Preface

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), are stem cells with self-renewal and multilineage differentiation potential. For decades, we and other investigators in the field have been devoted to verifying the balance of pluripotency and early germ layer specialization of the mesoderm, endoderm, and ectoderm. State-of-the-art literature has put forward the feasibility of hPSCs for the ex vivo, large-scale preparation of stem cells and concomitant functional cells, including hematopoietic stem cells (HSCs), neural stem cells (NSCs), mesenchymal stem/stromal cells (MSCs), and immune cells (e.g., natural killer cells, T cells, megakaryocytes). Meanwhile, numerous studies have indicated the involvement of hPSCs in disease remodeling and drug screening based on diverse preclinical and clinical practices.

In this book, we mainly focus on the definition and the latest updates of hPSCs in regenerative medicine and cell preparation. For instance, MSCs derived from hPSCs reveal preferable bidirectional immunomodulation and long-term in vitro expansion over diverse counterparts from adult tissues such as adipose tissue (AD-MSCs), bone marrow (BM-MSCs), and dental pulp (DPSCs). Overall, the book highlights the feasibility of hPSCs-based cytotherapy for potential clinical applications in the future, including further development of disease remodeling and drug screening.

> **Leisheng Zhang** The Fourth People's Hospital of Jinan, Jinan, China

The Teaching Hospital of Shandong First Medical University, Shandong Province, China

> Gansu Provincial Hospital, Lanzhou, China

Section 1


**3. Case Study**

For the case study, a detailed building model was implemented in TRNSYS using Type 56. The model was composed of a single thermal zone and the envelope characteristics were extrapolated by the Tabula Project [38] for detached houses. The building was north-facing, while all the walls faced outwards and the floor was placed on the ground (considered at a constant temperature of 15 ◦C). Table 1 reports the main geometrical and thermal properties of the building that was considered (a single family house), which were extrapolated by UNI-TR 11552:2014 [39].

The structure was characterized by high levels of thermal insulation and double-glazed windows, which were air-filled, were selected (g-value of 0.7). An air change per hour (ACH) equal to 0.2 h−1 was selected. Internal gains included occupancy and artificial lighting [40]. The former was 120 W per person (occupancy density of 24 m2 per person), while an artificial light density of 5 W m−2 was considered (artificial light turns on if total horizontal radiation is less than 120 W m−2 and turns off when the value exceeds 200 W m−2). The building was located in Rome, Italy (41◦55' N, 12◦31' E), and a Meteonorm [41] weather file was used as a typical meteorological year.

In this work, the cooling season was chosen for the MPC test. Analogous results, however, could have been obtained for the heating season. As mentioned in Section 2, no specific HVAC system was modeled; instead, an ideal cooling control was used in Type 56 to extrapolate the training data [14]. In this way, the MPC control actions were applied as convective heat gains to the air nodes (positive for heating and negative for cooling). An indoor air temperature range of 25–27 ◦C was chosen as the comfort condition (i.e., *T*min and *T*max in Equation (10)) and a maximum cooling load power of 7 kW was fixed (i.e., *Q*max in Equation (11)) [42]. Since the cooling power was directly applied to the air-zone, the ideal HVAC can be compared to a traditional heat pump split system. Assuming an average COP of 2.5, the thermal energy requirement can be converted into electricity consumption, and the penalty signal can be obtained consequently (Equation (1)).

For the reference case, a fixed set-point of 26 ◦C was simulated in order to provide a comparison between the building as controlled with the MPC and without the MPC.


**1. Introduction**

Nowadays the majority of water bodies are with some degree of affectation, in Mexico City one of the main aquatic ecosystems are Xochimilco channels located in the political delegation of the same name, this zone have different appointments including that of Natural and Cultural Heritage of Humanity in 1987 by UNESCO, it was recognized as Protected Natural Area in 1992, also, is considered an ecological conservation area, it is part of the RAMSAR wetlands of global importance, and is cataloged as a GIAHS site [1].

Previously, Lake Xochimilco received water from various rivers and springs, which was mainly used for crop irrigation; besides being the habitat of native and migratory birds [2]; nevertheless, nowadays it is threatened by several problems, mainly by overexploitation of water and contamination by use of agrochemicals [3, 4].

Also, pollutant sources have been observed such as clandestine discharges of sewage from human settlements, and the deposit of solid waste [5]. Since the growth of the urban spot, there have been changes in the productive activities causing diverse problems in the area such as the excessive growth of introduced aquatic vegetation like water lilies. Water control structures have been affected in the area and it has been observed a decrease in the extension of the main and secondary channels. This has caused that in places with little or no movement of water, there is an increase in eutrophication levels and flooding during the rainy season [6].

Due to the above, the aquatic communities have been affected, one of these communities are the microalgae which, by having short life cycles, present changes in its structure and dynamics in short period of time. Also, microalgae have a great importance for Xochimilco channels, despite their small size and being unnoticed by most people, because they provide important environmental services, such as: CO2 capture, oxygen liberation from photosynthesis, natural cleaning of the water of the channels (deseutrophication), in addition to reduce the concentration of heavy metals, which are harmful to the ecosystem [7–11].

On the other hand, microalgae serve as food for other species present in water bodies, such as copepods, crustaceans, small fish, and some amphibians in juvenile stages, helping to the conservation of biodiversity. Also, can be used as biological indicators to monitor water quality [4].

Considering the above, the aim of this investigation was to know the role of microalgae in the purification of water from a Wastewater Treatment Plant, under field and laboratory conditions.


*4.2.4 mTOR*

*Type 2 Diabetes - From Pathophysiology to Modern Management*

(FOXO1)-insulin transcriptional activity [98].

*4.2.2 PPARγ*

protection from high-fat-induced obesity and insulin resistance [92–94], and slight overexpression of SIRT1 has a protective role from high-fat induced glucose intolerance [95–97]. If SIRT1 is inhibited then insulin promoter activity is suppressed, insulin regulatory genes such as v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) and NK6 homeodomain 1 (NKX6.1) mRNA expressions are down regulated leading to decreased insulin secretion. On the contrary, activation or overexpression of SIRT1 antagonizes reduced insulin transcriptional activity by exerting negative effect on pancreatic and duodenal homeobox 1 (PDX1) stimulated insulin promoter activity and also abolishes forkhead box O1 protein

PPAR-γ regulates the major β cell genes involved in glucose sensing, insulin secretion and insulin gene transcription and protects from glucose, lipid, cytokine and islet amyloid polypeptide (lAPP)-induced stress pathways [99]. PPAR-γ is a member of nuclear hormone receptor superfamily of ligand-activated transcription factors and TZDs are oral agents that are high-affinity activators of PPAR-γ [100]. PPARγ ablation protects mice from high fat diet induced insulin resistance [101] and isolated islets from these mice show blunted TZD response towards GSIS [102]. Mice with PPAR-γ ablated pancreas show glucose intolerance at baseline with downregulated Pdx-1 and GLUT2 expression in their isolated islets [103]. Chronic high glucose can decrease PPAR-γ mRNA levels in mouse islets [104]. PPAR-γ is upregulated after 60% pancreatectomy procedure in rats changing to pro differentiation state from proliferative state [105]. Promoters of GLUT2 and glucokinase have functional PPREs that bind PPAR-γ/RXRα heterodimer, and lead to transcriptional upregulation of these genes in β cell [106, 107]. The expres-

sion of these genes is impaired in diabetic rodent models [108, 109].

nitric oxide synthase and cyclooxygenase-2 expression [116].

PPARγ agonists modulate IAPP-induced ER stress [110]. The islet-specific KO of the ATP-binding membrane cassette transporter protein A1 (ABCA1) and PPAR-γ KO model both show increased intra-islet triglyceride accumulation and lowered GSIS [101, 111]. Rosiglitazone restores GSIS and decreases apoptosis in isolated human lipotoxic islets with a reduction in intra-islet triglyceride accumulation and reduced inducible nitric oxide synthase (iNOS) expression [112, 113]. PPAR-γ agonists also inhibit cytokine-induced activation of JNK in insulinoma cell lines [114]. PPAR-γ agonists have been shown to increase AKT phosphorylation in the setting of both IAPP-and lipid-inducted toxicity. These effects were blocked by PI3 kinase inhibitors and associated with increased levels of insulin receptor substrate 2

Activation of PPAR-γ inhibits IL-1β and IFN-γ stimulated nuclear translocation of p65 subunit of NF-ΚB and DNA binding activity leading to reduced inducible

PPAR-γ activation also increases intracellular calcium mobilization, insulin secretion, and β-cell gene expression through GPR40 and GLUT2 gene upregulation [117]. Thus PPAR-γ agonists not only improve insulin sensitivity in the target

Wnt signaling stimulates β-cell proliferation, specifically Wnt3a promotes expression of Pitx2, a direct target of Wnt signaling, and Cyclin D2, an essential regulator of cell cycle progression [118]. Single nucleotide polymorphisms (SNPs) in TCF7L2 are linked to etiology of T2D [119]. Expression of three Tcf genes

**10**

*4.2.3 Wnt*

(IRS2) proteins [115].

tissues, but also act within the β-cells.

Rapamycin, an mTORC1 complex inhibitor, reduces the number and proliferation of pancreatic and endocrine progenitors. Mice lacking mTOR in pancreatic progenitors suffer from hyperglycemia in neonates, hypoinsulinemia and pancreatic agenesis/hypoplasia with pancreas rudiments containing ductal structures lacking differentiated acinar and endocrine cells [123].

AMP-activated protein kinase (AMPK) is a controller of β-cell function. Inhibition of AMPK in β-cells by high glucose inversely correlates with activation of the mammalian Target of Rapamycin (mTOR) pathway. Glucose and amino acid sensing ability of AMPK is important in regulation of insulin secretion [124]. Rapamycin also induces fulminant diabetes by increasing insulin resistance and reducing-cell function and mass [125].

Obesity induced by excess nutrient intake leads to the upregulation of mTORC1/ S6K1 signaling in insulin-sensitive tissues, including β-cells [126–128]. mTORC1 activation play an initial role in adaptation to nutrient excess and obesity, but chronic and persistent hyperactivation could lead to development of insulin resistance by a negative feedback loop on IRS signaling [129].


**3. Conclusion**

accredited UCB banks, offering the possibility to develop an off-the-shelf therapy. Which degree of matching should be used will need further evaluation in clinical studies, especially as HLA matching is less stringent when considering UCB; trials using UCB Treg cells already suggested that it is possible to use a 4/6 match for UCB Treg cells when considering a thirdparty therapy. Furthermore, it is possible to purify Treg cells with high purity in one single step as opposite to a two-step process when isolating PB Treg cells [19]. CB Treg cells comprise

cells have a higher capacity to maintain Foxp3 expression, and a better suppressive capacity and stability after expansion [20]. UCB Treg cells may have a survival advantage over PB Treg cells as they have been shown to be more resistant to apoptosis than PB Treg cells [21]. Finally, we and others have demonstrated Treg cells from UCB to be able to inhibit the function of effector cells [19, 22, 23], while other groups have reported UCB Treg cells to have low suppressive capacity [24, 25]. The required cell dose for clinical use is crucial and dictates the

In any case, whatever the cell source considered, only very few cells can be isolated from UCB or PB; therefore, most groups have focused on developing strategy to expand UCB Treg cells to enable cell therapy [26–28]. The majority of expansion protocols seek to expand Treg cells and maintain their natural Treg (nTreg) cell phenotype. Multiple studies have reported expanding nTreg cells from both PB and UCB [14, 26]. Recently, conditions to expand Treg cells have become increasingly well defined and translated into GMP compliant protocols. The majority of groups (see **Table 1**) use anti-CD3 antibody attached to beads in combination with anti-CD28 for costimulation and supplemented with IL-2 ranging from 300 to 1000 IU/ml. When expanding from PB Treg cells, rapamycin is often added to the expansion cultures, sometimes in combination with retinoic acid both to prevent the outgrowth of effector T cells and to promote Treg cell expansion, especially in the case of multiple restimulations [29]. With UCB Treg cells, it is noticeable that rapamycin seems not so vital. Brunstein et al. used beads or an engineered cell line in order to expand UCB Treg cells [26, 27]. This recently published study used anti-CD3 antibody-loaded K562 cells modified to express the high-affinity Fc receptor CD64 and the costimulatory ligand CD86 [27]. Using this culture condition, expansion

Following expansion, Treg cells should as much as possible retain their nTreg cell phenotype

however, FOXP3 is also expressed on activated effector T cells and so in itself does not distinguish between them. However, FOXP3 expression should be high and sustained. In addition, Helios expression has been associated with natural Tregs, and its presence in expanded cells is also an additional indication that the cells have retained an nTreg phenotype. Expanded cells should be able to suppress the function of effector T cells in vitro. In addition, stability of the FOXP3 expression should also be tested. The methylation state of the FOXP3 locus is indicative of recent chromosomal remodelling and thus distinguishes between FOXP3 expression being induced over constitutive expression in Treg cells [30]. The study of Treg cell

CD62LlowCCR7+

practicality of the cell source considered and post-isolation manipulation if required.

in contrast to the adult PB Treg cells than

). FOXP3+ expression would seem vital;

). As a consequence, UCB Treg

almost entirely of a naïve T-cell phenotype CD45RA+

of up to 10,000 fold of UCB Treg cells was achieved.

FOXP3+

CD127lowCD25+

(CD3+

CD4+

have a central memory phenotype (CD62LhighCCR7highCD45RO+

174 Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

Immunotherapy has been a promising option in order to improve the outcome of HSCT. UCB‐ derived immunotherapies are very promising, and future studies will help us understanding their potential better. UCB Treg cells could become an immunotherapy of choice for treating GvHD. In addition, one should also consider the use of UCB plasma that already contains proteins with the capacity to modulate the immune response in particular inflammation to treat skin GvHD as well as autoimmune diseases.


3.1.3. Wet Flood-Proofing

Wet flood-proofing measures allow floodwater to enter a building but limit the damage to the structure and its contents (Figure 1). This minimizes the risk that the walls of the house will collapse due to hydrostatic pressure from rising floodwaters on the outside. Measures include, for example, building utility installations and high-value areas above flood levels, raising electrical sockets, fitting tiled floors so that the building can quickly be returned to use after the flood, and sealing walls with water-resistant building materials [16]. For an extended table of individual flood-proofing measures, see Appendix B Tables A2 and A3. Construction cost for wet flood-proofing are presented in Table 3 and range between \$2412 for residential structures and \$34,070 for office buildings. The cost for flood-proofing office buildings is usually higher, as office buildings are relatively large, and the value of building contents is higher than that of residential buildings. Wet flood-proofing the basement of a residential building costs around \$35–206/m2. Maintenance costs are low—estimated at <1% of the total investment cost [26]. The cost of flood-proofing a 1500-L oil tank against buoyancy, buried in the garden, is estimated at \$1550 [27].

Brazil Residential n.a. \$962 2010 \$1024 n.a. [35] Vietnam Residential (60 m2) +1 m \$248 2014 \$273 n.a. [18] P Germany Oil tank Proofing against buoyancy \$1210/tank 2011 \$1550 n.a. [27] P


*4.1. Datasets*

In this work, we selected the BoT-IoT and TON-IoT datasets because they have been simulated to represent realistic IoT environments such as smart homes and cities. The datasets had a heterogeneity of simulated IoT devices including weather-monitoring systems, smart lights, smart thermostats, and a variety of cyber threats.


**6. SCD due to diabetes-induced autonomic system neuropathy and brady-arrhythmias**

The heart is innervated by the nerves of the autonomic nervous system (ANS) [15]. The ANS consists of sympathetic and parasympathetic nerves which innervate the heart. The parasympathetic or vagus nerve originates from the inhibitory center in medulla of the brainstem. The vagal nerve innervates mainly the atria (sinoatrial node) and the atrio-ventricular node (see **Figure 2**). Upon stimulation, it releases the neurotransmitter, acetylcholine (ACh). The main function of ACh is to activate cholinergic muscarinic receptors in the heart muscles leading to reductions in

**139**

**Figure 3.**

*MGO = methylglyoxal, a reactive carbonyl species.*

*Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death*

tandem to maintain the neural homeostasis of the heart [16].

conduction of impulse (negative dromotropic effect), rate (negative chronotropic effect), contraction (negative inotropic effect) and metabolism of the myocardium. On the other hand, the sympathetic nerve originates from the thoracic region of the spinal cord and it innervates the whole heart. It releases the neurotransmitter noradrenaline (norepinephrine) (NA) which activates beta-1–adrenergic receptors in the heart leading to increases in conduction of impulse (positive dromotropic effect), rate (positive chronotropic effect), contraction (positive inotropic effect) and enhanced metabolism of the myocardium. The two nerves of the ANS work in

**Figure 3** illustrates the relationship between diabetes-induced cardiac autonomic system neuropathy and brady-arrhythmias in SCD. In diabetes-induced cardiac autonomic neuropathy, the sympathetic nerve to the heart is damaged and its activity is reduced leading to slowing of the heart or brady-arrhythmias, heart rhythm disturbances and even SCD. Moreover, diabetes can also downregulate the beta-adrenergic receptor in the myocardium which in turn synergizes the brady-arrhythmias leading to cessation of the heart or SCD. There is new evidence that diabetes-induced cardiomyopathy is common and there is an increased risk of arrhythmias as a result of dysfunction of the cardiac conduction system (CCS) [17, 18]. This is due mainly to hyperglycemia-induced fibrosis which results in

*Flow diagram showing the cellular and molecular events in the myocardium due to diabetes-induced hyperglycemia culminating in Brady-arrhythmias and subsequently SCD. ROS = reactive oxygen species;*

*DOI: http://dx.doi.org/10.5772/intechopen.93729*

#### *Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death DOI: http://dx.doi.org/10.5772/intechopen.93729*

*Sudden Cardiac Death*

**Figure 2.**

*courtesy www.beyondbiology.org).*

preventing backflow. In turn, the right atrium receives retuning deoxygenated blood from the body through the superior and inferior vena cavae, while the left atrium receives oxygenated blood from the lungs through pulmonary vein. The heart itself needs a good supply of blood via the coronary arteries. These include the left anterior descending coronary artery, the left circumflex artery and the right coronary artery supplying the myocardium with oxygen-rich blood. The apex of the

*Diagram showing the electrical system of the mammalian heart with the conducting tissues including the SA node, AV node and Purkinje fiber network. SCD is usually caused by abnormal heart rhythms called arrhythmias and the most common life-threatening arrhythmia is ventricular fibrillation, which is an erratic, disorganized firing of impulses from the ventricles (see lower chambers with Purkinje network of fibers). When this occurs, the heart is unable to pump blood, and death will occur within minutes, if left untreated (image*

heart is the pointed end and the other end is called the base of the heart [13]. The orderly events that take place during the cardiac cycle are controlled by the electrical conduction system of the heart (**Figure 2**). An impulse is initiated at the sinoatrial node (SA-node) and then passes on to the atrioventricular node (AV-node) via conducting fibers via the atria. From the AV node, the impulse is conducted throughout the ventricles via the Purkinje fibers resulting in depolarization of the heart. Damage to the conducting tissues can result in sudden arrhythmias and possible SCD. Blood is pumped by the right ventricle into the pulmonary circulation at a lower pressure than blood pumped by the left ventricle into the systemic circulation. It follows that the haemodynamic stresses in the right and left side of the heart are very different. Even within the ventricles, the electro-mechani-

cal properties of ventricular cardiac myocytes vary trans-murally [14].

**6. SCD due to diabetes-induced autonomic system neuropathy and**

The heart is innervated by the nerves of the autonomic nervous system (ANS) [15]. The ANS consists of sympathetic and parasympathetic nerves which innervate the heart. The parasympathetic or vagus nerve originates from the inhibitory center in medulla of the brainstem. The vagal nerve innervates mainly the atria (sinoatrial node) and the atrio-ventricular node (see **Figure 2**). Upon stimulation, it releases the neurotransmitter, acetylcholine (ACh). The main function of ACh is to activate cholinergic muscarinic receptors in the heart muscles leading to reductions in

**138**

**brady-arrhythmias**

conduction of impulse (negative dromotropic effect), rate (negative chronotropic effect), contraction (negative inotropic effect) and metabolism of the myocardium. On the other hand, the sympathetic nerve originates from the thoracic region of the spinal cord and it innervates the whole heart. It releases the neurotransmitter noradrenaline (norepinephrine) (NA) which activates beta-1–adrenergic receptors in the heart leading to increases in conduction of impulse (positive dromotropic effect), rate (positive chronotropic effect), contraction (positive inotropic effect) and enhanced metabolism of the myocardium. The two nerves of the ANS work in tandem to maintain the neural homeostasis of the heart [16].

**Figure 3** illustrates the relationship between diabetes-induced cardiac autonomic system neuropathy and brady-arrhythmias in SCD. In diabetes-induced cardiac autonomic neuropathy, the sympathetic nerve to the heart is damaged and its activity is reduced leading to slowing of the heart or brady-arrhythmias, heart rhythm disturbances and even SCD. Moreover, diabetes can also downregulate the beta-adrenergic receptor in the myocardium which in turn synergizes the brady-arrhythmias leading to cessation of the heart or SCD. There is new evidence that diabetes-induced cardiomyopathy is common and there is an increased risk of arrhythmias as a result of dysfunction of the cardiac conduction system (CCS) [17, 18]. This is due mainly to hyperglycemia-induced fibrosis which results in

#### **Figure 3.**

*Flow diagram showing the cellular and molecular events in the myocardium due to diabetes-induced hyperglycemia culminating in Brady-arrhythmias and subsequently SCD. ROS = reactive oxygen species; MGO = methylglyoxal, a reactive carbonyl species.*

dysfunction of the CCS in the diabetic heart (see **Figure 2**). Moreover, it was demonstrated by Zhang et al. [18] that diabetes-induced fibrosis of the heart was associated with the reduction of potassium channel (HCN4), Cav1.3, Cav3.1 (calcium channel), NCX1, (sodium-calcium exchanger) and connexin (Cx45) protein expression in the sinoatrial node of the heart which in turn resulted in brady-arrhythmia and possibly SCD [18]. Moreover, reduced ryanodine (RyR2) and sodium-calcium exchanger (NCX1) protein expression in the atrio-ventricular junction of the heart (AVJ) is believed to contribute in part to the prolongation of the PR interval. Similarly, reduced protein expressions of RyR2, NCX1, Cx40, Cx43, and Cx45 in the Purkinje fibers (PFs) are responsible for the prolongation of QRS complex. The downregulation of neuro-filament M sub-unit (NF-M) and β1 adrenergic receptor could also be linked to the reduced autonomic nervous control of the heart [17, 18]. All these cellular and molecular processes subsequently result in cardiac arrhythmias, QT interval prolongation and SCD of diabetic patients [19].


**1. Introduction**

238 Sustainable Forest Management – Case Studies

Xunta de Galicia. (1992). Plan Forestal de Galicia. Consellería de Agricultura, Gandería e

Xunta de Galicia. (2001). *O Monte Galego En Cifras*. Dirección Xeral de Montes e Industrias

Xunta de Galicia. (2010). Produción e Industrias. Subastas. Date of Access: July 26, 2011.

<http://mediorural.xunta.es/es/areas/forestal/produccion\_e\_industrias/subastas/>

Forestais, Consellería de Medio Ambiente, Xunta de Galicia

Compostela, España.

Available from:

Montes. Dirección. Xeral de Montes e Medio Ambiente Natural. Santiago de

Sustainable forest management is conceptualized as a management system which attempts to conciliate economic, ecological, and social dimensions (Maes et al., 2011; Vierikko et al., 2008). In this direction, sustainable forest management will have to foresee mechanisms and institutional arrangements for resolving trade-offs among multiple actors with conflicting interests (Bernués et al., 2005; Van Gossum et al., 2011). Decisionmaking schemes that involve a variety of interest groups might lead to increased complexity due to the societal demand for rational and transparent deliberation processes (Brechin et al., 2002; Wolfslehner & Seidl, 2010). A major challenge to sustainable forest management is to handle this complexity as well as confront uncertainty, which originates from changes in positions of stakeholders, scientific theories, and social institutions (Foster et al., 2010).

One response to complexity is to employ adaptive management, which presupposes feedback mechanisms and reflexive learning processes as necessary prerequisites to cope with an undetermined future and the core issues of risk and uncertainty (Plummer & Fennell, 2009; Von Detten, 2011). However, social aspects of sustainability are frequently downplayed even in adaptive management configurations. Previous studies showed that conventional methods of social science research and widely implemented management policies might underestimate the social heterogeneity at the local level to a substantial extent (Berninger et al., 2010; Sugimura & Howard, 2008). This inadequate handling of the social context might be expressed in matters of environmental governance. For instance, when local communities are represented by spokespersons adhering to majorities, minority positions are excluded (Hovardas et al., 2009; Hovik et al., 2010).

In the present paper we will approach the notion of sustainable forest management critically by examining the case study of the Dadia-Lefkimi-Soufli Forest National Park (DNP) in Greece. Our basic objective is to exemplify how forest management in a protected area can succeed in guaranteeing viable population sizes of endangered species but, at the same time, how it can eventuate in new risk situations regarding fire suppression and ecotourism development. Next, we will present a mixed-motive perspective formulated by local

Can Forest Management in Protected Areas Produce New Risk Situations?

(Poirazidis et al., 2004; Skartsi et al., 2008).

including the celebration of the Annual Birds' Day.

**2.1 Fire suppression in DNP**

2004; Vasilakis et al., 2008).

A Mixed-Motive Perspective from the Dadia-Soufli-Lefkimi Forest National Park, Greece 241

the Balkans (Skartsi et al. 2010). The two cores have 85% cover of pinewoods and mixed pine-oak woods and are crucial as nesting sites for the black vulture (Poirazidis et al., 2004). Maps of probability of occurrence for the nest sites of black vultures showed that nests are very likely to fall within the cores of DNP (Poirazidis et al., 2004). While the population in 1979 amounted to no more than 5 breeding pairs and a total of 26 individuals, the number of birds counted today in the park may range between 70 and 80 individuals, including about 20 breeding pairs (Skartsi et al., 2010). A number of projects implemented by WWF-Greece supported the increase of the population of the black vulture (Adamakopoulos et al., 1995; Poirazidis et al., 2002), for instance, vulture food supplement is provided in a feeding table that has been landscaped in the big core of the study area. Together with vulture food supplement, prohibition of hunting as well as strict control of forestry activities and road access that may lead to breeding failure have enabled the recovery of the black vulture

When the protected area was established in 1980, local people opposed fiercely the suspension of logging in the core zones of the forest reserve, since the loggers' cooperative in Dadia included more than 70 members, namely, about one-tenth of the total population of the village (Catsadorakis, 2010). This negative stance gradually shifted to an acceptance of the environmental conservation regime principally due to ecotourism development (Hovardas & Stamou, 2006a; Svoronou & Holden, 2005). The primary sector is currently decreasing in terms of employment, while the tertiary sector, including services and tourism, is gaining importance in the local economy (Liarikos, 2010). Ecotourism has been developed around wildlife viewing. Visitors are transferred to a Bird Observatory in full view of the vulture feeding table, where they can watch vultures feeding on carcasses (Hovardas & Poirazidis, 2006). The annual number of visitors has risen from less than 2000 in 1994 to more than 40000 today and infrastructure was gradually expanded to cover the rising demand (Hovardas, 2005). Apart from supporting ecotourism development, WWF-Greece has launched since the 1980s a series of environmental awareness campaigns

The biodiversity in DNP has to be attributed to a highly heterogeneous patchwork of habitats which are the result of traditional activities such as livestock grazing, small-scale agriculture and logging, as well as the use of fire (Grill & Cleary, 2003; Kati & Sekercioglu, 2006). However, many of these anthropogenic activities have either diminished or are undertaken rather infrequently (Schindler, 2010). Analogous socio-environmental trends have been reported for other Mediterranean mountainous regions (Álvarez Martínez et al., 2011; Badia et al., 2002; Bernués et al., 2005; Tàbara et al., 2003). In accord with the regulation of logging activities after the designation of DNP, the developments that have been described above have resulted in forest expansion and a decrease of forest clearings (Triantakonstantis et al., 2006), which comprise a crucial structural component of the foraging habitat of vultures (Catsadorakis et al., 2010; Gavashelishvili & McGrady, 2006). Therefore, protected area managers in DNP call for an urgent restoration of traditional activities with special reference made to grazing, which can halt the accumulation of dry plant biomass and reduce the risk of a wildfire (Catsadorakis et al., 2010; Poirazidis et al.,

residents, who take advantage of the new risk situations encountered in the area and aim at the renegotiation of forest management and building a new social consensus. Finally, we will attempt a philosophical grounding of the mixed-motive perspective and we will discuss its potential contribution in promoting a new conceptualization of sustainability in forest management.


**1. Introduction**

The competitive nature of the current chemical industry constantly demands improvements in process and product quality and efficiency. To maximize profitability and to succeed in the global competition, the chemical processes need to be operated optimally and also need to look for better products and ways to produce them. Process Systems Engineering (PSE) tools have been instrumental

in developing optimal processes and identifying better products. PSE is defined by Grossmann and Westerberg [1] as "the field that is concerned with the improvement of decision-making processes for the creation and operation of the chemical supply chain. It deals with the discovery, design, manufacture, and distribution of chemical products in the context of many conflicting goals." The developed approaches towards chemical process design is a major shift from the conventional focus where the emphasis was to develop tools and procedures for the process design, control, and operation. In recent decades, the focus of research in PSE fields has shifted to the areas of development of new products, process networks and enterprise, supply chain optimization, and global life cycle assessment (LCA) [2].

The development of PSE tools and methodologies has enabled the applications of these tools in various research fields. While the focus of PSE tools was more process-oriented and towards specific industrial problems in the twentieth century, the effect of globalization has prompted researchers to extend the PSE tools into new areas, e.g., development of new products, process intensification, and to address sustainability challenges. Significant improvements in computational efficiency have contributed to the application of PSE tools in several areas where historically, size-related problems had made the solutions impractical. In this paper, the application of novel PSE approaches in the design of ionic liquids and the synthesis of integrated biorefineries are highlighted. Since these are relatively recent concepts, specific PSE tools had to be developed to address the specific/novel challenges raised by these problems.

It has been recognized in recent years that ionic liquids may be a suitable replacement for several traditional solvents that pose environmental risks. The major potential areas for their application as a solvent include carbon capture, extraction, as an entrainer in extractive distillation, and also in various chemical, biochemical, electrochemical, and pharmaceutical industries [3]. Ionic liquids have unique properties that make them suitable for these industrial applications. In addition, it is possible to alter the functional groups to meet the desired attributes for various applications. The two major challenges for the design of suitable ionic liquids and the application in industries are the unavailability of reliable data and the high production cost of ionic liquids. Because of that, the ionic liquids used for various applications and the conditions at which the systems are operated may not be optimal. In order to make an optimal selection of ionic liquids, various PSE approaches (both insight-based and mathematical optimization approaches) have been developed in the past decades. The development of novel group contribution (GC) models [3], computer-aided molecular design (CAMD) tools [4], and the development of quantum mechanical (QM) tools that can be integrated with CAMD approaches [5] had been the significant breakthroughs that allow the application of PSE tools in the ionic liquid design and selection.

In addition to the design and selection of ionic liquids, the development and application of PSE tools in the field of integrated biorefineries have been immense. In recent years, biomass utilization has shown promising results in addressing society's dependence on non-renewable energy resources and climate change caused by fossil fuel exploitation. Other than being utilized for heat generation through direct combustion, the nature of biomass enables it to be converted into other value-added products ranging from biomaterials, biofuel, bio-chemicals, biopharmaceuticals, etc. Through different biomass conversion technologies (physical, mechanical, chemical, and biological), biomass can be converted into other forms of energy products such as transportation fuels, or value-added products like commodities and specialty chemicals. In the past decades, the development of single biomass conversation systems such as gasification, fermentation, digestion, etc., has been established. However, due to the complexity and diversity of biomass in nature, a single biomass conversion system is typically not able to fully recover the potential of the biomass. In view of this, integrated biorefineries is a fast-developing research area that integrates a variety of technologies to convert biomass into the abovementioned value-added products [6]. As integrated biorefinery is able to integrate multiple technologies as a single integrated system, such a system provides more flexibility in product generation and generates sufficient energy to support the entire operation and reduce the overall energy consumption compared to the processes that operate independently. In addition, with the integration of multiple technologies, the waste/by-products can be used as feedstock for another process, therefore, the material recovery can be maximized as shown in Figure 1. Various research works [6–10] have been presented to optimize the synthesis and design of integrated biorefineries, ranging from insight-based approaches to complex mathematical optimization models, which is discussed in Section 3.

**Figure 1.** The integrated biorefinery concept.

In summary, advances in computing, data science, and optimization have allowed researchers to extend the application of PSE tools in several novel areas. In this paper, the application of PSE tools in the synthesis and design of ionic liquids, as well as integrated biorefineries, are to be reviewed. A general overview of these two research areas is provided followed by a detailed review of the recent development and application of PSE tools in the area. The major research challenges and the approaches used by the PSE community in addressing the identified challenges are highlighted in this paper. This review also focuses on the integration of these research fields where the role of ionic liquids as solvents in integrated biorefineries has been analyzed. Finally, the paper identifies some of the research scopes for further research and the way forward.


**5. Age-Associated Microbial Dysbiosis**

In addition to the impaired function of the local immunity and increased gastrointestinal mucosa permeability, age associated alterations of the gut microbiota may also favor FA development in the elderly.

The gut microbiota is a complex ecological system that exerts a central role in several physiological functions, and its composition changes throughout the host's life. It is sensitive to environmental influences and the host's diet, and depends on the host's genetics, gender, and the aging process per se [51].

The system of the secretory IgA plays a critical role not just for the defense against infections but also for the modulation of local immune responses through the maintenance of the intestinal microbiota. Inflammatory processes are associated with dysregulation of the homeostatic interactions between the intestinal microbiota and the aging host [52].

Intestinal microbiota exhibit significant age-associated changes in composition and diversity, as well as in functional features, mainly caused by the immune system remodeling and low-grade chronic inflammation, which respectively characterize immunosenescence and inflammaging [22].

Immunosenescence exerts a key role by modifying the host's response to microbiota, triggering inflammaging, and shifting Th1 versus Th2 responses, thus favoring tolerance dysruption and allergic reaction development [52].

Antibiotics are among the most commonly used drugs in the elderly and are often used improperly. They influence the microbiome composition and function interfering with immune homeostasis. In the geriatric age, antibiotics can further disturb the composition of the microbiota [53,54]. However, even in

the elderly, the intestinal flora can be reconstituted by probiotics, but it is not yet known how this can prevent the development of FAs [55].

#### **6. Immune Dysfunctions Due to Nutritional Deficits**

Together with the peculiar remodeling of the immune system during senescence, the compromised integrity of epithelial barriers and the sub-clinical chronic inflammatory condition commonly observed in the elderly, a central role in sensitization to food allergens is also played by the lack of micronutrients and vitamins [12].

Micronutrients and antioxidants modulate immune responses and it is suggested that their deficits favor the development of Th2 type responses. For example, deficits of iron, zinc, and vitamin D, which are very common in the elderly, may represent additional risk factors for the onset of allergic reactions during senescence [10].

Zinc is an essential trace element that plays a central role regarding the immune efficiency. Zinc intracellular homeostasis, regulated by metallothioneins and specific transporter proteins, is altered in aging, leading to its decreased availability for immune functions. A reduced zinc level, frequently observed in the elderly, could be responsible for a decreased production of Th1 cytokines, whereas this does not affect the production of Th2 cytokines, thus inducing a cytokine imbalance that promotes the development of allergic diseases [56].

Zinc deficiency contributes to thymic atrophy; immature B cell accumulation; and decreased IgM, Ig-G2a, and IgA subclasses. Stress situations, through pro-inflammatory cytokine production, including IL-6 and TNF-α, are often associated withzinc deficiency. Inflammatory cytokines, permanently increased in the geriatric population, bind zinc ions with a consequent reduced zinc bioavailability and altered immune functions. In particular, decreased levels of zinc induce a reduction of Th1 cytokines, such as IFN-γ, IL-2, and TNF-α, while Th2 cytokines, in particular IL-4, are enhanced. Through this mechanism, zinc deficiency could favor the development of FAs in the elderly [57].

Iron deficiency is also frequent in the elderly [20]. The decreased iron level induces impaired humoral responses, and in particular reduces the production of the IgG4 subclass that physiologically captures the allergens before they can bind to the IgE, thus preventing the activation of effector cells, such as mastocytes and basophils [58].

Several studies suggest that vitamin D deficiency is also very common in the elderly, supporting FA development. Immune dysregulation, in addition to an increased parathyroid hormone level and impaired bone health resulting in enhanced risk of fractures, is a serious consequence of vitamin D deficiency in the elderly [59,60]. The active metabolite of vitamin D, calcitriol, influences T lymphocytes and antigen-presenting cells to induce peripheral tolerance by inhibiting inflammatory responses and promoting regulatory T cells [61]. Vitamin D deficiency is therefore associated with an increased risk of autoimmune and atopic diseases, although the association with IgE levels is not clear [62].

#### **7. Clinical Features of FAs in the Elderly**

The variable natural history and the complexity of the possible pathogenetic mechanisms, as well as several age-associated factors, make the diagnosis and management of FAs in the elderly difficult. Nutritional abnormalities and vitamin deficiencies, as well as hormonal imbalances and inflammaging, interacting with genetics, may alter the immune responses, leading to FA development. The age-related decline of physiological functions, in addition to the immune system remodeling, which characterizes senescence, contribute to confer peculiar clinical findings to FA in the elderly [23,63].

Furthermore, despite the normal or increased number of mast cells in the skin of aged subjects with an allergy and a sufficient positive response to prick tests with specific allergens, elderly show weaker cutaneous responses and less intense pomfoid reactions to histamine control [64]. Therefore, since the positive reactions to skin test for an allergy could be partially reduced in the elderly, creating possible risk of false negative skin test, a specific IgE search to diagnose FA is commonly used in older patients [65].

Frailty, comorbidity, and multi-drug intake are conditions commonly found in the elderly and must be taken into account in the management of aged people affected by FAs. Immunologic reactions to foods can be confused with symptoms of other common age-related diseases or be masked by the use of various drugs. Consequently, the characteristic symptoms of FAs often go unnoticed and this contributes to underestimating FA prevalence in old age [7]. Dryness and hyperkeratosis, with consequent itching and increased risk of skin infections, are dermatologic manifestations that often mimic and/or mask the symptoms of an allergy. Cutaneous symptoms, such as atopic dermatitis and urticaria, could also represent manifestations of FAs in the elderly [25]. However, in addition to FAs, even drugs and systemic diseases, mainly hematologic and immune dysfunctions, can also induce urticaria in the elderly. Underlying diseases must, therefore, always be suspected, especially when a new diagnosis of chronic urticaria is made in an elderly person [66,67]. Although aged individuals can respond to immunotherapy for a respiratory allergy, as well as to biological drugs commonly used for the treatment of allergic manifestations, such as urticaria and atopic dermatitis, they are usually excluded from these kinds of therapy [68,69]. This is due to the frequent presence of age-related clinical conditions that are considered contraindications. Moreover, the common occurrence of comorbidities and multidrug intake can affect the therapeutic response and promote the onset of side effects. However, immunotherapy and biologic drugs could also significantly improve the quality of life in the elderly, reducing symptoms and drug consumption [70].

Anaphylaxis is a severe and life-threatening hypersensitivity reaction that can affect allergic patients at any age [45]. Clinical manifestations of anaphylaxis caused by food allergens are less frequent in the elderly compared to young subjects [71]. However, although less common, anaphylaxis exhibits a worst prognosis in older patients [72]. The anaphylaxis mediators released by the mast cells after the binding of the allergen to the IgE anchored to their surface induce profound functional modifications on the cardiocirculatory system, including vasospasms of coronary arteries with reduced myocardial blood flow and arhythmias [10,73]. The age-related susceptibility of the cardiovascular system to mast-cell-derived mediators and underlying comorbidities, such as coronary diseases, contribute to the increased mortality and frequent cardiovascular involvement during anaphylaxis in aged people [74]. In patients with multimorbidities, multidrug prescriptions are important cofactors complicating anaphylactic events in the elderly [75]. Cardiovascular drugs, increasingly prescribed to the elderly, strongly contribute to thegreater probability of a fatal outcome. Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, commonly used to treat congestive heart failure and hypertension, may in fact contribute to aggravate the impairment of compensatory mechanisms typical of the elderly [76]. Several other drugs may interfere with allergic effector cells of FAs. Nonsteroidal anti-inflammatory drugs, taken for chronic osteoarticular pain, are relevant cofactors in urticaria and anaphylaxis in aged subjects [67]. Tricyclic antidepressants, monoamine oxidase inhibitor, and neuroleptics may increase the cardiac risk of epinephrine administration. All these different drugs could cause hypotension, accelerate and increase exposure to allergens, and mask the symptoms of a possible allergic reaction. Although the advanced age doesnot represent an absolute contraindication to self-injectable adrenaline prescription in those at higher risk of anaphylaxis, impaired neuro-motor coordination, frequent hypomobility, and the common coexistence of osteo-muscular and arthrosic hand pathologies compromise the ability to use auto-injectors, suggesting caution in this prescription [77].

The intake of antiulcer drugs is common in the elderly to cure gastritis, gastroesophageal reflux, gastric ulcers, or in association withcorticosteroids and non-steroidal painkillers to minimize their gastrolesive effects. Gastric hypoacidity and increased permeability of the upper gastrointestinal tract also occur as a result of therapy with acid-suppressive drugs, facilitating the onset of an FA, as well as eosinophilic esophagitis. Elderly patients treated with proton pump inhibitors or H2-receptor blockers are at higher risk for sensitization because dietary proteins both remain incompletely digested and can cross the mucosal barrier more easily due to the increased permeability, thus becoming allergenic [8,49].


*Article* **Risk-Based Methodology for Determining Priority Directions for Improving Occupational Safety in the Mining Industry of the Arctic Zone**

**Semyon Gendler and Elizaveta Prokhorova \***

> Department of Industrial Safety, Saint Petersburg Mining University, 2, 21st Line, 199106 St. Petersburg, Russia<EMAIL_ADDRESS>
**\*** Correspondence<EMAIL_ADDRESS>
**Abstract:** Over the past 10 years, the mining industry of Russia has seen a greater than threefold decrease in injury rates, thanks to the successful implementation of innovative labor safety technologies. Despite this, injury levels remain unacceptably high compared to the leading mining countries, which results in increased mining costs. For the mining areas of the Arctic Zone—unlike other regions located in areas with a more favorable climate—the injury rates are influenced not only by the underground labor conditions, but also by the adverse environmental factors. For the Russian Arctic zone, the overall injury risk is proposed to be calculated as the combined impact of occupational and background risk. In this article, we have performed correlation analysis of the overall injury risks in regions of the Arctic zone and regions with favorable climate conditions. Using the Kirov branch of "Apatit", Joint-stock company (JSC) as an example, we have calculated the risks related specifically to occupational injury rates. We have constructed the relative injury risks and their changes over time and have developed a "basic injury rate matrix" that makes it possible to visualize the results of the comparative analysis of the injury rates on the company's production sites and to determine priority avenues for improving the occupational safety and lowering the injury rates.

**Keywords:** arctic zone; mining industry; mines; labor safety; occupational injury rate; risk-based methodology; risk of injuries; injury risk diagram; correlation analysis


**Author details**

Daniela Cornelia Lazar1 \*, Elena-Alina Moacă2 , Mărioara Cornianu3 , Sorina Tăban3 , Alexandra Faur4 and Adrian Goldiș5

1 Department of Internal Medicine I, University of Medicine and Pharmacy "Victor Babeș" Timișoara, Romania

2 Department of Toxicology, Drug Industry, Management and Legislation, University of Medicine and Pharmacy "Victor Babeș" Timișoara, Romania

3 Department of Pathology, University of Medicine and Pharmacy "Victor Babeș" Timișoara, Romania

4 Department of Anatomy and Embriology, University of Medicine and Pharmacy "Victor Babeș" Timișoara, Romania

5 Department of Gastroenterology, University of Medicine and Pharmacy "Victor Babeș" Timișoara, Romania

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 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.


*Edited by Karl Almqvist,*

*Ahmed Ebrahim El Hamaky*

*and Taiceer Abdulwahab*

Over the past few decades, there have been significant advances in our understanding of the pathophysiology of cartilage disorders, for example, the characterization of degraded cartilage using Confocal Raman Microscopy as well as the evolution of cartilage repair technologies. Cartilage disorders are complex and multifactorial, and they can cause significant pain and disability in affected joints/individuals. As such, it is essential for orthopedic surgeons to have a thorough understanding of the latest research and treatment options to provide the best possible care to their patients. This book provides a comprehensive overview of the latest research and treatment options in cartilage disorders. It presents cutting-edge research, technologies, and treatment options for orthopedic surgeons. Organized into two sections, the chapters of this book address such topics as the evaluation and management of patients with cartilage injuries, imaging and biomarker technologies, techniques to repair and regenerate damaged cartilage, and more.

ISBN 978-1-83769-984-1

Cartilage Disorders - Recent Findings and Treatment

Published in London, UK © 2023 IntechOpen © tonaquatic / iStock

## Cartilage Disorders Recent Findings and Treatment

*Edited by Karl Almqvist, Ahmed Ebrahim El Hamaky and Taiceer Abdulwahab*


*3.1.1 Evidence of ginger's anti-COVID-19 properties*

SARS-CoV-2-related papain-like protease (PLpro) cleaves polyprotein a/b (PP a/b) at different sites yielding several proteins needing for viral survival and replication (**Figure 2**) [17]. SARS-CoV-2-related PLpro also interferes with type I IFN anti-virus response [17]. In order to successfully suppress virus multiplication and survival, anti-SARS-CoV-2 medications should target PLpro. [18]. According to the findings of a study conducted in Saudi Arabia, COVID-19 patients' consumption of ginger increased from 36.2% prior to infection to 57.6% after infection. The proportion of patients admitted to the hospital for COVID 19 treatment was also lower (28.0%) among ginger users than among nonusers (38.0%) [19]. A few examples of cured COVID-19 patients were recorded in a Bangladesh study, who drank home medicines using ginger in blends of various herbs with or without further treatments [20]. A few cases of COVID-19 were treated with home remedies including ginger in combination with other herbs improved disease symptoms, according to the findings of a Tunisian study [21]. In certain African countries, renowned treatments involving ginger in combinations with other herbs were also utilized to treat COVID-19 [22]. In compared to those treated with a normal protocol using hydroxy-chloroquine alone, the results of an Iranian clinical trial study show that combining outpatients with probable COVID-19, ginger and Echinacea alleviated some of their clinical symptoms (breath shortness, coughing, and muscular discomfort) [23]. Ginger may help patients with pulmonary problems such ARDS (Acute respiratory distress syndrome), fibrosis, lung and pneumonia, as well as sepsis, which are all indications seen in COVID-19. Overall, the evidence suggests that more high-quality controlled trials are needed to validate ginger's benefit and safety in COVID-19 patients. In Iran, a clinical investigation is underway in which 84 COVID-19 patients were randomly assigned to two groups, each with 42 participants, including intervention and control groups [24]. The intervention group will receive standard treatment plus 1000 mg ginger three times daily for seven days, whereas the control group will receive normal treatment plus placebo tablets at the same dose and schedule for seven days [16].

#### **Figure 2.**

*COVID-19 pathogenesis is influenced by SARS-CoV-2 and inflammation. SARS-CoV-2 infects tissues that express ACE2, causing necrosis, pyroptosis and apoptosis, as well as inflammation. Infected macrophages with SARS-CoV-2 release a variety of cytokines and chemokines, causing tissue inflammation and a cytokine stormTLRs and inflammasomes can be activated by SARS-CoV-2, resulting in an increase in inflammatory responses and tissue damage. Ginger can enhance antiviral immune responses and have direct anti-SARS-CoV-2 effects, as well as interfere with inflammatory responses mediated by macrophages, TLRs, and inflammasomes. Abbreviations: ALI: Acute lung injury; ACE2: Angiotensin-converting enzyme 2; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ARDS: Acute respiratory distress syndrome; TLR: Toll-like receptor; IL: Interleukin [16].*


**Evaluation of Supply–Demand Adaptation of Photovoltaic–Wind Hybrid Plants Integrated into an Urban Environment**

#### **Africa Lopez-Rey \*, Severo Campinez-Romero, Rosario Gil-Ortego and Antonio Colmenar-Santos**

Department of Electric, Electronic and Control Engineering, UNED, Juan del Rosal, 12-Ciudad Universitaria, 28040 Madrid, Spain<EMAIL_ADDRESS>(S.C.-R<EMAIL_ADDRESS>(R.G.-O<EMAIL_ADDRESS>(A.C.-S.)

**\*** Correspondence<EMAIL_ADDRESS>Tel.: +34-913-987-798

Received: 8 April 2019; Accepted: 6 May 2019; Published: 10 May 2019

**Abstract:** A massive integration of renewable energy sources is imperative to comply with the greenhouse emissions reduction targets fixed to achieve the limitation of global warming. Nevertheless, the present integration levels are still far from the targets. The main reason being the technical barriers arising from their non-manageable features. Photovoltaic and wind sources are the widest spread, as their maturity allows generation with a high-efficiency degree. A deep understanding of facilities' performance and how they can match the energy demand is mandatory to reduce costs and extend the technical limits and facilitate their penetration. In this paper, we present a novel methodology to evaluate how photovoltaic–wind hybrid facilities, placed in an urban environment can give generation patterns which will be able to match the demand profiles better than facilities installed individually. This methodology has been applied to a broad number of locations spread over the whole planet. The results show that with high homogeneity in terms of site weather characteristics, the hybrid facilities improve the matching up to 15% over photovoltaic plants and up to 35% over wind.

**Keywords:** wind energy; photovoltaic; complementarity; grid integration


*4.1. The Economic Impacts of Connectivity in the Mekong Subregion*

The coordinated development of soft and hard infrastructure is also essential to maintain growth in the region. The new international division of labor calls for a novel approach to infrastructure development, in which the Mekong Subregion is prepared to participate actively in the promotion of economic corridors: the Southern Economic Corridor, the EWEC, and the North–South Economic Corridor. These economic corridors—together with the fast acceleration of domestic infrastructure development including SEZ, urban amenities, and other economic activities—have already promoted regional participation in the production network by reducing the cost of service links that connect remote locations. Mekong Subregion connectivity is just one piece of the puzzle in ASEAN connectivity with the rest of the world. China's BRI is another very large 'connectivity for development' strategy, linking China to Eurasian countries and the rest of Asia.

As the region embarks on rapid infrastructure development, quality infrastructure, connectivity, and innovation are key to ensure prosperity and sustainable development. Infrastructure development and stages of economic development can be explained by the development of recent economic theories: fragmentation theory and new economic geography [72]. The theory classifies infrastructure projects into three tiers. Tier 1 includes projects that serve countries/regions that are already in production networks and have started forming industrial agglomerations. Tier 2 consists of projects supporting countries/regions that are about to participate in production networks. Tier 3 consists of projects in remote areas where participation in production networks is difficult in the short run, but where better and more reliable connectivity can generate new business models in agriculture, mining, tourism, and other industries. Thus, the ultimate aim of quality infrastructure and services development is in tier 1, in which some ASEAN Member States are experiencing and enjoying quality growth, particularly Singapore and to some extent Brunei Darussalam. Malaysia and Thailand are also doing well, with the quality of infrastructure in tier 2 possibly moving to tier 1 in the near future. The Mekong Subregion has achieved lower middle-income status, improving infrastructure quality from tier 3 and possibly joining tier 2 in the near future. Indonesia and the Philippines have achieved middle-income status and infrastructure development is in the early stage of tier 2, likely catching Malaysia and Thailand in the near future.

By and large, connectivity and innovation promote agglomeration forces and dispersion forces generated by production–consumption interactions in both internal and external economies in which people and ideas can move easily. Agglomeration forces mean that economic activities and people are attracted to the core, where positive agglomeration effects are found in the form of the ease of finding business partners and proximity to the market, etc. On the other hand, dispersion forces generate movements of economic activities and people from the core to the periphery. One source of dispersion forces is negative agglomeration effects or 'congestion' in the core, which includes wage increases, land price hikes, traffic congestion, and environmental pollution [72].

One practical example of new economic geography creating 'location advantages' through connectivity and innovation is Cambodian labor force migration. Currently, about 1 million (out of a population of 16 million) Cambodians are in Thailand working in unskilled labor-intensive sectors and the informal sector rather than in Phnom Penh. The question is: How can Phnom Penh attract labor from rural areas and, at the same time, attract production blocks from Thailand? If the wage gap between Bangkok and Phnom Penh is too large, people will not move to Phnom Penh; however, at the same time, production blocks may be motivated to move. On the other hand, if the wage gap is too small, production blocks will not move even though people may flow into Phnom Penh.

Then, how can Phnom Penh attract both production blocks and people? The answer is the improvement of location advantages and liveability in Phnom Penh.

Another example is the Mekong–India Economic Corridor (MIEC)/EWEC connecting Ho Chi Minh (HCM) City, Phnom Penh, Bangkok Metropolitan Area, and Dawei. This has great potential to become a major manufacturing corridor in the near future. However, the question is how to attract labor and investment to Dawei. In this regard, the MIEC will need to have at least three projects implemented at the same time—industrial estates, highway connection to Thailand, and a deep seaport. According to Han [4], the road situation between Phnom Penh and HCM City was relatively bad in 1999. Before the road was upgraded, travel time from Phnom Penh to HCM City was about 9–10 h, and cross-border trade at Moc Bai (Vietnam)–Bavet (Cambodia) was worth about USD 10 million per year. However, the situation completely changed in 2014 after implementing hardware and software infrastructure between Phnom Penh and HCM City. The travel time was reduced to 5–6 h, and cross-border trade at Moc Bai–Bavet grew to USD 708 million per year [72]. Further, connectivity promoted other economic development corridors, such as investment brought to Trang Bang Industrial Park (in Moc Bai), consisting of 41 projects with USD 270 million in new investment, creating about 3000 jobs.

The top 10 beneficiaries from the MIEC, based on ERIA (2015), are Dawei, Phnom Penh, Dong Nai, Kawthoung, HCM City, Kandal, Sihanoukville, Banteay Meanchey, Svay Rieng, and Battambang. For Phnom Penh, it was estimated that the connectivity would increase gross domestic product (GDP) by almost 400% as a cumulative impact during 2021–2030. ERIA also estimated the remainder of the economic corridor in the Mekong Subregion, and found significant impacts for all participating countries in the connectivity.

For power connectivity in the Greater Mekong Subregion (GMS), ERIA's study on energy markets in ASEAN and East Asia examined the power trade and development in the subregion for the foreseeable future [73]. The study showed that the 2030 Scenario (in which the GMS realizes the potential of hydropower) will provide both economic and environmental benefits. The GMS at large will benefit by about USD 40 billion and reduce CO2 emissions by almost 70 million tons per year. For ASEAN power connectivity as a whole, the study estimated that ASEAN would save USD 25 billion over 20 years by substituting hydropower for fossil fuels.


**4. Conclusions**

**0**

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*C D*

+

*v*

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   *S*

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**300**

**450**

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**∆***T***m (K)**

**600**

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**900**

**4. Conclusions** The model-scale tunnel calculates the maximum temperature increase in the smoke The model-scale tunnel calculates the maximum temperature increase in the smoke under the interconnected tunnel by combining the velocity and HRR of the fire source under various blockage ratios. The following are the key conclusions of this paper:

under the interconnected tunnel by combining the velocity and HRR of the fire source under various blockage ratios. The following are the key conclusions of this paper: (1) The velocity of the ramps upstream of the fire source and the adjacent ramp have (1) The velocity of the ramps upstream of the fire source and the adjacent ramp have an impact on the maximum temperature rise in the interconnected tunnel. The maximum temperature rise is jointly impacted by both ramps' ventilation.

an impact on the maximum temperature rise in the interconnected tunnel. The maximum temperature rise is jointly impacted by both ramps' ventilation. (2) The maximum temperature rise in the interconnected tunnel varies with velocity and the blockage ratio. Depending on who is more impacted by the velocity or blockage (2) The maximum temperature rise in the interconnected tunnel varies with velocity and the blockage ratio. Depending on who is more impacted by the velocity or blockage ratio, the maximum temperature rise differs. The maximum temperature rise decreases, and the impact of the blockage ratio diminishes when the velocity in the interconnected tunnel decreases. This is because the convective heat transfer near the fire source increases.

ratio, the maximum temperature rise differs. The maximum temperature rise decreases, and the impact of the blockage ratio diminishes when the velocity in the interconnected tunnel decreases. This is because the convective heat transfer near the fire source in-(3) In an underground interconnected tunnel fire, the maximum temperature rise is influenced by the velocity upstream of the fire source and the adjacent tunnel. As a result, this research provides a novel method for predicting the maximum temperature rise under the underground interconnected tunnel that is blocked by vehicles.

creases. (3) In an underground interconnected tunnel fire, the maximum temperature rise is influenced by the velocity upstream of the fire source and the adjacent tunnel. As a result, We only studied blockage rates between 0% and 30% in this paper. Additionally, the angles between ramp C and ramp D were not considered. More research will be carried out in the next stage.

this research provides a novel method for predicting the maximum temperature rise under the underground interconnected tunnel that is blocked by vehicles. We only studied blockage rates between 0% and 30% in this paper. Additionally, the **Author Contributions:** Methodology, Z.X.; software, J.Z.; validation, H.Y.; formal analysis, H.Y.; investigation, H.Y.; resources, B.X.; data curation, Y.Z.; writing—original draft preparation, Y.Z.; writing—review and editing, S.M.S.T. All authors have read and agreed to the published version of the manuscript.

angles between ramp C and ramp D were not considered. More research will be carried out in the next stage. **Funding:** The Science and Technology Research and Development Program Project of China railway group limited (Major Special Project, No.: 2021-Special-04-2) funded this research.

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

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** We acknowledge the High-Performance Computing Center of Central South University for its support.

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


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pdf [Accessed: Oct 19, 2018]

2016;**11**(9):e0163108

2004;**27**:1047-1053

2012;**96**(5):614-618

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[Accessed: Oct 24, 2018]

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2018]

Oct 24, 2018]

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## *Edited by Anna Nowinska*

In the last 10 years, there has been huge progress in the general understanding of ocular disorders due to the availability and development of new in vivo imaging techniques, such as anterior and posterior eye segment optical coherence tomography as well as biochemical methods allowing rapid confirmation of clinical diagnosis. Introducing noninvasive diagnostic methods in ophthalmology led to an improvement in early differential diagnosis of conditions such as corneal dystrophies, dry eye disease, and various retinal and optic nerve diseases.Recent advances in diagnostic methods have also impacted the treatment methods.

This book intends to provide the reader with a comprehensive overview of current ocular diagnostic methods, including the theoretical basis as well as practical approaches and usage in clinical practice.

Published in London, UK © 2019 IntechOpen © uatp2 / iStock

Novel Diagnostic Methods in Ophthalmology

IntechOpen Book Series

Biomedical Engineering, Volume 6

Novel Diagnostic Methods in

Ophthalmology

*Edited by Anna Nowinska*


2.2.4. Analytical and Calculation Methods

Hydrocarbon composition of the feedstock and products was determined according to ASTM D 5134-13(2017) standard. Octane numbers of the feeds and products were calculated from their hydrocarbon composition and by blending octane numbers of the individual components. In order to evaluate the efficiency of isomerization and the yields of iso- and cyclo-paraffins, the thermodynamic equilibrium concentration (ATECT) was calculated according to Equation (1).

$$\text{ATEC}\_{\text{T}} = \frac{(\mathbf{c}\_{i-\text{Cx}})\_{\text{T}}}{(\mathbf{C}\_{i-\text{Cx}})\_{\text{T} \text{HT}}} \ast 100 \tag{1}$$

where (ci-Cx)T is the concentration of the isomer at the actual temperature in the C6 fraction of product, and (Ci-Cx)ThT is the equilibrium concentration of the isomer.

The Pt content of the catalysts was determined by the inductively coupled plasma (ICP) method; the platinum dispersion of catalysts was determined by CO pulse chemisorption, and CO consumption was detected by a thermal conductivity detector. The Al and Si contents of H-Mordenite were also determined by the ICP method. The specific surface areas were determined by the Brunauer–Emmett–Teller (BET) method from the corresponding nitrogen adsorption isotherm. The chlorine content of catalysts was measured by the Volhard method [26]; the sample was dissolved in concentrated sulfuric acid and Cl ions were precipitated with silver nitrate solution. Excess silver solution was back titrated with a thiocyanate solution to give the amount of chlorine in the original sample. The chlorine contents of products were determined according to the ASTM D4929–19 (Standard Test Method for Determination of Organic Chloride Content in Crude Oil). The oxygen-containing compounds were detected by GC-MS. The water contents of the feedstock and products were determined by Coulometric Karl Fischer titration.


**Conflict of interest**

The authors declare no conflict of interest.

*Assessment and Management of Pain in Palliative Care DOI: http://dx.doi.org/10.5772/intechopen.96676*

*Suggestions for Addressing Clinical and Non-Clinical Issues in Palliative Care*

pain is very subjective and will vary from patient to patient.

during the patient's palliative care stage.

The authors declare no conflict of interest.

**Acknowledgements**

**Conflict of interest**

assistance.

environmental and genetic factors. Differences in the site, the comprehension and pinpointing of the pain, the varied nature in intensity and the change in the same intensity due to previous/ongoing emotional turmoil, rendering the use of the same type of method for each obsolete. Many of the assessment tools are either disregarded or are still under heavy reviewing by peers. Some such as the IASP tool for assessment are unable to predict the future movement of pain symptoms and their debilitating effect. Though the ECS-CP, CPPS and ABPAT can predict to some extent they are not on par with the basic TNM staging of cancer. The intensity of the

The major problem of pain assessment is the subjective nature. The addition of emotional and psychological effects has been shown to produce more correlation between the subjective and the documented results and this will help in predicting the future pathway, the pain may take. Though this has been accomplished by the commonly accepted ECS-CP & CPPS but extensive review and research should be conducted such as in ABPAT with international validation (though it is still on-going). Also, assessment tools rather than being rigid can be multi-dimensional and include more domains specifically catering to the patient. This will not only provide a proper prognostic to the patient, but the caregiver will also be more prepared to administrate the required amount of analgesic /opioids to not only treat pain symptoms but also preventing any such overdosing of the drugs. And maybe increase the administration of drug alternatives that are not addictive such as non-opioids and nonsteroidal anti-inflammatory drugs. Hence, hopefully, this multi-dimensional pain assessment method might able to provide a smoother life

Sonika Charak is thankful to National Brain Research Centre for providing financial assistance. Chandra Mohan Srivastava and Manish Shandilya would like to acknowledge the support provided by Amity University Haryana for financial

**180**


**3. Experimental Support for the Above Concepts**

Figure 8 shows experimental threshold data under corrosion fatigue for steels with different heat treatments resulting in different yields stresses (from Usami [31]). Interestingly the change in the yield stress affects only the endurance limit but not long crack growth thresholds. Why this is so is not clear. With increasing yield stress, the material's behavior is increasingly elastic, as one should expect. Correspondingly, the internal stress triangle becomes smaller with increasing yield stress, indicating that the needed contribution from the local internal stress decreases. When the yield stress exceeds the fracture stress, the material becomes brittle. Figure 9 shows another example based on Hiroshi–Mura data [32] on stress corrosion of 4340 steel in H2(SO)4. The data are plotted in the form of the Kitagawa–Takahashi diagram. The endurance stress is similar to the minimum failure stress, σth, of a smooth specimen loaded in the corrosive environment. The mechanical equivalent of chemical internal stress is defined in the figure. The extent of experimental data on smooth and fracture mechanics specimens in corrosive media available in the open literature is limited. Nevertheless, the analysis shows that transition from short cracks to long cracks and the role of internal stresses in accentuating the crack initiation and growth process are general for all subcritical crack growth processes in materials.

**Figure 8.** Corrosion-fatigue crack growth in alloy steels with varying yield stress, from Usami, 1981.

**Figure 9.** Modified Kitagawa–Takahashi diagram for stress corrosion crack growth in 4340 steel in H2SO4 solution, extracted from Hiroshi–Mura data.

## *3.1. Application to Fracture Toughness*

The above concepts are relevant not only for subcritical crack growth, but also to fracture toughness (Figure 10). Experimental data from Bucci (1996; [33]) are shown in Figure 10a, and the data are plotted in terms of the modified Kitagawa–Takahashi diagram for two selected alloys (Figure 10b), one with low and the other with high fracture stresses. The horizontal portions of the plot correspond to the tensile fracture stress, while the inclined lines represent the K1C lines. The extension of the K1C lines defines the internal stresses needed to initiate a crack in a smooth specimen. The internal stress triangle is large for the low yield stress 2024-T3 alloy in comparison to the high yield stress 7075-T6 alloy, as expected.

**Figure 10.** Application to K1C, fracture data. (**a**) Experimental data from Bucci, 1996. (**b**) Representation of the data in terms of the modified Kitagawa–Takahashi diagram showing the internal stress triangle for the two cases, 7075-T6 and 2024-T3 Al-alloys.


*13.3.2. Fabricated TRD appliance construction*

TRD-type appliances are found to be effective in mild to moderate OSA treatment. They decrease AI, HI, AHI, oxygen desaturation, and excessive daytime sleepiness and increase minimum oxygen desaturation and genioglossus muscle activity. But the patient compliance is low with TRDs because of the irritation in the tongue, hypersalivation, uncomfortable feeling, and non-esthetic appearance.


*4.1.4 Other equipment*

The doctor's console, patient's console, and 3D endoscope camera system all need separate power supply. There is a backup battery on the patient console. In order to prevent emergencies, always connect the power supply to ensure that the backup battery is in full charge.

In the process of remote surgery, the patient's slave operation terminal and the doctor's console at the master operation terminal are connected through 5G network. The rest of the equipment is connected through the control signal line. Each time the remote surgery is performed, the labels at both ends of each cable need to be confirmed to ensure that the connection is correct.