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**Author details**

Zequan Xu

Department of Ophthalmology, First Medical Center, Chinese People's Liberation Army General Hospital (PLAGH), Beijing, P.R. China

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*Edited by Yunjin Yao*

Carbon-based photocatalysis has been considered as an economic, safe, renewable, and clean technology, for various applications. However, the pristine carbon material is usually restricted by unsatisfactory photocatalytic efficiency and practical applications due to the insufficient solar light absorption, the low-surface area, and the fast recombination of photogenerated electron-hole pairs. Various modification strategies, such as elemental and molecular doping, preparation of mesoporous carbon materials, and combination of conductive materials, are adopted to enhance the photocatalytic activity of carbon materials. In this book, we intend to describe the great potential of efficient and low-cost carbon-based materials in various realms, such as photodegradation of organic compounds, water splitting, and selective organic transformations.

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Visible-Light Photocatalysis of Carbon-Based Materials


**1.5. Apatite group minerals**

The apatite group includes minerals listed in **Table 3**. The most important are three minerals with ideal apatite formula Ca5(PO4)3F, Ca5(PO4)3OH and Ca5(PO4)3Cl known as fluorapatite, hydroxylapatite and chlorapatite, respectively. They are recently renamed as apatite–(CaF), apatite–(CaOH) and apatite–(CaCl). The origin of those three distinct names to denote the F− , OH− and Cl− variants and their distinction with respect to the "original apatite" *sensu lato* is uncertain [41],[45]. The composition and the cell dimension of major end members of apatite group minerals are listed in **Table 7**.

**Fig. 12.** Optical properties of fluoro-, hydroxyl- and chlorapatite series based on the values of end-member apatites [39].

Apatite is optically negative and normally uniaxial, although biaxial varieties with optic angle up to 20° are known. Carbonate bearing apatites (e.g. francolite), in particular way, have anomalous optics. Large variations in the composition within the apatite group make the accurate correlation of optical data difficult. The refractive index is the highest for chlorapa‐ tite (**Fig. 12**) and decreases by the substitutions of OH and F [39].

37 The distribution of atoms at cationic sites can be affected also by Coulombic effect as was recognized for the structure of mineral aiolosite (**Section 2.1.5**) and cesanite (**Section 2.1.7**).

**Table 7.** Composition and properties of calcium apatite end-member Ca5(PO4)3Z.

#### **1.5.1. Fluorapatite (Apatite–CaF))**

tory. Generally, **M**(1) sites (Wyckoff positions *4f* in P63/M structure, **Table 5**) are occupied by smaller cations (in particular Ca) and **M**(2) sites (Wyckoff positions *6h*) accommodate larger

24 Apatites and their Synthetic Analogues - Synthesis, Structure, Properties and Applications

The apatite group includes minerals listed in **Table 3**. The most important are three minerals with ideal apatite formula Ca5(PO4)3F, Ca5(PO4)3OH and Ca5(PO4)3Cl known as fluorapatite, hydroxylapatite and chlorapatite, respectively. They are recently renamed as apatite–(CaF), apatite–(CaOH) and apatite–(CaCl). The origin of those three distinct names to denote the F−

OH− and Cl− variants and their distinction with respect to the "original apatite" *sensu lato* is uncertain [41],[45]. The composition and the cell dimension of major end members of apatite

**Fig. 12.** Optical properties of fluoro-, hydroxyl- and chlorapatite series based on the values of end-member apatites

Apatite is optically negative and normally uniaxial, although biaxial varieties with optic angle up to 20° are known. Carbonate bearing apatites (e.g. francolite), in particular way, have anomalous optics. Large variations in the composition within the apatite group make the accurate correlation of optical data difficult. The refractive index is the highest for chlorapa‐

37 The distribution of atoms at cationic sites can be affected also by Coulombic effect as was recognized for the structure

tite (**Fig. 12**) and decreases by the substitutions of OH and F [39].

of mineral aiolosite (**Section 2.1.5**) and cesanite (**Section 2.1.7**).

,

cation37

[39].

such as Ba2+ or Pb2+ [45].

**1.5. Apatite group minerals**

group minerals are listed in **Table 7**.

Fluorapatite (Ca10(PO4)6F2, F-rich apatite, FAP and FAp) [45],[141] is the most common member in the group of apatite that can be found mainly in igneous rocks (fluorapatite is a common accessory mineral in syenites [39] and metamorphic environments, for example, in carbona‐

38 In some works termed as hydroxylapatite.

39 The symbol Ap, e.g. in HAp, reflects the abbreviation of mineral in rocks and ores, i.e. apatite = Ap.

40 Depends on the type of carbonated apatite (**Section 2.6**), **Table 7** provides data for Ca5(PO4,CO3)3OH (ideal composition of TYPE-B).

41 Apatite is known to be often nonstoichiometric, especially on the surface [41].

42 Measured/calculated density of mineral.

**Fig. 13.** Fluorapatite from (a) Cerro de Mercado Mine, Victoria de Durango, Mexico and (b) Sljudjanka, Bajkal, Russia.

tites and mica-pyroxenites [142]. The mineral crystallizes in the form of well-formed hexago‐ nal crystals elongated on [0001], forms tabularto discoidal crystals flattened on {0001} or occurs as granular, globular to reniform, nodular and massive. The properties and chemical compo‐ sition of fluorapatite mineral are listed in **Table 7**.

The color of fluorapatite mineral (**Fig. 13**) is pale green, green, light blue, yellow, purple, or white. Some varieties are colorless. Very brittle mineral gets broken to small fragments showing conchoidal fractures. Apatite shows poor cleavage on {0001} and {101 ¯1}. Fluorapa‐ tite is the most insoluble from the phosphate minerals [143],[144]. Apatite forms rare contact twins on {112 ¯1} or {101 ¯3}. Some examples of fluorapatite crystals morphology are introduced in **Fig. 14**.

**Fig. 14.** Habit of fluorapatite crystals.

As was mentioned above (**Section 1.2**), fluorapatite was the first apatite with established structure [107],[108]. There is slight disagreement on the position of fluoride anion [145] Fluorapatite crystallizes in hexagonal dipyramidal crystal system with the parameters listed in **Table 7**. Atomic parameters including the number of atoms (*N*, where Σ*N* = 42) with equivalent site symmetry, their positions (coordinates *x*, *y* and *z*) in fractional coordinate system and equivalent isotropic temperature factor (*B*) for fluorapatite by HUGHES et al [33] are listed in **Table 8**.

**Table 8.** Positional parameters and equivalent isotropic factor for fluorapatite [33],[148].

## The lengths of bonds in the fluorapatite structure are listed in **Table 9**.

**Table 9.** Bond lengths in the structure of fluorapatite [33].

tites and mica-pyroxenites [142]. The mineral crystallizes in the form of well-formed hexago‐ nal crystals elongated on [0001], forms tabularto discoidal crystals flattened on {0001} or occurs as granular, globular to reniform, nodular and massive. The properties and chemical compo‐

**Fig. 13.** Fluorapatite from (a) Cerro de Mercado Mine, Victoria de Durango, Mexico and (b) Sljudjanka, Bajkal, Russia.

The color of fluorapatite mineral (**Fig. 13**) is pale green, green, light blue, yellow, purple, or white. Some varieties are colorless. Very brittle mineral gets broken to small fragments

tite is the most insoluble from the phosphate minerals [143],[144]. Apatite forms rare contact

As was mentioned above (**Section 1.2**), fluorapatite was the first apatite with established structure [107],[108]. There is slight disagreement on the position of fluoride anion [145] Fluorapatite crystallizes in hexagonal dipyramidal crystal system with the parameters listed in **Table 7**. Atomic parameters including the number of atoms (*N*, where Σ*N* = 42) with equivalent site symmetry, their positions (coordinates *x*, *y* and *z*) in fractional coordinate system and equivalent isotropic temperature factor (*B*) for fluorapatite by HUGHES et al [33] are

**Atom** *N* **Site symmetry** *x y z B* **[Å2**

Ca(1) 4 C3h 2/3 1/3 0.0010 0.91 Ca(2) 6 C3 -0.00712 0.24227 ¼ 0.77 P 6 Cs 0.36895 0.39850 ¼ 0.57

¯3}. Some examples of fluorapatite crystals morphology are introduced

¯1}. Fluorapa‐

**]**

showing conchoidal fractures. Apatite shows poor cleavage on {0001} and {101

sition of fluorapatite mineral are listed in **Table 7**.

26 Apatites and their Synthetic Analogues - Synthesis, Structure, Properties and Applications

¯1} or {101

**Fig. 14.** Habit of fluorapatite crystals.

listed in **Table 8**.

twins on {112

in **Fig. 14**.

**Fig. 15.** Primitive unit cell of fluorapatite (C10(PO4)6F2) with atoms labeled according to symmetric type of element (a). The crystal structure of apatite (b, perspective view along the *c*-axis) and structure of columns (c, d).

The hexagonal crystal structure of fluorapatite of P63/M space group is shown in **Fig. 15**. The atoms of Ca occupy two distinct sites [146], [147]:

**i.** Ca(I)O9 polyhedra in sevenfold coordination


**1. Introduction**

The ancient temple heritage space is one subcategory of integrated spaces with profound religious architecture, culture, and landscape, which is vital for cultural redevelopment, especially in East Asian countries. With the change and development over thousands of years, the spatial layouts and functionalities of temples in East Asia have been gradually transformed, while many temples have been destroyed or even disappeared due to certain causes, e.g., wartime destruction, lack of maintenance costs, and inappropriate techniques in conservation practices. Spatial planning, planting design, and natural aesthetic values are all the main factors that can affect the conservation and revitalization of ancient temples [1]. Cognitive mechanisms and the characteristics of isomorphic synaesthesia in ancient Chinese temples are also primarily analyzed by some researchers [2]. In recent years, there have been some studies focusing on quantitative estimation for the conservation and management of ancient temples and visitors' sensory perceptions of heritage. Six dimensions in ancient building spaces, i.e., "adoration", " nostalgia', 'liveliness', 'exquisiteness', 'hedonic value', and 'placeness' on visitors' aesthetic experiences are estimated by quantitative methods [3]. A netnographic approach for conducting narrative analysis on heritage

**Citation:** Zhou, K.; Wu, W.; Dai, X.; Li, T. Quantitative Estimation of the Internal Spatio–Temporal Characteristics of Ancient Temple Heritage Space with Space Syntax Models: A Case Study of Daming Temple. *Buildings* **2023**, *13*, 1345. https://doi.org/10.3390/ buildings13051345

Academic Editors: Lucia Della Spina, Maria Rosa Valluzzi, Antonia Russo, Paola Pellegrini and Angela Viglianisi

Received: 27 March 2023 Revised: 16 May 2023 Accepted: 19 May 2023 Published: 21 May 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

tourism marketing is also put forward [4]. An information model of Chinese traditional garden heritage spaces is constructed to improve the accuracy of spatial information and management efficiency, which provides a more convenient solution for the conservation, redesign, and management of temple heritages [5].

Space syntax is a spatial topology algorithm developed by Bill Hillier to estimate and explain the correspondence between spatial form and function quantitatively [6]. The space syntax theory has been widely applied in interdisciplinary space-related fields, which is also applicable to the quantitative spatial estimation for heritage spaces [7]. Space syntax theory suggests that the core of spatial characteristics is the 'association' between spaces [8]. In the spatial configuration system, each geological factor is constrained by the other, and there is a complex internal topological relationship between each element [9]. 'Angular segment analysis' (ASA) and 'visibility graph analysis' (VGA) are two typical space syntax models that have been widely applied in most research, by which complex characteristics of the space are simplified and processed as a grid-based topological system consisting by interconnected constraints [10].

Both ASA and VGA models are effective in representing the spatial configuration changes and the influences by human beings on the space, visualized in a visual graphical language [11]. In the recent decade, spatial syntax has been applied to the study of multiple types of buildings and landscapes, especially been utilized as a convincing tool to assess the spatial organization of cultural heritage sites [12]. Spatial Differences among several typical ancient heritage palaces are compared by multiple space syntax models to guide restoration planning projects for those heritage redevelopment projects, especially for redesigning visitors' routes through the temple heritage [13]. The ASA and VGA models are also applied to estimate the spatial configuration in the case study of temple heritage, e.g., the Canaanite temples, which indicates that the temple heritage spaces are unique in their characteristics, not only in the role they play in the surrounding landscape and region but also in their distinction from the surrounding ancient temple heritage spaces [14].

Space syntax models have also been introduced into some reliable studies related to ancient temples in East Asia. Using spatial syntax modeling, the spatial structure of the Chinese building heritage has been revealed [15]. For instance, the Lion Grove Garden Temple heritage spaces in Suzhou City are estimated based on space syntax theory and found that spatial visual features affect the spatio–temporal distribution of visitors [16]. A space syntax-based analysis method has been developed to assist in improving tourists' spatial cognition in Chinese historic districts for urban designers and landscape architects [17].

However, there are still a few cases of space syntax in space, while the spatio–temporal structural evolution of ancient temples has not been learned thoroughly. Therefore, quantitative estimation by space syntax models is of high potential in the estimation of internal spatio–temporal characteristics of ancient temples, which can offer necessary guidance for the conservation, redesign, reactivation, and redevelopment of similar spaces.

#### **2. Materials and Methods**

#### *2.1. Study Site*

Daming Temple (119.41◦ E, 32.42◦ N) is one of the eight famous monasteries in Yangzhou City, China, which was built during 457–464 A.D. Monk Jianzhen (688–763 A.D., also known as 'Ganjin' in Japanese), the host of the Daming Temple, had once traveled eastward to Japan and built the Tosh ¯ odai-ji Temple, which significantly accelerated the ¯ communication of Mahayana Buddhism culture between China and Japan. Daming Temple has been expanded several times. In the Sui Dynasty, Emperor Yang Jian built the Qiling Pagoda in Daming Temple. During the Northern Song Dynasty, some literati contributed to the design and construction of the temple, e.g., the literatus Ouyang Xiu (1007–1072 A.D.) designed the residence Pingshan Hall in the temple; Su Shi (1037–1101 A.D.), the wellknown writer, calligrapher, and painter, designed and constructed the residence Guling Hall next to Pingshan Hall. During the reign of Qianlong (1736–1796 A.D.) in the Qing Dynasty, Wang Yinggeng (1680–1742 A.D.), a well-known merchant, built the West Garden in

the temple, which was praised by Emperor Qianlong for its scenery. Referring to historical records and ancient literature [18], there was no noticeable change in the spatial layout of the Daming Temple from the end of the Qing Dynasty to 1962. From 1962 to 1973, Jianzhen Memorial Hall by the temple was designed and constructed, which dramatically affected the spatial layouts of the temple garden. After the 1990s, Daming Temple expanded the East District and the West Garden while changes in its spatial layout occurred. Since the 1990s, the financial revenue of the temple has been increasing rapidly for the redevelopment of tourism; thus, the temple's income has been able to cover the large-scale maintenance since the 2010s.

Daming Temple (Figure 1) is a typical representative of a re-activated Buddhism temple in China, which has undergone long-term alterations and expansions. There is an urgent need to study the building space of the Damien Monastery in order to advocate for the conservation and redevelopment of the temple's heritage. Historical maps of 3 periods of Daming Temple were selected respectively, considering the changes in new-built areas, i.e., the construction of Jianzhen Memorial Hall and the expansion of the East District since the 2000s.

**Figure 1.** Two-dimensional map of spaces in the Daming Temple during different periods.

#### *2.2. Methods of Quantitative Estimation*

In the space syntax theory, the spatial structure analysis should focus on the 'spatial configuration', i.e., a set of complex relationships between spaces, all of which are interrelated in a global spatial structure. Spatial configuration can be visualized quantitatively by typical models, i.e., angular segment analysis (ASA), visibility graph analysis (VGA), and agent-based analysis (ABA). These models can reveal the comparability of measures of spatial configuration between different periods of space. The ASA model uses 'angular distance' rather than 'metric distance'. The 'angular distance' can represent the visitors' psychological and cognitive distance, such as the psychological distance expectation when

they pass the steps. The visibility graph analysis (VGA) model in the space syntax system has also been widely adopted in small-and medium-scale spatial studies. As the temple heritage space has been redesigned several times, the structure of the space has changed accordingly. It is, therefore, necessary to visualize the spatial changes quantitatively. In typical Asian temple spaces, the levels of visibility and accessibility are often out of alignment, which can only be represented in the VGA model rather than the ASA model. Therefore, the study involves some parameters and indices in 2 space syntax models mentioned above, which are introduced as follows.

Some indices are commonly used in the ASA and VGA model, including 'Mean depth' (MD), normalized angle integration (NAIN), normalized angle choice (NACH) [19], and connectivity. In the space syntax system, 'depth' is the selected from the system or the amount of space passed through a given starting point. The MD value of a system is the average of all possible steps from a given starting point [20]. Angular segment integration (int.) shows how well each segment is integrated with all other segments, i.e., the total number of directional changes [21]. Angular choice shows the degree of integration of each segment of the path in terms of the lowest total number of angular deviations compared to all other segments. The angular choice analysis shows the potential for through movement in the spatial system [22].

Visual graph analysis (VGA) is a method for evaluating the inter-visibility of spaces. It builds upon the logic of an isovist analysis; it is different in that a visual graph analysis is derived from all the roots of each isovist field from each cell on a given raster. The VGA is applied at eye level (what people can see) and at knee level (where people can move) [23].

In both the ASA and VGA models, the value of connectivity is determined by the number of knots connected to the knot [24], calculated by Formula (1).

$$MD\_i = \frac{\sum\_{j=1}^{n} d\_{ij}}{n-1}, i \neq j \tag{1}$$

where *n*—amount of knot in the system; *dij*—the shortest topological distance between any two points.

The MD value in the VGA model can also be further converted to obtain an 'integration' index. The MD metric is often utilized to express the spatial configuration quantitatively. The 'Connectivity' (con.) index is a static local measure and explains the number of connections that each segment has to its direct neighboring ones. The 'Mean connectivity' (mean con.) index is defined as the average of the connection values of all nodes in the global space [25].

In the ASA model, NACH and NAIN are also adopted in accordance with methods put forward by Hiller et al. [26]. The values of NAIN and NACH can be calculated by Formulas (2) and (3).

$$NAIN\_i = n^{1.2} / \sum\_{j=1}^{n-1} d(i-j) \, ; i \neq j \tag{2}$$

$$NACH\_i = \frac{\log(\sigma\_{s,t}(i) / \sigma\_{s,t} + 1)}{\log\left(\sum\_{j=1}^n d(i,j) + 3\right)}, i \neq j \tag{3}$$

where *n* is the total knot amount; *d* is the shortest distance between point *i* and point *j*.

The 'Intelligibility' index is an indicator of the correlation between the local and the whole in a spatial system. Relevant empirical studies [26] have shown that the intelligibility of space is higher, and visitors will not easily get lost in space, and vice versa. The 'Intelligibility' index can be calculated by the Formula (4).

$$R^2 = \frac{\left[\sum \left(\mathbb{C}\_i - \overline{\mathbb{C}}\right) \left(I\_i - \overline{I}\right)\right]^2}{\sum \left(\mathbb{C}\_i - \overline{\mathbb{C}}\right)^2 \sum \left(I\_i - \overline{I}\right)^2}, \text{ i } \neq j \tag{4}$$

where *C* is the mean of all cell space connectivity values; *I* is the mean of all cell space global integrations.

'Configurational centrality' in spatial syntax is a concept used to describe the degree to which a particular location in a built environment is centrally located in relation to other locations within that environment. It is based on the idea that the spatial layout may affect the way visitors move through spaces [27,28].


**DECISION SUPPORT SYSTEMS**

Edited by **Chiang Jao**

#### **Decision Support Systems**

http://dx.doi.org/10.5772/3371 Edited by Chiang Jao

#### **Contributors**

Thomas M Hemmerling, Kaya Kuru, Yusuf Tunca, Ramdane Hedjar, Victor E Cabrera, Po-Hsun Cheng, Heng-Shuen Chen, Hsin-Ciang Chang, Wen-Chen Chiang, Gabriela Prelipcean, Mircea Boscoianu, María Teresa Lamelas, Oswald Marinoni, Juan de la Riva, Andreas Hoppe, Edward Lusk, Monica Adya, Luciene Delazari, Leo Van Raamsdonk, Christine Chan

#### **© The Editor(s) and the Author(s) 2012**

The moral rights of the and the author(s) have been asserted.

All rights to the book as a whole are reserved by INTECH. The book as a whole (compilation) cannot be reproduced, distributed or used for commercial or non-commercial purposes without INTECH's written permission. Enquiries concerning the use of the book should be directed to INTECH rights and permissions department (permissions@intechopen.com).

Violations are liable to prosecution under the governing Copyright Law.

Individual chapters of this publication are distributed under the terms of the Creative Commons Attribution 3.0 Unported License which permits commercial use, distribution and reproduction of the individual chapters, provided the original author(s) and source publication are appropriately acknowledged. If so indicated, certain images may not be included under the Creative Commons license. In such cases users will need to obtain permission from the license holder to reproduce the material. More details and guidelines concerning content reuse and adaptation can be foundat http://www.intechopen.com/copyright-policy.html.

#### **Notice**

Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book.

First published in Croatia, 2012 by INTECH d.o.o. eBook (PDF) Published by IN TECH d.o.o. Place and year of publication of eBook (PDF): Rijeka, 2019. IntechOpen is the global imprint of IN TECH d.o.o. Printed in Croatia

Legal deposit, Croatia: National and University Library in Zagreb

Additional hard and PDF copies can be obtained from<EMAIL_ADDRESS>
Decision Support Systems Edited by Chiang Jao p. cm. ISBN 978-953-51-0799-6 eBook (PDF) ISBN 978-953-51-5713-7


*2.5. Color Evaluation*

The color of the mayonnaise was evaluated with a CHROMA METER CR5 instrument (Konica Minolta, Osaka, Japan), illuminant D65; each sample was homogeneously distributed into a glass vessel and the color was recorded at five different points. The average of the five measurements was assessed for all the colorimetric parameters (L\*, *a\**, and *b\**). In the CIE Lab colour space, L\* represents the lightness within the range of 0 (black) to 100 (white); *a\** is the redness, from green (−*a\**) to red (+*a\**); and *b\** is the yellowness, from blue (−*b\**) to yellow (+*b\**). The *a\** and *b\** parameters were used to calculate the tonality angle (Hue angle, *h*◦) according to Equation (1):

$$h^\circ = \tan^{-1} \left(\frac{b^\*}{a^\*}\right) \tag{1}$$


**4. Discussion**

**Treatment**

**Group IV**

**Group V**

**Group VI**

**Group VII**

**Group VIII**

**Treatment**

**Group IV**

**Group V**

**Group VI**

**Group VII**

**Group VIII**

**ANOVA F**

**SOD Catalase**

44±2.432 33.3± 1.840\* 42.02± 2.322 59.67± 3.298 (19.52%) (36.53%) (31.11%) (45.95%)

45.6±2.520 35.9± 1.984\* 42.5± 2.349 59.97± 3.315 (24.35%) (47.19%) (34.92%) (47.51%)

55±3.040\* 41.15± 2.274\* 44.05± 2.435 61.96± 3.425\* (52.68%) (68.71%) (47.22%) (57.82%)

60.9±3.366\* 43.13± 2.384\* 45.2± 2.498 62.1± 3.432\* (70.46%) (76.83%) (56.34%) (58.54%)

68±3.759\* 41.83± 2.312\* 50.6± 2.775\* 62.57± 3.458\* (91.86%) (71.50%) (96.03%) (58.54%)

> **ATPase Liver ATPase Kidney (mgPi/100gm/min)**

1721.4± 95.16\* 1814.28±100.29 (60.71%) (4.30%)

1864.28±103.06\* 1907.14±105.43 (83.02%) (18.28%)

1889±104.43\* 2042.85±112.93 (87.09%) (38.71%)

1966.06±108.69\* 2149.99±118.85\* (99.22%) (54.83%)

1969±108.85\* 2107.14 ±116.48 (99.68%) (48.38%)

**Value 22.664@ 12.569@ 4.464@ 2.911@**

Data are mean ± S.E., n=6.ANOVA (F Values at 5% level).# P≤0.05 vs. Control,\*P ≤0.05 vs. ATD,@ Significant

**Group I** 1971±108.95 2449.99±135.44 **Group II** 2114±116.86 2257.14±124.77 **Group III** 1335.71±73.84# 1785.7±98.72#

**ANOVA F Value 6.350@ 4.696@** Data are mean ± S.E., n=6.ANOVA (F Values at 5% level). # P≤0.05 vs. Control,\*P ≤0.05 vs. ATD, @ Significant.

**Table 6.** Therapeutic Effect of *P.amarus* on ATPase against ATD

**Table 5.** Effect of *P.amarus* on SOD, Catalase activity in liver and kidney against anti TB drugs.

**Group I** 70.7±3.908 48.78± 2.696 50.7± 2.802 70.1± 3.875 **Group II** 76±4.201 51.2± 2.830 51.8±2.863 62.14± 3.435 **Group III** 37.52±2.074# 24.39±1.348# 38.1± 2.106# 50.8± 2.808#

288 Pharmacology and Nutritional Intervention in the Treatment of Disease

**(U/min./mg protein) (µ mole of H2O2 oxidised/min/mg protein) Liver Kidney Liver Kidney**

The liver diseases remain one of the serious health problems as variedly exposed to xenobiotics. Modern medicines have little to offer for alleviation of hepatic diseases. Although *P. amarus is* reported to possess varied medicinal properties such as antiviral, anticancer, antioxidant, anti-inflammatory, hepatoprotective (Joshi and Parle, 2007), there is no previous report about the hepatoprotective activity of this plant against anti TB drugs. The present investigation reports the hepatoprotective effect of *P.amarus*. In the present study, hepatotoxicity model in albino rats was successfully produced by administering RIF, INH and PZA.

Effects of administration of Anti TB Drugs and *Phyllanthus amarus* orally on selected biochem‐ ical parameters in rat tissue and blood serum is presented in Table 1-6.

Significant rise above the normal upper limits in the measured serum transaminases in toxicant group on day 60 of the experiment was a biochemical indication of liver injury. Elevated levels of serum enzymes, AST and ALT are indicative of cellular leakage, and loss of functional integrity of cell membrane in liver (Ranawat *et al.,* 2010). Oral administration of *P. amarus* extract at doses (100, 200, 300 and 400 mg/kg) showed significant recoupment in a dose dependent manner (P ≤0.05) (Table1).

The increased level of serum alkaline phosphatase is reliable marker of liver damage, which occurs due to the *de novo* synthesis by the liver cells (Muriel and Escobar, 2003). Serum albumin concentration is affected by hepatic protein and its synthesis is a typical function of normal liver cells (Thirunavukkarasu and Skthisenkaran, 2003). Bilirubin is one of the most frequent clinical test to evaluate the extent of chemically induced hepatotoxicity (Zimmerman, 1973). Toxicants administration caused significant increase in the serum alkaline phosphatase activity. Stabilization of SALP and bilirubin levels by the treatment of *P.amarus* is clear indication of improvement in functional status of liver cells. Results suggested that *P.amarus* at a dose of 400mg/kg, b.w., have protective effect on plasma membrane of hepatocytes. (Table2)

As a measure of renal function status, serum urea, uric acid and creatinine are often regarded as reliable markers (Adebisi *et al*., 2000). Serum creatinine has been used to estimate glomerular filtration rate. Thus, elevations in the serum concentrations of these markers are indicative of renal injury (Adebisi *et al*., 2000; Adewole *et al.,* 2007).The same was observed after toxicant administration. It may be due to dysfunctional and dystrophic changes in the liver and kidney. Experiment has shown that *P.amarus* at different doses, showed significant protective but the highest protection was obsereved at 300 and 400 mg/kg with mere difference indicating normal glomerular filtration rate thereby improved functional status of kidney. (Table 3)

Various biochemical parameters were measured in liver and kidney tissues. The levels of TBARS in liver and kidney tissues of ATD intoxicated rats were significantly elevated when compared to the level of TBARS in control animals. The increased lipid peroxidation results in changes in cellular metabolism of the hepatic and extra hepatic tissues, which ultimately leads to the whole cell deformity and cell death (Arun and Balasubramanian, 2011). The administration of herbal drug *P. amarus* at the different therapeutic doses showed reduction in TBARS level. The standard hepatoprotective drug Silymarin maintained the decreased lipid peroxidation level to the normal limits in the liver.

major parameters showed percent protection level above 50% at dose levels 300 and 400mg/kg. All these properties make *P. amarus*, a novel herb for treating oxidative stress and anti Tb drug associated hepatic toxicity. There is, however, the need of further experiments

Hepatoprotective effect of *Phyllanthus amarus*

http://dx.doi.org/10.5772/57373

291

for chronic study to exercise on excessive and prolonged use of this plant.

**Figure 1.** Hepatocytes of the normal control group showed a normal lobular architecture of the liver (400 x).

**Figure 2.** Hepatocytes of the INH + RIF+ PZA treated group showed liver cell necrosis and inflammation also observed

in the centrilobular region with portal triaditis (400 x).

**6. Histopathological studies**

Concomitant cellular oxidative stress was manifested by reduced GSH levels and in‐ creased lipid peroxidation. The inverse linear relationship between the ROS level and the GSH level indicated that free radical species were generated by exposure to anti TB drugs which reduced intracellular antioxidant levels. The results indicate that, the herbal drug *Phyllanthus amarus* has very good hepatoprotective effect in liver damage. The results were presented in the Table 4.

Superoxide dismutase and Catalase mutually function as important enzymes in elimination of Reactive oxygen species (ROS). SOD is the major attractive metalloprotein in the antioxidant family. The defensive antioxidant enzyme next to SOD is CAT. CAT is an enzymatic antioxi‐ dant widely distributed in all animal tissues, and the highest activity is found in the red cells and liver. Both are the key component of the antioxidant defense system. In the present study, the observed decrease in SOD and CAT activities were presumably associated with the increased oxidative stress caused by these toxicants that might be due to low level of zinc (a metal constituent of the enzyme SOD) in liver tissue (Arun and Balasubramanian, 2011) Therapy at 200-400 mg/kg b.w. reversed the SOD and CAT activity in the liver tissues and protected from free radical induced oxidative stress. These observations are substantiated by author (Gnanadesigan *et al.,* 2011).(Table 5)

ATPase is a membrane bound enzyme. Since, phosphatase is a constituent of all the body tissues; it plays an important role in inorganic pyrophosphates activity. ATPase activity may be considered as a marker for assessing hepatocellular damage induced by hepatotoxic agents. (Table 6)

In our experiment, a concurrent fall was found in ATPase in liver after toxicants exposure. It might be due to dysfunctional and dystrophic changes in the mitochondria and cell membrane permeability. This damage was also very clearly visible in histopathological studies after toxicant administration. These observations are substantiated by other authors (Gao and Zhou, 2005; Krithika and Verma, 2009).The effect of the extracts on ATPase was as pronounced with 100mg/kg as with 200-400mg/kg b.w.

Liver damage induced by toxicant was associated with a variety of biochemical abnormalities following loss of integrity of the cell membrane or interference with normal hepatocytes metabolism and function.

The reason for hepatoprotective effect of the extracts may be due to presence of lignans and flavonoids which might have scavenged the free radical offering hepato protection.


New Advances in the Mechanisms and Treatment of Melanoma

**91**

**Chapter 6**

Session

**Abstract**

*and Jekaterina Erenpreisa*

genes are expressed in all three tissue cohorts.

DSB hot spots, ancestral meiosis

**1. Introduction**

The Role of the Meiotic

Component in Reproduction of

*Dace Pjanova, Ninel M. Vainshelbaum, Kristine Salmina*

The ectopic expression of cancer testis (CT) antigens and classic meiotic genes is characteristic and a hallmark of poor prognosis of melanoma disease. Here the potential mechanisms of meiotic influence on the cell and life cycle of malignant melanoma are reviewed in the genetic, epigenetic, and evolutionary aspects. The involved mutant B-RAF and N-RAS-induced senescence may be reversed by reprogramming, with stemness linked to meiotic landscape, possibly induced by DNA double-strand breaks at the mutual telomere hot spots. The induced by senescence mitotic slippage (reset of interphase from arrested metaphase) and resulting polyploidy trigger the meiotic ploidy cycle to function for effective DNA recombination repair, genome reduction, and escape of survivors, which enter the mitotic cycle again. The aberrant meiotic pathway in cancer is reviewed in the ancestral asexual variants; inverted meiosis is possible. The conundrum of cancer aneuploidy paradox, selection of fit clones, and the Muller's Ratchet of inevitable accumulation of harmful mutations is discussed. The bioinformatic study of the densely connected protein interaction network of CT antigen expressed genes revealed the melanomagenesis attractor composed of PRAME and small MAGEA group in primary tumors as compared with B-RAF-mutant nevi, restructured stemness network; invasive melanoma further displays the leading role of SPANX CT antigen group; meiotic

**Keywords:** B-RAF-mutant melanoma, reversible senescence, reversible polyploidy,

Approximately 50% of melanomas carry mutations in the gene encoding *B-RAF* [1]. Ninety percent of activating *B-RAF* mutations affect the codon 600 and the most common missense change there is V600E [2]. This mutation leads to a constitutive activation of B-RAF, and consequently of the MAPK/ERK pathway,

B-RAF-Mutated Melanoma: A

Review and "Brainstorming"


**Reproduction**

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[147] Pape LA, Price JM, Alpert JS, Ockene IS, Weiner BH: Relation of left atrial size to pul

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#### **Abnormalities in the Sexual Cycle of Bitches Abnormalities in the Sexual Cycle of Bitches**

Ali Risvanli, Halis Ocal and Cahit Kalkan Ali Risvanli, Halis Ocal and Cahit Kalkan

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64648

#### **Abstract**

Sexual-cycle abnormalities are an important cause of infertility in bitches, with disorders such as anestrus, split estrus, and persistent estrus having varied etiologies. Sexual-cycle abnormalities in bitches may be addressed as follicular- or luteal-phase disorders. However, pet owners should have a good working knowledge of the sexual cycles of their animals in order to better understand these disorders.


**1. Introduction**

Nowadays, the problem of increasing reliability of manufacturing process, which represents the core of any industrial enterprise, affects the realization of business goals so that it is an interesting field of research for both researchers and practitioners. According to the results of the best practice, and literature sources [1], it can be said that failures have the greatest impact on the reliability of the manufacturing process. Although there is a significant number of production and organization concepts, such as world class manufacturing (WCM), just-in-time (JIT), the scope of this paper is set to the lean manufacturing and in compliance with that, failures leading to lean waste are identified. According to the lean concept [2], there are seven types of waste found in any process: transportation, inventory, motion, waiting, overprocessing, overproduction, and defect. Later, Liker [3] introduced waste related to underutilization of labor creativity, and it is denoted as Unused employee creativity. Reducing or eliminating the impact of identified failures can be performed by implementing various quality methods.

Quality methods are extremely important, because without reliable and complete information, it is practically impossible to undertake effective measures aimed at improving manufacturing processes [4,5].

There are many quality methods that are defined in the literature [6,7]. Application of these quality methods can lead to the simultaneous elimination or reduction of the

**Citation:** Gojkovi´c, R.; Ðuri´c, G.; Tadi´c, D.; Nesti´c, S.; Aleksi´c, A. Evaluation and Selection of the Quality Methods for Manufacturing Process Reliability Improvement—Intuitionistic Fuzzy Sets and Genetic Algorithm Approach. *Mathematics* **2021**, *9*, 1531. https://doi.org/10.3390/ math9131531

Academic Editors: Jorge de Andres Sanchez and Laura González-Vila Puchades

Received: 29 May 2021 Accepted: 24 June 2021 Published: 29 June 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

impact of one or more identified failures of the manufacturing process. Respecting the limited resources (money, time, etc.), it can be concluded that it is almost impossible to implement a number of quality methods at the same time. In practice, the basic task of the reliability manager is how to choose a set of quality methods whose application of the considered problem can be effectively solved in the shortest possible time. Many authors suggest that the choice of quality methods should be based on the priority of failures [8–11]. Experiences of best practice show that decision makers (DMs), when choosing quality methods, respect many criteria besides the priority of failures. In this research, the authors suggest that in determining the set of quality methods, besides the mentioned, it is necessary to consider applicability of methods and implementation costs due to limited financial resources of small and medium enterprises in the manufacturing industry. Prioritization can be seen as a problem in itself. According to [12], the priority assessment under an uncertain environment is based on the failure mode and effect analysis (FMEA) which is combined with fuzzy sets theory [13], as in this research. In other words, evaluation of failures is performed by respecting to risk factors (RFs): severity, occurrence, and detection. According to suggestions of Liu [14], in this research, assumptions were introduced: (i) RFs have not equal the relative importance, and (ii) the relative importance of RFs and their values can be adequately described in linguistic terms, and (iii) the priority of failures is based on the rank of risk priority number (RPN) which is calculated as the product of these three RFs with respects to their weights.

Respecting the nature of human thinking, it can be said that DMs hardly give an accurate evaluation of uncertain data in practical decision problems. Hence, DMs express their assessments easier when using natural language words instead of the precise numbers. The development of theories of mathematics, such as the theory of intuitive fuzzy sets (IFSs) [15] allows vagueness to be represented fairly quantitatively. The advantages of using IFSs are: (1) transient stages during decision making can be rendered by intuitionistic indices, and (2) it is possible to foresee the best and worst results.

As it is known, in the manufacturing process management literature, it is almost impossible to find papers where the problem of choosing the quality methods set is considered as a combinatorial optimization problem. Since, in this research, the treated problem is stated as a rubber knapsack problem which represents the version of the classic 0–1 knapsack problem (0–1 KP) with the goal of finding, in a set of items of given values and weights, the subset of items with the highest total value, subject to a total weight constraint [16,17]. This can be marked as one of this paper's novelties. Finding the optimal solution of the considered problem is based on using the genetic algorithm (GA) [18]. By using GAs, perform a search in complex, and large landscapes, and provide near-optimal solutions for objective function an optimization problem. In the literature, GA is a widely used metaheuristic method for solving difficult nondeterministic polynomial time (NP) problems from different domains [19–21], as in this research.

Motivation for this research comes from the fact that there are almost no literature sources that treat the selection of quality methods where uncertainties are given by exact ways.

The wider objective of this research may be interpreted as: (1) identification of failures in manufacturing process in SMEs of the process industry, (2) assessment identified failures based on FMEA, (3) modelling of the existing uncertainties are performed by using triangular intuitionistic fuzzy number (TIFN) [22,23], (4) the priority of failure is determined by applying the RPN with TIFNs with respects to RF weights, (6) selection of quality methods is stated as KP, and obtaining an adequate set of quality methods is based on the application of GA. The authors believe that the solution obtained in this way is significantly less burdened by the subjective attitudes of DMs, and therefore the effectiveness of solving the problem of reliability of the manufacturing process is significantly better.

The paper is organized in the following way: In Section 2, there is a literature review. Methodology is presented in Section 3. The proposed Algorithm is presented in Section 4. The case study is presented in Section 5. Conclusion and discussion are given in Section 6.