and removal of leather dust from the work area as also recommended by previous researches [21].

This research also suggested risks should be assessed for their potential consequences on health. Liquid effluents contain organic matter, chromium, sulfides, and solid wastes. A qualitative assessment of exposure showed that moderate to high exposure to chemicals and also contacted them. It has been reported from the literature that the workers on exposure to leather dust, which contains chromium in the protein-bound form, exhibited a higher mean concentration of urinary and blood chromium [8]. The workers engaged in beam housework, miscellaneous work, wet finishing, and dry finishing also reported moderate to high exposure to dust and ergonomic stressors. The use of safety gear was the highest in beam housework, followed by wet finishing, miscellaneous work, and dry finishing. This study also recognized a lack of awareness of the health risks in tannery operations and shortcomings in the use of preventive measures. Employers must raise awareness of health risks and ensure compliance with safety measures. But at the same time, qualitative results of focused group discussion with workers from small scale industries in Tanzania show high levels (>90%) of self-reported exposure to health problems, and low use of protective measures [22]. In continuation of the previous findings, a case study of electroplating sector workers in the United Kingdom showed that the employees had sound knowledge of the hazardous nature of chemicals used at the workplace [23].

**91**

*Responsiveness of Occupational Health Risk and Preventive Measures Practice by the Workers…*

An intervention study focused on prevention of work-related skin problems assessed the occupational health and safety among wet workers. The study found significant behavior change and fewer skin problems among workers in the intervention group as compared to the control group. The intervention was successful in enhancing knowledge and changing behavior [24]. Literature suggests most workers had an essential awareness of the existence of occupational health and safety legislation, but they were unaware of their legal responsibilities. They were found to

The findings of this study reveal that the tannery workers work in a very hazardous work environment and susceptible to health risks. Although, tannery workers are less aware of the health hazard involved in the tanning process and even not aware of the exposure to hazardous chemicals at the work place. Evidence from the qualitative measures of environmental exposure pointed out that they work in different activities at the tannery and having different exposures. Further, the study findings reveal that tannery workers are not utilizing the appropriate preventive measures as per the protocol. The outcomes of the study give a clear indication of the effect of the workstation environment on the health status of workers and require the use of adequate measures to improve the facilities and thereby the health status of tannery workers.

We have received ethical approval from the board. The Student Research Ethics Committee approved the study of the International Institute for Population Sciences Mumbai, India. We have also obtained consent to participate from each of the respondents before starting the interview. The confidentiality of information

GCK developed the questionnaire, collected the data, contributed in acquisition of data. SKS PC conceived and designed the experiments. GCK PC analyzed the

data. GCK PC wrote the manuscript. SKS critically revised the draft.

*DOI: http://dx.doi.org/10.5772/intechopen.95110*

**5. Conclusion**

**Declarations**

has been maintained.

Not applicable.

**Funding**

**Consent for publication**

**Availability of supporting data**

Not received any funding.

**Authors' contributions**

This research is based on primary data.

**Ethics approval and consent to participate**

have minimal occupational and safety training [25–29].

*Responsiveness of Occupational Health Risk and Preventive Measures Practice by the Workers… DOI: http://dx.doi.org/10.5772/intechopen.95110*

An intervention study focused on prevention of work-related skin problems assessed the occupational health and safety among wet workers. The study found significant behavior change and fewer skin problems among workers in the intervention group as compared to the control group. The intervention was successful in enhancing knowledge and changing behavior [24]. Literature suggests most workers had an essential awareness of the existence of occupational health and safety legislation, but they were unaware of their legal responsibilities. They were found to have minimal occupational and safety training [25–29].


**4. Conclusions**

To further apply an unpowered ventilator in different buildings or tunnels and quickly exhaust smoke during building and tunnel fires, in this study, we conducted a series of experiments to investigate its ventilation and smoke exhaust performance. Our conclusions are summarized as follows:

The natural ventilator constructed in this study was a swirling natural ventilator 6. This type of unpowered ventilator was also used in the smoke exhaust experiments. Therefore, we conclude that this type of ventilator is more suitable for selected flow natural ventilators, and the optimized natural ventilator is suitable for smoke exhaust from buildings or tunnels. However, in other scenes (such as factories), the optimized unpowered ventilator has not been tested, which is a future research direction for natural ventilator smoke exhaust.

**Author Contributions:** M.L.: Conceptualization, Methodology; Y.Q.: Formal analysis, Writing-Original Draft; X.W.: Investigation; W.S.: Formal analysis; Y.Z.: Writing-Reviewing and Editing; L.Y.: Supervision, Methodology, Resources. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research is funded by the Science and Technology Project of Department of Transportation of Yunnan Province under grant No. [2013]261.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.


**Generation of** *GLA***-Knockout Human Embryonic Stem Cell Lines to Model Autophagic Dysfunction and Exosome Secretion in Fabry Disease-Associated Hypertrophic Cardiomyopathy**

**Hui-Yung Song 1,2, Chian-Shiu Chien 1,2, Aliaksandr A. Yarmishyn 1,2, Shih-Jie Chou 1,2, Yi-Ping Yang 2,3,4, Mong-Lien Wang 1,2,3,4, Chien-Ying Wang 3,5, Hsin-Bang Leu 2,3,6, Wen-Chung Yu 3,6, Yuh-Lih Chang 1,3,4,7,\* and Shih-Hwa Chiou 1,2,3,8,\***

Received: 25 February 2019; Accepted: 4 April 2019; Published: 8 April 2019

**Abstract:** Fabry disease (FD) is a rare inherited disorder characterized by a wide range of systemic symptoms; it is particularly associated with cardiovascular and renal problems. Enzyme replacement therapy and pharmacological chaperone migalastat are the only approved and effective treatment strategies for FD patients. It is well documented that alpha-galactosidase A (GLA) enzyme activity deficiency causes globotriaosylceramide (Gb3) accumulation, which plays a crucial role in the etiology of FD. However, the detailed mechanisms remain unclear, and the lack of a reliable and powerful disease model is an obstacle. In this study, we created such a model by using CRISPR/Cas9-mediated editing of *GLA* gene to knockout its expression in human embryonic stem cells (hESCs). The cardiomyocytes differentiated from these hESCs (GLA-null CMs) were characterized by the accumulation of Gb3 and significant increases of cell surface area, the landmarks of FD-associated cardiomyopathy. Furthermore, we used mass spectrometry to compare the proteomes of GLA-null CMs and parental wild type CMs and found that the Rab GTPases involved in exocytotic vesicle release were significantly downregulated. This caused impairment of autophagic flux and protein turnover, resulting in an increase of reactive oxygen species and apoptosis. To summarize, we established a FD model which can be used as a promising tool to study human hypertrophic cardiomyopathy in a physiologically and pathologically relevant manner and to develop new therapies by targeting Rab GTPases signaling-related exosomal vesicles transportation.

**Keywords:** Fabry disease; human embryonic stem cells; CRISPR/Cas9 genomic editing; Mass spectrometry proteomic analysis; hypertrophic cardiomyopathy; disease model

#### **1. Introduction**

Approximately 3–5% of inherited hypertrophic cardiomyopathies result from lysosome storage disorders [1]. One of these cardiomyopathies is Fabry disease (FD), which is caused by alpha-galactosidase A (GLA) deficiency leading to accumulation of globotriaosylceramide (Gb3) in several tissues. FD is particularly manifested in renal and cardiovascular dysfunctions [2]. A number of in vivo and in vitro studies revealed that the loss of GLA results in left ventricular hypertrophy and develops into heart failure, myocardial infarction and life-threatening arrhythmias due to Gb3 deposition. The levels of Gb3 and its deacylated derivative, globotriaosylsphingosine (lyso-Gb3) in plasma and tissues are used as diagnostic biomarkers of FD, and are applied for the screening/monitoring of FD patients by liquid chromatography-tandem mass spectrometry (LC-MS/MS) [3–6]. However, the limited sample volume and variable levels of lyso-Gb3 in different matrices makes the quantitation very challenging [7]. Furthermore, the detailed mechanism of how Gb3 accumulation results in hypertrophic cardiomyopathy still needs to be elucidated. In order to develop new therapeutic strategies for FD-associated vasculopathy, it is essential to understand the underlying pathogenesis mechanisms, as well as to discover the potential prognostic biomarkers.

Previously, we generated CRISPR/Cas9-edited GLA-null human HEK293 cells; however, this cell line may not be an appropriate model with which to study pathological events occurring in cardiomyocytes [8]. The pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent cells (iPSCs), offer a great potential for modelling human diseases as they can be differentiated into the tissue affected by the pathology. Although several FD-specific iPSC lines have been obtained from patients carrying different *GLA* gene mutations, which claimed to be useful for FD cardiomyopathy research [9,10], one major limitation of such approach is the influence of variable genetic background, which can be significant even for monogenic, dominant and highly penetrant disease in FD [11,12]. Currently, CRISPR/Cas9 emerges as a powerful genome editing technique, providing the opportunity to efficiently delete genes to establish isogenic cells [13–15]. Therefore, our strategy in this study was to generate *GLA* knockout in human pluripotent stem cells by CRISPR/Cas9-mediated gene editing, and compare them with the parental cells of the same genetic background to study the mechanisms of FD-associated cardiomyopathy.

Recently, it became increasingly clear that lysosomal storage disorders have an impact on autophagic dysfunction [16]. Dysregulated ceramide metabolism can trigger cytotoxic signaling cascades, including apoptosis and necroptosis, missorting and accumulation of these sphingolipids in the membrane subdomains may destabilize lipid bilayer and cause their permeabilization [17]. Exosomes are small vesicles secreted upon fusion of multivesicular endolysosomal compartments with the plasma membrane and are derived from the intraluminal vesicles (ILVs) of those organelles. Exosomes may participate in the control of cellular homeostasis by promoting the release of intracellular harmful components, including proteins, lipids or nucleic acids. Emerging evidence from the studies of normal development, as well as multiple disease studies, is beginning to reveal a coordinated exosome–autophagy response that functions to maintain homeostasis through lysosomal degradation and release of cellular cargo [18–20]. However, little effort has been made to investigate the impact of autophagic dysfunction in FD on biogenesis and secretion of exosomes.

In the current study, we applied CRISPR/Cas9-mediated genomic editing to deplete *GLA* expression in ESC-derived cardiomyocytes to recapitulate FD cardiac hypertrophy in vitro and performed proteomic analysis by LC-MS/MS. We identified that Rab GTPase signaling-related vesicle secretion is the factor that may initiate or exacerbate the development of FD-associated cardiomyopathy. Such information will be extremely important for potential application in the prevention of and in interventions for the adverse effects of the cardiac hypertrophy in FD patients.


**6. Classification of porous ceramic**

porous ceramics such as the replica method, the sacrificial phase technique, direct foaming methods, paste extrusion and most recently developed rapid prototyping technique [13].

The fields of application and specific forms of porous ceramics are wide and varied according to their manufacturing processes [14]. Some of its useful applications are in the manufacture of filter. As these porous structures are used to filter high-pressure gas at high temperature and are used as an aid to remove the contaminants. In the field of petroleum treatment, porous ceramics are used as a substrate for catalysts in the process of filtration. They are also used in recovering hydrogen from the crude oil. Other applications are thermal insulators in filter membrane to separate metal impurities from molten metals such as steel, iron and aluminum. Today, porous ceramic structures prepared from different materials based on their application are used widely in biomedical field. For example, porous calcium phosphate materials can be used to replicate bone architecture and allow the growth of osseous tissue on an artificial substrate, thereby forming an artificial living bone structure. There porous hydroxyapa-

Porous ceramics possess a number of suitable properties, which combine the features of ceramics, and porous materials such as low density, lightweight, low thermal conductivity, low dielectric constant, thermal stability, high specific surface area, high specific strength, high permeability, high resistance to chemical attack and high wear resistance [13]. Either porous ceramics are reticulate (interconnected voids surrounded by a connection of ceramic) or foam (closed voids within a continuous ceramic matrix). Reticulated porous ceramics are usually used for molten metal, industrial hot-gas filters, catalyst supports, and diesel engine exhaust filters.

Pore size and porosity percentage are controlled by the particle size distribution of starting ceramic powders, fabrication techniques, types of binder used, concentration of binder and sintering conditions respectively [1]. Generally, the particle size of raw ceramic powder should be geometrically in the range between two to five times larger than that of pores in order to provide the desired pore size. The Porosity percentage reductions with increased making conditions such as pressure, sintering temperature and time. Furthermore, the fabrication influences such as the amount and type of additives, green densities, and sintering conditions (temperature, pressure atmosphere, etc.) significantly affect for the porous ceramics microstructures.

The general properties for porous ceramics can be designed for specific environmental application by controlling their composition and microstructure [16]. Changes in open and closed porosity, distribution of pore size and shapes of pore can have a main effect on the properties of porous ceramics. All of these microstructural features are in turn greatly affected by the processing way used to produce of the porous ceramic. For mechanical properties of porous ceramics, they are determined by their structural parameters, such as percentage of porosity, pore size, and shape. Furthermore, the solid microstructure phase of grain growth and solid phase continuity greatly affect the mechanical properties. Several important issues relating to

tite can be used to replace bone and also as a drug delivery system [15].

**4. Porous ceramic structure and properties**

4 Recent Advances in Porous Ceramics

**5. Mechanical behavior of porous ceramic**

Classification of pores is one of the basic requirements of inclusive characterization of porous ceramics (**Figure 3**). There are different classes of pores described porous ceramic in the literature,

**Figure 3.** Schematic of classification of porous ceramic [1].

but they are difficult to give a consistent general classification of porous ceramics including catalyst carriers in various chemical processes, electrolyte carriers in fuel elements, adsorbents. As well as filtration of liquids, hot gases, melted metals and alloys, membranes for separation and purification of gas and liquids etc. The purpose of these classifications is to organize pores in classes by grouping them based on their common characteristics like structure, size, shape, accessibility etc. Therefore, porous ceramics can be classified according to the different characteristic attributes such as chemical composition of initial ceramic materials, porosity percentage, physical state of these products, refractoriness correlated to service temperatures, destination and application area [1].

**9. Porous hydroxyapatite ceramic and its biomedical applications**

Hydroxyapatite (HA) porous ceramics are substitute materials for bone and teeth in repairing and regeneration applications due to their chemical and biological similarity to human hard tissue [20]. In the design of these porous ceramic for bone repairing or regeneration, it is important to control their pore structures. Pore ceramic structure can be designed using the size and morphology of the Hydroxyapatite particles that are utilized to build these porous ceramics. Porous hydroxyapatite ceramic exhibits strong joining to the bone, the pores provide a strong mechanical interlock leading to a firmer fixation of the structure. Porous hydroxyapatite is more resorbable and osteoconductive than HA dense counterpart [21]. The surface area of porous Hydroxyapatite form is greatly increased which allows more bone cells to be carried in comparison with dense hydroxyapatite. The most common techniques used to make porosity in a biomaterial are gas foaming, salt leaching, freeze-drying, phase separation and sintering depending on the material used to make the scaffold. The minimum pore size

Introductory Chapter: A Brief Introduction to Porous Ceramic

http://dx.doi.org/10.5772/intechopen.74747

7

required to regenerate mineralized bone is generally considered to be around 100 μm.

Porous ceramics have a good activity and high absorption materials. The reaction rate and conversion increase significantly for the reactive fluid that flows through the porous ceramic networks [22]. The ceramic catalyst carrier plays a major role in promoting the chemical reaction. Due to the chemical corrosion resistance and thermal shock of porous ceramics, they can be used in highly required service conditions, like the reactor in chemical engineering and the vehicles gas exhaust treatment. As well as the fine metal particles are usually supported on the heterogeneous catalyst carriers, which are generally ceramic. Catalysis becomes also progressively more important in environmental pollution control. The catalyst effectively reduced pollution from automotive and industries applications. The ceramic used must have connected porosity and the pore size can differ between 6 nm and 500 μm. Alumina, titania, zirconia silica and silicon carbide are the most popular choices for catalyst supports. These ceramic powders are formed into a variety of shapes such as cylinder bars or hollow beads or clover-leaf shaped sections. They are then sintered to their final density. Porous ceramics also can be used as carriers in the recycling of steam, oxidation of ammonia, recombination of methane, destruction of volatile organic compounds (VOCs) by incineration and decomposition of organics by photocatalysis.

Porous ceramic membranes can be used to separate water, oil, liquids, solids, dust in gas, yeast or thallus and blood cells and to clarify alcohol in the food, chemical and medical industries. In addition, these membranes act as biological reactors in the recovery of fermented fluid. During the last few decades, the ceramic membrane applications have increased because of their excellent chemical, mechanical and thermal stability, and high separation efficiency [23]. High-permeability ceramic membranes can only be obtained in an asymmetric multilayer

**10. Porous ceramics and catalyst carriers**

**11. Porous ceramics and membranes**

## **7. Ceramic foams**

Ceramic foams are porous brittle materials with closed, open-celled structures or partially interconnected porosity [17]. Ceramic foams are a special class of porous materials included of large voids with linear dimensions in the range between 10 and 5 mm. Foams are also called cellular ceramic materials because their structure can be represented by a lattice of a repeatable unit called "cell". They are fabricated from a broad kind of ceramic materials; specifically both oxide and non-oxide, which includes pure oxides, aluminosilicates and carbides that are being considered for the whole range of possible applications. These include filtration, catalysis, impact-absorbing structures, thermal insulation, performs for metal-ceramic composites, biomechanical implants, high specific strength materials and high efficiency combustion burners. The ceramic foams have been produced in a variety of materials with different shape sizes, densities and degree of interconnectivity. Foams or cellular are usually made with the density between 10 and 40% of theoretical and the pore sizes less than 1 mm. Ceramic foams can be made with a variety of microstructures with controlled properties through several versatile and simple methods, such as direct foaming, replica, sacrificial template techniques [5].


**3.1 Why institutions matter**

We can now argue that institutions matter in economic life when individuals need social expectations to solve specific problems like that of defining 'ends' or 'goods' in economy (that I am referring to as the problem of orientation), getting information about the situation that lies ahead, especially who are the exchange partners and what are the exchange rates (this may be called the problem of coordination), and lastly, the big questions as to whether there are any common interests and how to meet them, such as the wealth of a society, justice, social order, etc.

Within the framework of action-based institution theories we can use these three kinds of social problems, but also develop more precisely shaped models of social action in economy that has need for institutions in general. This also allows us to focus on the underlying problem in a more concise way by stating why and how particular aspects of the situation and of individual action become relevant. Hence, it is possible to define a wide range of social action problems that matter in the economic field by giving precise arguments about the underlying logic and the degree of the problem that has to be overcome in order to found social action and relations in the economic sphere.

If we start with the very simple assumption that individuals act in order to meet private interests, we can argue that with regard to the three logics of interdependency described above the general need for *orientation* is not that problematic, since every orientation is better than none. Because of this, simple common knowledge as well as cultural symbols or defined social standards or information by chance can help to act intentionally. In all of these cases, 'focal points' help by saying what action is to be expected. Furthermore, because of their positive effects, such patterns of orientation are stabilizing step by step and therefore create path-depending social solutions that are not problematic or further discussed. That is what Neo-Institutionalists have in mind when arguing that processes of institutionalization happen and create social expectations without anyone noticing.

If we start with complementary interests it is to argue that, in the easiest case, two or more actors only need to know what the other will do in order to act intentional. This case is described for example by Thomas Schelling as a pure coordination game of 'strangers' who

This can be seen as a starting point for an integrated approach that focuses and systemizes social situations which, in the sense of social expectations, make institutions advantageous

Therefore, I am arguing now on the basis of a theory of intentional actions that is more precise, in the sense that realistic theses can be formulated about the conditions as well as the functioning of main economic institutions in modern societies, when we do not start with the assumption of given or socially founded expectations on the macro level. Instead, I suggest starting with simple assumptions about individuals trying to act with regard to their own intentions in social fields and therefore dealing with the problem of social expectation. Hence, we consider the processes of establishing and maintaining institutions in economic fields by regarding individual intentions as well as capabilities on the one hand,

We can now argue that institutions matter in economic life when individuals need social expectations to solve specific problems like that of defining 'ends' or 'goods' in economy (that I am referring to as the problem of orientation), getting information about the situation that lies ahead, especially who are the exchange partners and what are the exchange rates (this may be called the problem of coordination), and lastly, the big questions as to whether there are any common interests and how to meet them, such as the wealth of a society,

Within the framework of action-based institution theories we can use these three kinds of social problems, but also develop more precisely shaped models of social action in economy that has need for institutions in general. This also allows us to focus on the underlying problem in a more concise way by stating why and how particular aspects of the situation and of individual action become relevant. Hence, it is possible to define a wide range of social action problems that matter in the economic field by giving precise arguments about the underlying logic and the degree of the problem that has to be overcome in order to

If we start with the very simple assumption that individuals act in order to meet private interests, we can argue that with regard to the three logics of interdependency described above the general need for *orientation* is not that problematic, since every orientation is better than none. Because of this, simple common knowledge as well as cultural symbols or defined social standards or information by chance can help to act intentionally. In all of these cases, 'focal points' help by saying what action is to be expected. Furthermore, because of their positive effects, such patterns of orientation are stabilizing step by step and therefore create path-depending social solutions that are not problematic or further discussed. That is what Neo-Institutionalists have in mind when arguing that processes of institutionalization

If we start with complementary interests it is to argue that, in the easiest case, two or more actors only need to know what the other will do in order to act intentional. This case is described for example by Thomas Schelling as a pure coordination game of 'strangers' who

for individual actors, but also looks for their intended and unintended consequences.

and by taking specific social constellations into account on the other.

found social action and relations in the economic sphere.

happen and create social expectations without anyone noticing.

**3. Social institutions in modern economy**

**3.1 Why institutions matter**

justice, social order, etc.

are to meet in New York but have not made arrangements as to where and when. Then simple common knowledge can help and can build up to institutions by used private or common knowledge; for example to meet at the most famous place in town and the usual time.

The challenge for economic sociology is to figure out situations that make social interaction or exchange useful for individuals, but cause the need for stable mutual institutions at the same time. Thus, by analyzing the structure of interests we can describe the problem and ask what sort of institution might be necessary and possible. If formal institutions guaranteed by hierarchies are to be explained, we can say that unintended by-products are to be expected caused by the conflicting interest structure between rulers and staff as well as between rulers and obedients.

But this is not the overall case when focusing on *coordination problems* – most important in modern economic life – because successful social coordination benefits from complementary interests and therefore needs only to restrict the individual's scope of action in order to gain the positive effects of specializing, labor division, or agency. Coordination is a general problem in modern societies and economies because of the socially guaranteed rights of individuals to act and the formally defined property rights (including the formal right to enter into a contract, e.g. a market or an employer-employee relationship). Ergo, we can consider the problems that come along with such social relations and look for adequate social institutions that help to stabilize them, causing intended as well as unintended social and economic effects. In this framework, the often mentioned general trust problem can now be considered more precisely either as a problem of one-spot exchange by strangers or as a long-term exchange within a group that shares social norms or as a long-term exchange within a conflict arena and therefore making opportunism and strategic action relevant. To shape typical coordination problems in the economic sphere, it is helpful to consider firstly situational aspects and add special individuals' skills (to strengthen coordination problems, it is helpful to reflect which capabilities would help but are missing, e.g. to have the right information, to have complete information, to have and reflect ends logically, and, most of all, to act rationally with regard to intentions or ends like consumer utility, profit, common interests, and so on). Coordination problems are essential in modern economic life because both market exchange as well as employer-employee relationships can be regarded as a general problem of coordination, but with a specific logic (see paragraph 3.2 and 3.3). Whereas market exchange is mostly driven by trust problems that result from incomplete information (about the others, e.g. either private consumers, firms, the state, or, above all, about the commodities), social relations within business firms are a kind of trust problem that goes along with employees acting on behalf of their employers and their employers' interests. It is not so much the exchange of goods and services that makes intra-firm relations problematic, but the wide range of conflict patterns like opportunism, agency problems, strategic action, etc. Therefore, it can be stated that such social institutions are advantageous that firstly solve the coordination problem and secondly help to frame the conflict structure. Privately-owned firms in modern economies can be viewed as an institutionalized answer to the problem of controlling and determining the actions of others. Business firms have to be explained by analyzing the incentives given in and by hierarchical structures.

Economic Sociology: Bringing Back Social Factors 89

to consider the existence of these institutions on the basis of problems of orientation,

From an institutional point of view there are three perspectives on the business firm described as a privately-owned organization producing for an anonymous market in order to make profit. The first question is: *Why* has that kind of organizational form spread so widely since the late 19th century? Secondly: *What kind of social actions* and *interdependencies*  are typical for this social setting, causing what kind of social institutions? Thirdly: How can we describe the *relationship* between *modern society* and *(large) business firms* in terms of social

The first question is well considered because of the inevitable decline of social communities (tribes, families, feudal tenures, cloisters, and guilds) as producers of scarce goods and services during the process of industrialization. Instead, centralized production in the privately-owned industry driven by pure profit-orientation increased and became the very core issue of all social sciences (Swedberg, 2003). Whereas economists and historians point out that the decline of social communities and the rise of privately-owned companies was mostly related to technical innovations, (Neo-)Marxists as well as New-Institutionalists focus on the 'transformation problem' of human labor that arises because of the two main structural elements: private property and profit-orientation. The problem is to transform the abilities of human labor into an outcome that benefits the few owners and therefore coordinates the working process and solves the agency problem by effective structures. This is the very starting point for discussing the possibility as well as the need for centralized control mechanisms by private owners within the firm as an important fact for the overall success of privately-owned firms. Furthermore it is argued that the profit-orientation drives the widening of coordination effects firstly by enlarging the business and secondly by finding more and more rational ways of coordinating a large number of skilled workers. Economists and historians showed that social coordination effects the process of establishing more complex organizational and managerial structures, as well as organizing the production on a large scale and scope (Chandler, 1962; Williamson, 1985; North, 1990).

Therefore, the formal organizational structures as well as the formation of managerial structures gained a lot of attention during the 20th century. One of the most exciting aspects discussed within sociology – especially in the sociology of work – relates to the change of *control systems.* It is stated that direct and personal forms of control lost relevance and were substituted by more technical and bureaucratic forms of control (Edwards, 1979) and lastly by new forms of self-control (Burawoy, 1979; Piore & Sabel, 1984). With this reading, sociology competes with New Economic Institutionalism that offers a strong argument for the rise of various kinds of managerial and structural forms in the 1930s in the US and in the 1950s in Europe because of information overload on the top management, which generated a need for certain kinds of institutions or for organizational change. Managers as well as hierarchies within this framework are regarded as effective mechanisms of coordination

*a. Why privately-owned and hierarchically organized (large) business firms*

coordination, and cooperation.

action and social expectations?

*b. Social expectations within firms*

established by the private owners.

**3.2.1 The large firm**

In contrast to economic theory that focuses mainly on exchange and complementary interests, sociology and political theory normally focus on *common interests* and therefore coordinated collective behavior. The classic answer to this is given by Max Weber (see paragraph 2) who argued that a means-end and legally founded order creates an organization ("Verband") that provides rational collective action in all fields. But Weber's solution is based on the assumption of a given legitimacy ("Anerkennung") and is lacking an explanation on how this can be constituted as well as on how collective action in economic fields can be organized by alternative mechanisms when legitimacy fails. Whereas sociologists take common interests seriously when discussing collective actions, they do not ask for the corresponding problems that might be caused by individual interests. This is because they argue like Weber or assume that common interests enforce collective actions themselves. One of the major insights of using a rational-choice theory is that common interests do not automatically lead to collective actions, but also need social institutions to be guaranteed. This means we need to ask when and why intentional actors are able to create social institutions that allow them to solve the various problems that go along with collective action, first of all the various kinds of free-riding, but also problems of defining ends (Offe & Wiesenthal, 1980; Wiesenthal, 1993). Because free-riding is a dominant strategy when common interests are enforced by others, such expectations need to be enforced either inside the group by social mechanisms or by establishing authority and control structures – all of which are also public goods. Economic sociology can use and broaden the concept of public goods to discuss why producer or consumer associations are so rarely to be found in modern economies or what social institutions are possible and necessary to establish and maintain such associations. An economically interesting variation of this general problem is discussed by Russell Hardin and Elinor Ostrom as 'Tragedy of Commons'. Ostrom (1990) in particular showed that the economic use of scarce common goods like water or fish can be governed within small groups and informal trust-based rules and local knowledge.


**Abstract**

Given the increased prevalence of obstructive sleep apnea (OSA) multiple treatment modalities including medical and surgical have been developed. Firstline therapy for most of the people with obstructive sleep apnea (OSA) consists of behavioral modification, including weight loss if appropriate, and positive airway pressure (PAP) therapy. Patients who fail or do not tolerate PAP therapy, treatment options include oral appliances and surgical therapy. Surgical therapies have variable efficacy and are very important tool on OSA management in selected patients. This chapter will review the current surgical approaches sleep specialists use when other treatment options fail to accomplish the valuable outcome.

**Keywords:** obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP), role of surgery, surgical treatment, follow up and monitoring


**2. Indian perspective of smart cities**

Government of India (GoI), in its' election manifesto for 2014 proposed development of 100 smart cities, which in later stage transformed to brown city from green city. In other words, GoI which earlier planning for developing 100 new cities as Smart Cities later planned to develop the existing cities into smart cities. And for this purpose, SCM and AMRUT a completely different wing under Ministry of Urban Development (MoUD) was setup, which was considered a compelling stride for encyclopedic enactment for Smart Cities (**Figures 2** and **3**). The implementation

#### **Figure 2.**

*Smart cities: Available technologies (right) and challenges (left).*

*Example of prevailing smart building technologies (Image source: https://thegibraltarmagazine.com).*

of SCM be annexed as the contingency plan to knuckle down to defiance of securing the intent of urbanization as per nationwide domestic development plan. Sectors where SCM needs to cynosure are:

The clamant materialization for gestating of Smart Cities along Indian lexicon be enunciated as adhere to:

Smart City be defined as in Indian lexicon as "A Smart City would be the one which plans judiciously to meet its aspirations and challenges in a sustainable manner while fostering principles of good governance. These are achieved in a Smart City by utilizing the enhanced power of technology, engaging with a more aware and informed citizenry and creating a more competent and capacitated set of people working within an accountable framework."

The schema for regional area augmentation has been designed by SCM and MoUD with intent to revamping fiscal development and aspect of living. The schema has basically trilateral factors [4]: a) Area – Based Development (ABD) responsible for uplifting of the regional extant inclusive of the blighted areas into advanced and planned ones; b) Green – field Projects which would develop new provinces into state-of-the-art centre so as to facilitate the exploding populace; c) Pan –city Development (PAN) which shall anticipate the appositeness of the elicited smart and intelligent elucidation to prolonging city framework.


*Supporting open minds since 2005*

Bariatric Surgery - From the Non-Surgical Approach to the Post-Surgery Individual Care http://dx.doi.org/10.5772/intechopen.87626 Edited by Nieves Saiz-Sapena and Juan Miguel Oviedo

#### Contributors

Walid El Ansari, Wahiba Elhag, Roberto Cattivelli, Anna Usubini Guerrini, Dörte Wichmann, Dietmar Stüker, Alfred Königsrainer, Rami Archid, Ulrich Schweizer, Michelle Bernadette C. Lim-Loo, Chih-Kun Huang, Valerie Chan, Kathleen Chua, Anwar Suhaimi, Brenda Saria Yuliawiratman, Veronica Mocanu, Daniel V. Timofte, Ioana Hristov, Nieves Saiz-Sapena, Juan Miguel Oviedo, Valentina Villa, Giorgia Varallo, Valentina Granese, Giada Pietrabissa, Gian Mauro Manzoni, Gianluca Castelnuovo, Enrico Molinari

#### © The Editor(s) and the Author(s) 2021

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Bariatric Surgery - From the Non-Surgical Approach to the Post-Surgery Individual Care Edited by Nieves Saiz-Sapena and Juan Miguel Oviedo p. cm. Print ISBN 978-1-83968-173-8 Online ISBN 978-1-83968-174-5 eBook (PDF) ISBN 978-1-83968-175-2


ið Þ φ�ϕ =2 þ ba

† s ð Þ0 n o2

� �

� �

e �ið Þ φ�ϕ =2

∣Ψ > for an arbitrary |Ψ>. However, for a coherent inci-

G ¼ A2 þ B2 þ 2AB cos 2ð Þ Δ , (61)

1,2|Ψ0> � <Ψ0|bx1, 2|Ψ0>2

x1 2ð Þð Þþ 0 1

4

jΨ >

Quantum Noise in Optical Amplifiers http://dx.doi.org/10.5772/intechopen.72992

nsð Þ0 p eiθ∣Ψ >, and then

: (60)

: (62)

.

�ið Þ ϕþφ =2 ,

† � �=2 and

ð Þ G � 1 , (63)

þ B2

: (59)

131

nsð Þ¼ L A2 þ B2 � �nsð Þþ 0 AB < Ψj f g basð Þ0 2

∣Ψ > and < Ψ∣ ba

† s ð Þ0 n o2

From the first term in Eq. (60), the signal gain is expressed as

< Ψ∣f g basð Þ0 2

Eq. (59) is developed as

5.3. Amplitude fluctuation

† � �=2i, respectively, as σ2

σ2

bx2 ¼ bb � bb

$$
\overline{n}\_s(L) = \overline{n}\_s(0)A^2 + B^2. \tag{54}
$$

Eq. (53) indicates that the signal field is simply amplified while preserving the phase state, with no additional field on average. On the other hand, Eq. (54) shows that the output photons consist of two components. The first term is proportional to the incident photon number, which corresponds to the amplified signal photons with a gain of

$$A^2 = \cosh^2(gL) + \left(\Delta\beta/2\mathfrak{g}\right)^2 \sinh^2(gL) \equiv \mathbb{G}.\tag{55}$$

It is noted in this expression that parameter g = {|κ|2 – (Δβ/2)2 } 1/2 is equivalent to the gain coefficient. When Δβ = 0, g is maximum and the signal gain is maximum. Therefore, it is important to satisfy the condition Δβ = 0, that is called the "phase matching condition," in implementing an OPA [9]. The second term in Eq. (54) is independent on the signal input, and represents spontaneously emitted photons. The above results, i.e., the spontaneous light does not appear in the mean amplitude while it does in the photon number, suggest that the amplitude of the spontaneous emission is completely random. However, we do not know how random it is at this stage. The photon number of the spontaneous emission is expressed from the second term in Eqs. (54) and (52c) as

$$B^2 = \left\{ 1 + \left(\Delta\beta/2g\right)^2 \right\} \sinh^2(gL) = G - 1,\tag{56}$$

where Eq. (55) is applied. This expression is equivalent to the spontaneous photon number in population-inversion-based amplifiers indicated in Eq. (29) with nsp = 1. This correspondence suggests that nondegenerate OPAs can offer the ideal noise performance achievable in EDFAs, which is shown later.

Regarding degenerate OPA, on the other hand, its mean output amplitude is calculated as

$$\overline{a}\_{\mathbf{s}}(L) = \left\{ A e^{i\left\{\theta\_0 + \left(\varphi - \phi\right)/2\right\}} + B e^{-i\left\{\theta\_0 + \left(\varphi - \phi\right)/2\right\}} \right\} |\overline{a}\_{\mathbf{s}}(0)| e^{i\left(\varphi + \phi\right)/2} \,\tag{57}$$

where θ0 is the phase of the incident signal light. The mean output amplitude does not have a simple form as in nondegenerate OPA (Eq. (53)). Under the condition where Δβ = 0 and the gain coefficient g is so large as cosh(gL) ≈ sinh(gL) ≈ e gL/2, Eq. (57) is approximated as

$$\overline{a}\_{\mathfrak{s}}(L) = \cos\left(\Delta\right)e^{\mathfrak{s}L}|\overline{a}\_{\mathfrak{s}}(0)|e^{i\{\psi+\phi\}/2},\tag{58}$$

where Δ � θ0 + (φ – ϕ)/2 is introduced. This expression indicates that the phase state of the incident signal light is not transferred to the output.

The mean photon number in degenerate OPA is calculated from Eq. (51) as

$$\mathfrak{n}\_s(L) = \left(A^2 + B^2\right)\mathfrak{n}\_s(0) + AB\left\{ <\Psi \Big| \left[\widehat{a}\_s(0)\right]^2 e^{i\left(\psi - \phi\right)/2} + \left\{\widehat{a}\_s^\dagger(0)\right\}^2 e^{-i\left(\psi - \phi\right)/2} \right] \Big| \Psi > \right\} + B^2. \tag{59}$$

Unfortunately, this equation cannot be further developed, because we cannot readily calculate < Ψ∣f g basð Þ0 2 ∣Ψ > and < Ψ∣ ba † s ð Þ0 n o2 ∣Ψ > for an arbitrary |Ψ>. However, for a coherent incident state, these quantities can be evaluated using basð Þ0 ∣Ψ >¼ ffiffiffiffiffiffiffiffiffiffiffi nsð Þ0 p eiθ∣Ψ >, and then Eq. (59) is developed as

$$
\overline{n}\_s(L) = \overline{n}\_s(0) \left\{ A^2 + B^2 + 2AB \cos \left( 2\Delta \right) \right\} + B^2. \tag{60}
$$

In this expression, the first term represents amplified signal photons, and the second term represents spontaneous emission whose mean amplitude is zero as indicated in Eq. (57).

From the first term in Eq. (60), the signal gain is expressed as

$$G = A^2 + B^2 + 2AB\cos(2\Delta),\tag{61}$$

which is dependent on the relative phase Δ = θ0 + (φ�ϕ)/2. Hence, degenerate OPA is called "phase-sensitive amplifier (PSA)." The maximum gain is obtained when Δ = 0 as

$$\mathcal{G}(\Delta = 0) = (A + B)^2. \tag{62}$$

#### 5.3. Amplitude fluctuation

5.2. Mean amplitude, photon number, and signal gain

which corresponds to the amplified signal photons with a gain of

A2 ¼ cosh2

It is noted in this expression that parameter g = {|κ|2 – (Δβ/2)2

B2 ¼ 1 þ Δβ=2g � �2 n o

from the second term in Eqs. (54) and (52c) as

gain coefficient g is so large as cosh(gL) ≈ sinh(gL) ≈ e

incident signal light is not transferred to the output.

which is shown later.

and nsð Þ¼ L < Ψ0∣ba†

130 Optical Amplifiers - A Few Different Dimensions

from Eq. (51) as

The mean amplitude and photon number at the output are evaluated by asð Þ¼ L < Ψ0∣basð Þ L ∣Ψ0 >

nsð Þ¼ L nsð Þ0 A2 þ B2

Eq. (53) indicates that the signal field is simply amplified while preserving the phase state, with no additional field on average. On the other hand, Eq. (54) shows that the output photons consist of two components. The first term is proportional to the incident photon number,

ð Þþ gL Δβ=2g � �2

coefficient. When Δβ = 0, g is maximum and the signal gain is maximum. Therefore, it is important to satisfy the condition Δβ = 0, that is called the "phase matching condition," in implementing an OPA [9]. The second term in Eq. (54) is independent on the signal input, and represents spontaneously emitted photons. The above results, i.e., the spontaneous light does not appear in the mean amplitude while it does in the photon number, suggest that the amplitude of the spontaneous emission is completely random. However, we do not know how random it is at this stage. The photon number of the spontaneous emission is expressed

sinh2

where Eq. (55) is applied. This expression is equivalent to the spontaneous photon number in population-inversion-based amplifiers indicated in Eq. (29) with nsp = 1. This correspondence suggests that nondegenerate OPAs can offer the ideal noise performance achievable in EDFAs,

Regarding degenerate OPA, on the other hand, its mean output amplitude is calculated as

where θ0 is the phase of the incident signal light. The mean output amplitude does not have a simple form as in nondegenerate OPA (Eq. (53)). Under the condition where Δβ = 0 and the

where Δ � θ0 + (φ – ϕ)/2 is introduced. This expression indicates that the phase state of the

gL∣asð Þ0 ∣e

ið Þ φþϕ =2

asð Þ¼ L Aeif g θ0þð Þ φ�ϕ =2 þ Be�if g θ0þð Þ φ�ϕ =2 n o

asð Þ¼ L cos ð Þ Δ e

s ð Þ L basð Þ L ∣Ψ0 >, respectively. For nondegenerate OPA, these are calculated

sinh2

asð Þ¼ L asð Þ0 Aeiφ, (53)

}

∣asð Þ0 ∣e

: (54)

ð Þ� gL G: (55)

ð Þ¼ gL G � 1, (56)

ið Þ φþϕ =2

, (58)

gL/2, Eq. (57) is approximated as

, (57)

1/2 is equivalent to the gain

Next, we evaluate the amplitude noise in OPAs. For the evaluation, the light amplitude is decomposed into two quadratures and the variance of each quadrature is calculated, as in Section 4.3. In case of OPAs, the output field operator is phase-shifted by (φ + ϕ)/2, as indicated by Eq. (51). Accordingly, we introduce a phase-shifted field operator defined as bb � base �ið Þ ϕþφ =2 , and evaluate the variances of the real and imaginary components of bb, i.e., bx1 ¼ bb þ bb † � �=2 and

$$
\widehat{\mathbf{x}}\_2 = \left(\widehat{\boldsymbol{b}} - \widehat{\boldsymbol{b}}^\dagger\right) / 2\mathbf{i}, \text{ respectively, as } \sigma\_{\ge 1(2)}^2 = \sphericalangle \Psi\_0 |\widehat{\boldsymbol{\chi}}\_{1,2}^2| \, |\Psi\_0 > -\sphericalangle \Psi\_0 |\widehat{\boldsymbol{\chi}}\_{1,2}| \, |\Psi\_0 > 2\Delta
$$

The calculation result for nondegenerate OPA is expressed as

$$
\sigma\_{\mathbf{x}1(2)}^2(L) = A^2 \sigma\_{\mathbf{x}1(2)}^2(0) + \frac{1}{4}B^2 = A^2 \sigma\_{\mathbf{x}1(2)}^2(0) + \frac{1}{4}(G-1),\tag{63}
$$

where Eqs. (55) and (56) are applied. The first term represents noise amplified from the incident light, and the second term represents additional noise superimposed via OPA. Note that Eq. (63) is equivalent to the amplitude variance of population-inversion-based amplifiers shown by Eq. (35) with nsp = 1, suggesting that the ideal noise performance achievable in EDFAs can be obtained in OPA. Similar to Eq. (35), Eq. (63) is rewritten for a coherent incident state as

$$
\sigma\_{\ge 1(2)}^2(L) = \frac{1}{4} + \frac{1}{2}(G - 1). \tag{64}
$$

The first term is the inherent quantum noise of a coherent state, and the second term represents noise superimposed via OPA in a classical picture. The sum of the second terms of the two quadratures equals the photon number of spontaneous emission light indicated in Eq. (56). This consideration supports the classical noise treatment, described in Section 2, where spontaneous emission with random phase is superimposed onto signal light at the amplifier output.

For degenerate OPA, on the other hand, the amplitude variances are calculated as

$$
\sigma\_{\mathbf{x1}}^2(L) = (A+B)^2 \sigma\_{\mathbf{x1}}^2(0) = G\_0 \sigma\_{\mathbf{x1}}^2(0),\tag{65a}
$$

$$
\sigma\_{x2}^2(L) = \left(A - B\right)^2 \sigma\_{x2}^2(0),
\tag{65b}
$$

where Eqs. (55) and (56) are applied. Recalling that the mean photon number of the amplified signal is Gnsð Þ0 and that of spontaneous emission light is (G – 1), as indicated by Eqs. (54)–(56), each term in Eq. (68) can be interpreted as follows. The first term is equivalent to 2 � (signal light intensity) � (spontaneous light intensity), which corresponds to the signal-spontaneous beat

spontaneous-spontaneous beat noise. The third and fourth terms are equal to the mean photon numbers of the amplified signal and of spontaneous emission, respectively, and correspond to the optical shot noises of the amplified signal light and the spontaneous emission, respectively. Next, we consider degenerate OPA. As indicated by Eq. (59), properties of the photon number in degenerate OPA are hard to evaluate for an arbitrary initial state. Thus, we assume a coherent incident state here. From Eq. (51), the average of the square of the photon-number

> � 2

þ 4ð Þ AB 2 þ 4 A2 þ B2 � �ABcos 2ð Þ Δ n onsð Þþ 0 2ð Þ AB 2

þ 4ð Þ AB 2 þ 4 A2 þ B2 � �ABcos 2ð Þ Δ n onsð Þþ 0 2ð Þ AB 2

,

þ 4ð Þ AB 2 þ 4 A2 þ B2 � �AB cos 2ð Þ Δ n onsð Þþ 0 2ð Þ AB 2

where Eq. (61) is applied. This expression cannot be decomposed and interpreted as that of nondegenerate OPA indicated by Eq. (68), which could be because the amplitude distribution

, which corresponds to the

Quantum Noise in Optical Amplifiers http://dx.doi.org/10.5772/intechopen.72992 133

, (68)

(69)

noise. The second term is equivalent to (spontaneous light intensity)2

Figure 3. Constellation diagram of amplified light in a phase-synchronized degenerate OPA.

operator for the initial state |Ψ0>=|α>s ⊗ |0>i is calculated as

s ð Þ L ∣Ψ0 >¼ ½A2 þ B2 þ 2ABcos 2ð Þ Δ nsð Þþ 0 B2

þ A2 þ B2 � �2

Subsequently, the photon-number variance at the output is

¼ G2 þ 4ð Þ AB 2 sin 2ð Þ 2Δ

n onsð Þþ 0 2ð Þ AB 2

is not simply isotropic in two quadratures, unlike nondegenerate OPA.

¼< Ψ0∣bnsð Þ L ∣Ψ0>2 þ A2 þ B2 � �2

nðÞ ¼ L A2 þ B2 � �2

< Ψ0∣nb 2

σ2

where G0 � G(Δ = 0) is the phase-synchronized gain introduced in Eq. (62). The results show that the output variances are unequal in the two quadratures, such that σx1 2 is enhanced while σx2 2 is depressed. Since bx1 and bx2 are the real and imaginary parts of the phase-shifted operator, respectively, this result suggests that amplitude noise along the axis of a phase of (φ + ϕ)/2 is enhanced and that along the orthogonal axis is depressed, in the complex amplitude space. It is noted in Eq. (65a) that it only has fluctuations amplified from incident light with no additional fluctuation, unlike population-inversion-based amplifiers (Eq. (35)) and nondegenerate OPA (Eq. (63)). This result suggests that even the noise-enhanced quadrature bx1 is expected to have lower noise than these amplifiers. Regarding the imaginary part, Eq. (65b) for high-gain conditions, where cosh(gL) ≈ sinh(gL) ≈ e gL/2 and then A ≈ B, is rewritten as σx1 2 ≈ 0. This consideration indicates that the amplitude noise along the phase axis orthogonal to the signal output phase approaches zero as the signal gain increases. The abovementioned characteristics of amplitude fluctuation in degenerate OPA can be illustrated in the complex amplitude space as shown in Figure 3.

#### 5.4. Photon-number fluctuation and noise figure

Next, we discusses photon-number fluctuations in OPAs, which are evaluated through the photon-number variance as σn 2 = <Ψ0|bn 2 |Ψ0> � <Ψ0|bn|Ψ0>2 . Using Eq. (51), the average of the square of the photon-number operator for nondegenerate OPA is calculated as

$$<\Psi\_0 |\hat{n}\_s^2(L)|\Psi\_0> = <\Psi\_0 |\left\{\hat{a}\_s^\dagger(L)\hat{a}\_s(L)\right\}^2 |\Psi\_0> = <\Psi\_0 |\hat{n}\_s(L)|\Psi\_0>^2 + \left(A^2 + B^2\right)A^2\overline{n}\_s(0) + \left(AB\right)^2. \tag{66}$$

Subsequently, the photon-number variance is obtained as

$$\begin{split} \sigma\_{\mathbf{n}}^{2}(L) &= \left(A^{2} + B^{2}\right) A^{2} \overline{n}\_{s}(0) + \left(AB\right)^{2} = \left(2G - 1\right) G \overline{n}\_{s}(0) + G(G - 1) \\ &= 2\left(G - 1\right) G \overline{n}\_{s}(0) + \left(G - 1\right)^{2} + G \overline{n}\_{s}(0) + G(G - 1) . \end{split} \tag{67}$$

Figure 3. Constellation diagram of amplified light in a phase-synchronized degenerate OPA.

σ2

132 Optical Amplifiers - A Few Different Dimensions

σ2

Eq. (65b) for high-gain conditions, where cosh(gL) ≈ sinh(gL) ≈ e

2 = <Ψ0|bn

2

the square of the photon-number operator for nondegenerate OPA is calculated as

the complex amplitude space as shown in Figure 3.

5.4. Photon-number fluctuation and noise figure

† s ð Þ L basð Þ L n o2

Subsequently, the photon-number variance is obtained as

nð Þ¼ L A2 þ B2 � �A2

photon-number variance as σn

s ð Þ L ∣Ψ0 >¼< Ψ0∣ ba

σ2

σx2

as σx1

< Ψ0∣nb2

x1 2ð Þð Þ¼ L 1

emission with random phase is superimposed onto signal light at the amplifier output.

For degenerate OPA, on the other hand, the amplitude variances are calculated as

x1ð Þ¼ L ð Þ A þ B 2

σ2

that the output variances are unequal in the two quadratures, such that σx1

The first term is the inherent quantum noise of a coherent state, and the second term represents noise superimposed via OPA in a classical picture. The sum of the second terms of the two quadratures equals the photon number of spontaneous emission light indicated in Eq. (56). This consideration supports the classical noise treatment, described in Section 2, where spontaneous

σ2

where G0 � G(Δ = 0) is the phase-synchronized gain introduced in Eq. (62). The results show

2 is depressed. Since bx1 and bx2 are the real and imaginary parts of the phase-shifted operator, respectively, this result suggests that amplitude noise along the axis of a phase of (φ + ϕ)/2 is enhanced and that along the orthogonal axis is depressed, in the complex amplitude space. It is noted in Eq. (65a) that it only has fluctuations amplified from incident light with no additional fluctuation, unlike population-inversion-based amplifiers (Eq. (35)) and nondegenerate OPA (Eq. (63)). This result suggests that even the noise-enhanced quadrature bx1 is expected to have lower noise than these amplifiers. Regarding the imaginary part,

2 ≈ 0. This consideration indicates that the amplitude noise along the phase axis orthogonal to the signal output phase approaches zero as the signal gain increases. The abovementioned characteristics of amplitude fluctuation in degenerate OPA can be illustrated in

Next, we discusses photon-number fluctuations in OPAs, which are evaluated through the

¼ 2ð Þ G � 1 Gnsð Þþ 0 ð Þ G � 1 2 þ Gnsð Þþ 0 G Gð Þ � 1 ,

|Ψ0> � <Ψ0|bn|Ψ0>2

∣Ψ0 >¼< Ψ0∣bnsð Þ L ∣Ψ0>2 þ A2 þ B2 � �A2

nsð Þþ 0 ð Þ AB 2 ¼ ð Þ 2G � 1 Gnsð Þþ 0 G Gð Þ � 1

x2ð Þ¼ L ð Þ A � B 2

x1ð Þ¼ 0 G0σ2

σ2

ð Þ G � 1 : (64)

x1ð Þ0 , (65a)

gL/2 and then A ≈ B, is rewritten

. Using Eq. (51), the average of

nsð Þþ 0 ð Þ AB 2

: (66)

(67)

2 is enhanced while

x2ð Þ0 , (65b)

where Eqs. (55) and (56) are applied. Recalling that the mean photon number of the amplified signal is Gnsð Þ0 and that of spontaneous emission light is (G – 1), as indicated by Eqs. (54)–(56), each term in Eq. (68) can be interpreted as follows. The first term is equivalent to 2 � (signal light intensity) � (spontaneous light intensity), which corresponds to the signal-spontaneous beat noise. The second term is equivalent to (spontaneous light intensity)2 , which corresponds to the spontaneous-spontaneous beat noise. The third and fourth terms are equal to the mean photon numbers of the amplified signal and of spontaneous emission, respectively, and correspond to the optical shot noises of the amplified signal light and the spontaneous emission, respectively.

Next, we consider degenerate OPA. As indicated by Eq. (59), properties of the photon number in degenerate OPA are hard to evaluate for an arbitrary initial state. Thus, we assume a coherent incident state here. From Eq. (51), the average of the square of the photon-number operator for the initial state |Ψ0>=|α>s ⊗ |0>i is calculated as

$$<\Psi\_0 \hat{\mu}\_s^2(L) | \Psi\_0 > -[A^2 + B^2 + 2AB\cos(2\Delta)\overline{n}\_s(0) + B^2]^2$$

$$+ \left\{ \left(A^2 + B^2\right)^2 + 4(AB)^2 + 4\left(A^2 + B^2\right)AB\cos(2\Delta) \right\} \overline{n}\_s(0) + 2(AB)^2$$

$$= <\Psi\_0 |\hat{n}\_s(L)| \Psi\_0 >^2 + \left\{ \left(A^2 + B^2\right)^2 + 4(AB)^2 + 4\left(A^2 + B^2\right)AB\cos(2\Delta) \right\} \overline{n}\_s(0) + 2(AB)^2,\tag{68}$$

Subsequently, the photon-number variance at the output is

$$\begin{aligned} \sigma\_n^2(L) &= \left\{ \left(A^2 + B^2\right)^2 + 4(AB)^2 + 4\left(A^2 + B^2\right)AB\cos\left(2\Delta\right) \right\} \overline{n}\_s(0) + 2(AB)^2\\ &= \left\{ G^2 + 4(AB)^2 \sin^2(2\Delta) \right\} \overline{n}\_s(0) + 2(AB)^2, \end{aligned} \tag{69}$$

where Eq. (61) is applied. This expression cannot be decomposed and interpreted as that of nondegenerate OPA indicated by Eq. (68), which could be because the amplitude distribution is not simply isotropic in two quadratures, unlike nondegenerate OPA.

The noise figure can be evaluated from the results obtained above. For nondegenerate OPA, it is obtained as

$$\text{NF} = \frac{(\text{SNR})\_{\text{in}}}{(\text{SNR})\_{\text{out}}} = \overline{n}\_s(0) \frac{2(G-1)G\overline{n}\_s(0)}{\left\{G\overline{n}\_s(0)\right\}^2} = 2\frac{G-1}{G} \,. \tag{70}$$

where only the signal-spontaneous beat noise is considered for the output SNR, according to the definition on the noise figure. This noise figure equals that of ideal population-inversion– based amplifiers indicated by Eq. (44) with nsp = 1. For the degenerate case, on the other hand, it is expressed as

$$\text{NF} = 1 + 4 \frac{\left(AB\right)^2}{G} \sin^2(2\Lambda). \tag{71}$$

[3] Yariv A. Quantum Electronics. 3rd ed. USA: Wiley; 1989. 676 p

New York: Cambridge; 2008. 366 p

ics. 2002;8:506-520

[4] Loudon R. The Quantum Theory of Light. 3rd ed. New York: Oxford; 2000. 438 p

saturated conditions. IEEE Photonics Technology Letters. 1992;4:1261-1264

3.1 dB noise figure. IEEE Photonics Technology Letters. 1992;4:1345-1347

[11] Walls D, Milburn G. Quantum Optics. 2nd ed. Berlin: Springer; 2008. 425 p

lower than 3 dB quantum limit. Electronics Letters. 2000;36:63-64

sensitive parametric amplifier. Optics Express. 2010;18:14820-14835

[5] Inoue K. Quantum mechanical treatment of optical amplifiers based on population inversion. IEEE Journal of Quantum Electronics. 2014;50:563-567. DOI: 10.1109/JQE.2014.2325906

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[6] Smart RG, Zyskind JL, Sulhoff JW, DiGiovanni DJ. An investigation of the noise figure and conversion efficiency of 0.98 μm pumped erbium-doped fiber amplifiers under

[7] Laming RI, Zechael MN, Payne DN. Erbium-doped fiber amplifier with 54 dB gain and

[8] Marhic M. Fiber Optical Parametric Amplifiers, Oscillators and Related Devices. 1st ed.

[9] Hansryd J, Andrekson PA, Westlund M, Li J, Hedekvist P. Fiber-based optical parametric amplifiers and their applications. IEEE Journal of Selected Topics in Quantum Electron-

[10] Inoue K. Quantum noise in parametric amplification under phase-mismatched conditions. Optics Communication. 2016;366:71-76. DOI: 10.1016/j.optcom.2015.12.034

[12] Imajuku W, Takada A, Yamabayashi Y. Inline coherent optical amplifier with noise figure

[13] Tong Z, Bogris A, Lundström C, McKinstrie CJ, Vasilyev M, Karosson M, Andrekson A. Modeling and measurement of the noise figure of a cascaded non-degenerate phase-

For Δ = 0, NF = 1 (0 dB), suggesting no SNR degradation in phase-synchronized degenerate OPA. In fact, a noise figure of less than 3 dB in a phase-sensitive amplifier has been experimentally demonstrated [12, 13].

#### 6. Conclusion

This chapter describes quantum noise of optical amplifiers. Full quantum mechanical treatment based on the Heisenberg equation for physical quantity operators was presented, by which quantum properties of optical amplifiers were derived from first principles. The obtained results are consistent with a conventional classical treatment, except for the inherent quantum noise or the zero-point fluctuation, providing the theoretical base to the conventional phenomenological treatment.

#### Author details

Kyo Inoue

Address all correspondence to<EMAIL_ADDRESS>
Osaka University, Osaka, Japan

#### References

[3] Yariv A. Quantum Electronics. 3rd ed. USA: Wiley; 1989. 676 p

The noise figure can be evaluated from the results obtained above. For nondegenerate OPA, it

where only the signal-spontaneous beat noise is considered for the output SNR, according to the definition on the noise figure. This noise figure equals that of ideal population-inversion– based amplifiers indicated by Eq. (44) with nsp = 1. For the degenerate case, on the other hand,

> ð Þ AB 2 G sin 2

For Δ = 0, NF = 1 (0 dB), suggesting no SNR degradation in phase-synchronized degenerate OPA. In fact, a noise figure of less than 3 dB in a phase-sensitive amplifier has been experi-

This chapter describes quantum noise of optical amplifiers. Full quantum mechanical treatment based on the Heisenberg equation for physical quantity operators was presented, by which quantum properties of optical amplifiers were derived from first principles. The obtained results are consistent with a conventional classical treatment, except for the inherent quantum noise or the zero-point fluctuation, providing the theoretical base to the conventional phenomenological

[1] Yamamoto Y, Inoue K. Noise in amplifiers. Journal of Lightwave Technology. 2003;21:

[2] Olsson N. Lightwave system with optical amplifiers. Journal of Lightwave Technology.

NF ¼ 1 þ 4

¼ nsð Þ0 2ð Þ G � 1 Gnsð Þ0

f g Gnsð Þ0 2 ¼ 2

G � 1

G : (70)

ð Þ 2Δ : (71)

NF ¼ ð Þ SNR in ð Þ SNR out

Address all correspondence to<EMAIL_ADDRESS>
2895-2915. DOI: 10.1109/JLT.2003.816887

is obtained as

it is expressed as

6. Conclusion

treatment.

Kyo Inoue

References

Author details

Osaka University, Osaka, Japan

1989;7:1071-1082

mentally demonstrated [12, 13].

134 Optical Amplifiers - A Few Different Dimensions

## *Edited by Pankaj Kumar Choudhury*

Optical amplifiers are indispensable in long-haul communication systems operating in a relatively broad range of electromagnetic spectra. Various forms of optical amplifiers and their advancements have been extensively discussed in the literature emphasizing the relative merits and demerits of different types of configurations and/or designs and also usefulness in specific applications. The book—*Optical Amplifiers: A Few Different Dimensions*—aims at reporting developments in these devices in the recent years. The contributed chapters in this book encompass both theoretical and experimental results covering various aspects in the relevant research directions. This somehow makes the volume useful to both experts and novice researchers. Finally, the expectation remains of the contents to be of some merit for the R&D scientists working in universities and research institutions.

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Optical Amplifiers - A Few Different Dimensions

Optical Amplifiers

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*Edited by Pankaj Kumar Choudhury*


*5.1. Technocratic Disposition*

Technocracy has its advantages, especially in conflict-a ffected environments (Mac Ginty 2018). However, liberal peacebuilding has been criticised for being increasingly technocratic and professionalised, which poses barriers to local ownership and participation. Kurtz and Meyer (2018) argue that technocratic understandings of conflict prevention are now widespread, based on positivist conflict forecasting and toolbox approaches to "what works", delivered with a heavy dose of "wishful thinking" about warning–response dynamics. They call for greater focus on the "art" of conflict prevention, paying closer attention to the informal, individual and political dimensions of the endeavour. Religious peacebuilding scholars have also underlined the creativity and discernment needed for sustainable peacebuilding, which technocracy and formulaic approaches can stifle. As Lederach (2001, p. 203) notes, "Authentic reconciliation will never be packaged and delivered at drive-through windows".


*Edited by Maria Maślińska*

Epithelial tissue does not spring to mind as an obvious source of autoimmune phenomena. Yet, genetic predisposition and influence of various environmental and epigenetic factors may lead to epithelium becoming a springboard for the development of autoimmune diseases, such as Sjögren's syndrome, primary biliary cholangitis, autoimmune pancreatitis, or IgG4-related diseases. This book is intended as an introduction to the problem of "autoimmune epithelitis" and diseases closely related to the immune disturbances of the epithelium, with special emphasis on those affecting exocrine glands. Both theoretical and practical knowledge, presented by authors from a wide range of medical specialties, should be of help for medical professionals who have to deal with this difficult problem in their daily practice.

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